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Springer Series in Biophysics 23
Jiapu Zhang
Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures Research on COVID- 19
Springer Series in Biophysics Volume 23
Series Editor Boris Martinac, Molecular Cardiology & Biophysics, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia
The “Springer Series in Biophysics” spans all areas of modern biophysics, such as molecular, membrane, cellular or single molecule biophysics. More than that, it is one of the few series of its kind to present biophysical research material from a biological perspective. All postgraduates, researchers and scientists working in biophysical research will benefit from the comprehensive and timely volumes of this well-structured series.
Jiapu Zhang
Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures Research on COVID- 19
Jiapu Zhang Institute of Innovation, Science and Sustainability (IISS), School of IT and Applied Mathematics, Sciences and Engineering Federation University Ballarat, VIC, Australia
ISSN 0932-2353 ISSN 1868-2561 (electronic) Springer Series in Biophysics ISBN 978-3-031-36772-4 ISBN 978-3-031-36773-1 (eBook) https://doi.org/10.1007/978-3-031-36773-1 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Paper in this product is recyclable.
Dedicate to my mother Xian’ai LIU
Preface
Let us first briefly introduce the three classes of proteins of SARS-CoV-2: the structural proteins (SPs), the non-structural proteins (NSPs), and the accessory proteins (APs). Coronaviruses (CoVs) are viruses with a spherical positive single-stranded RNA envelope assigned to .α, β, γ , and .δ genera. SARS-CoV-2 of COVID-19 belongs to the .β genus. SARS-CoV-2 has a positive viral RNA genome expressing open reading frames (ORFs) that code for 4 SPs, 16 NSPs, and about 7 accessory proteins (ORF1a, ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, ORF9b, ORF9c, and ORF10). The four SPs of .β-CoV are envelope protein (E-protein), membrane glycoprotein (M-protein), nucleocapsid phosphoprotein (N-protein), and spike glycoprotein (S-protein), and mediation of coronavirus host infection is established by S-protein, where S-protein has a Receptor-Binding Domain (RBD) S1 that mediates the binding to host cell receptor, the Angiotensin Converting Enzyme 2 (ACE2), while the S2 subunit of S-protein promotes membrane fusion. The SPs are bound to the RNA in the N-protein or to the lipid bilayer membrane of the viral envelope, where the lipid bilayer proteins include the E-protein, Mprotein, and S-protein. The N-protein is composed of a serine-rich linker region sandwiched between N-Terminal Domain (NTD) and C-Terminal Domain (CTD); these terminals play a role in viral entry and its processing post entry. The NTD forms orthorhombic crystals and binds to the viral genome. The linker region contains phosphorylation sites that regulate its functioning. The CTD promotes nucleocapsid formation. The E-protein contains an NTD, hydrophobic domain, and CTD which form viroporins needed for viral assembly. The M-protein possesses hydrophilic C-terminal and amphipathic N-terminal; its long-form promotes spike incorporations and the interaction with E facilitates virion production. SPs are encoded within the 3’ end of the genome. During COVID-19, there appears variants of SPs. Among the SPs, S-protein and N-protein accumulated a larger number of mutations whereas E- and M-proteins are mostly conserved. In terms of mutational changes, E- and M-proteins are relatively more stable than N- and S-proteins. Several co-occurrence substitutions are observed, particularly in S- and N-proteins. Substitution specific to active sub-domains reveals that heptapeptide repeat, fusion peptides, transmembrane in Svii
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protein, and NTD and CTD in N-protein are remarkably mutated. A few deleterious mutations in the above domains are also observed. The NSPs of SARS-CoV-2, the highly conserved components in the life cycle of CoVs, are named as NSP1 to NSP16 and they act as enzymes, coenzymes, and binding proteins to facilitate the replication, transcription, and translation of the virus. The 16 NSPs are the leader protein (NSP1), the NSP2, the papain-like protease (PLpro, NPS3), the NSP4, the 3C-like protease (or called main protease, 3CLpro, Mpro, NSP5), the NSP6, the NSP7, the NSP8, the replicase protein (NSP9), the NSP10, the NSP11, the RNA-directed RNA polymerase (RdRp, NSP12) – RdRp variant P323L, the RNA-helicase (NSP13), the guanine-N7 methyltransferase protein (MTase, NSP14), the uridylate-specific endonuclease/endoribonuclease protein (NSP15), the 2’-O-methyltransferase (NSP16), and their complexes. The APs of SARS-CoV-2 participate in the viral replication, assembly, and virus-host interactions. The SARS-CoV-2 accessory proteins are ORF1a, ORF1ab, ORF3a, ORF4a, ORF6, ORF7a, ORF7b, ORF8, ORF9b, ORF9c, and ORF10. Mutations in ORF1ab, ORF3, ORF6, and ORF8 are observed during the COVID-19. Because APs have too much variation between viruses, APs are not good drug targets. Hence, two types of anti-coronavirus drug targets are: S-, E-, M-, and Nproteins of SPs (especially the S-protein) and NSP1-NSP16 of NSPs (especially the 3CLpro (NSP5), RdRp (NSP12), PLpro (NSP3), and helicase protein (NSP13)). Therefore, the search for drug development targets and repositioning of existing therapeutics is essential for fighting the present COVID-19 pandemic. This book studies the following proteins and their drug bindings: PLpro, 3CLpro, RdRp, RNA-helicase, RNA-helicase binding with NSP12-ADTPMg2, RNA-helicase binding with ADTPMg2, spike, D614G mutant, N501Y mutant, N165A-and-N234A mutant, SARS, MERS, human-ACE2, human-L6, humanL6R, PLpro-monomer binding with 12 drugs, 3CLpro-monomer binding with drugs, 3CLpro-dimer binding with drugs, S-protein binding with 50 drugs, humanACE2 binding with 78 drugs, S-protein and human-ACE2 binding with 100 drugs, E-protein, M-protein, N-protein, RNA genome, NSP7, NSP8, NSP9, NSP10, NSP10-NSP16 complex, NSP16, NSP10-NSP14 complex, NSP14, NSP15, and other-mutants (including alpha-, alpha1-, alpha2-, beta-, delta-, epsilon-, gamma-, kappa-, omicron-variants). Vaccines (such as Pfizer, Moderna, AstraZeneca, Janssen, Sinopharm, Covaxin, Novavax, Icosavax), drugs, antigen rapid test (ART), pandemic mathematical models (including time-delays models), epidemiology and virus origins etc. are also introduced in this book. This book first did local optimization (because of the three-body movement) of each molecular structure. The optimized structure is at a transition state with the best stability and the lowest energy. The hybrid strategy of mathematical optimization’s neighboring different (local search) algorithms is used. The optimization strategy will significantly reduce the scale of data and at the same time get rid of useless bioinformatics. To really understand the stability of molecules and their action mechanism, we should consider not only the static NMR, X-ray, or cryo-EM structures concerned but also the dynamical information obtained by Molecular Dynamics (MD) or Quantum Mechanics/Molecular Mechanics (QM/MM) simu-
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lating their internal motions or dynamic process. Secondly, for each protein, we will confirm the structural bioinformatics gotten from the optimized structure by analyzing the large-scale MD trajectory databases, where all the MD trajectory databases are the ones that can be openly and freely available on-line. The strong network of hydrogen bonds and hydrophobic interactions along with van der Waals interactions inhibit receptors, which are essential to the entry and replication of the SARS-CoV-2. Basic structural bioinformatics such as hydrogen bonds, salt bridges, .π -interactions, secondary structures, RMSD and RMSF etc. of each SARS-CoV-2 protein are presented in this book. Biological mathematics models are also studied in this book. To understand this book needs some basic knowledge on biochemistry, biophysics, biomedicine, mathematical optimization and statistical analysis, etc.; we list the basic knowledge as the Appendix. The intended audiences of this book are researchers in computational biochemistry, computational biophysics, optimization and molecular dynamics, structural bioinformatics, biological mathematics, statistical analysis, etc. Clearly, structurebased drug designing or discovery research staff will be also benefited from some original results of this book. For students or teachers, they might also quickly know all the molecular structures and their structural dynamics of SARS-CoV-2. As an accessible introduction to these fields, this book is also ideal as a teaching material for students. Acknowledgments This research (with project no. pb04 at Federation University Australia and under NCI) was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government. I wish to thank all those who have helped me in one way or another. This book systematically united my research results during COVID19 pandemic years but without any research fund support; thus, I am deeply in debt to my wife Grace Xiao-Yan Yuan for her patience and accompany during this research. Last but not least, Springer Nature’s team are gratefully acknowledged; Professors Dzalilov Z, Bagirov AM et al. are also gratefully acknowledged for their kind help, support and encouragement. Ballarat, VIC, Australia April, 2023
Jiapu Zhang
Contents
1
Papain-Like Cysteine Protease (PLpro). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Structural Bioinformatics Results and Discussions . . . . . . . . . . . . . . . 1.3.1 Monomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.2 Dimer Without Inhibitor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.3 The C111S Mutant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.4 Compared with SARS-CoV-1-PLpro . . . . . . . . . . . . . . . . . . . . 1.3.5 Inhibitors S43, GRL0617, XR8-89, JUN9-84-3, and JUN9-72-2 Bindings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1 1 2 3 3 6 8 9 10 11
2
3C-Like Protease (3CLpro) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.1 Monomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.2 Dimer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.1 Monomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.2 Dimer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3.3 Comparison with SARS-CoV-1-Mpro . . . . . . . . . . . . . . . . . . . 2.3.4 Comparison with SARS-CoV-1-Mpro-N3 . . . . . . . . . . . . . . . 2.3.5 Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
33 33 34 34 34 35 35 39 55 56 59 61
3
RNA-Dependent RNA Polymerase (RdRp) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 New Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
161 161 162 163 170
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RNA Helicase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 New Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
195 195 196 196 203
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RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA, .ADP-Mg2+ , and .ATP-Mg2+ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 New Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
227 227 228 228 231
RNA Helicase Binding with ADP-Mg2+ , ATP-Mg2+ , and RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.3 New Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
243 243 244 244 246
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Spike (S) Glycoprotein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.1 Trimeric SARS-CoV-2 S . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.2 Human ACE2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.3 Binding of SARS-CoV-2 S-RBD and Human ACE2 . . . . 7.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3.1 The 6VXX (SARS-CoV-2 S Close) Model: Model1 . . . . 7.3.2 The 6VYB (SARS-CoV-2 S with One SB Open) Model: Model2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3.3 The 1R4L (ACE2 Close) Model: Model3. . . . . . . . . . . . . . . . 7.3.4 The 1R42 (ACE2 Open) Model: Model4 . . . . . . . . . . . . . . . . 7.3.5 The 6M17 (B0 AT1) Model: Model5 . . . . . . . . . . . . . . . . . . . . . 7.3.6 The 6VW1 (Chimera) Model: Model6 . . . . . . . . . . . . . . . . . . . 7.3.7 Glycans’ Shields . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3.8 Spike-Trimer Binding with Nanobody-Nb6c . . . . . . . . . . . . 7.3.9 The RGD Motif of Spike-RBD . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
263 264 264 264 265 265 267 267
Spike (S) Glycoprotein D614G Mutant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2 Homology Structures of D614G Mutant . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.3 Structural Bioinformatics of D614G Mutant . . . . . . . . . . . . . . . . . . . . . . 8.3.1 6vxx-Close-D614G-Mutant. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.3.2 6vyb-Open-D614G-Mutant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.1 Confirmed from Some MD Datasets . . . . . . . . . . . . . . . . . . . . .
327 327 327 328 328 329 331 332
268 270 271 273 275 281 282 283 283
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Spike (S) Glycoprotein N501Y Mutant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2 The Homology Structure of N501Y Mutant . . . . . . . . . . . . . . . . . . . . . . . 9.3 Structural Bioinformatics of N501Y Mutant . . . . . . . . . . . . . . . . . . . . . . 9.3.1 From the optimized-6m17-N501Y-mutant Model . . . . . . . 9.3.2 From MD Simulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
349 349 350 350 350 354 355
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Spike (S) Glycoprotein N165A and N234A Mutant . . . . . . . . . . . . . . . . . . . . . 10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.3 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
359 360 360 360 364
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SARS (SARS-CoV-1) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3 New Structural Bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3.1 SARS-CoV-1 Spike in Folding@home . . . . . . . . . . . . . . . . . . 11.3.2 HCoV-NL63 Spike in Folding@home . . . . . . . . . . . . . . . . . . . 11.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
393 393 394 394 397 399 401
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MERS-Coronavirus (MERS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.3 New Structural Bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
417 417 418 418 419
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Human ACE2, Human IL6, Human IL6R, and Human nAChRs . . . . 13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3 New Structural Bioinformatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3.1 Human ACE2 Monomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3.2 Human IL6 Monomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3.3 Human IL6R Monomer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3.4 Human α4β2-, α7-, and αβγ δ-nAChR . . . . . . . . . . . . . . . . . . 13.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
423 423 424 424 424 427 431 432 438
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PLpro Binding with 12 Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
445 445 445 446 448
15
3CLpro Binding with N3/Lopinavir/Ritonavir . . . . . . . . . . . . . . . . . . . . . . . . . . 15.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.2.1 N3 at the Binding Pocket of SARS-CoV-2 Mpro . . . . . . . .
457 457 458 458
xiv
Contents
15.2.2
15.3
15.4
Lopinavir at the Binding Pocket of SARS-CoV-2 Mpro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.2.3 Ritonavir at the Binding Pocket of SARS-CoV-2 Mpro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.2.4 Top 100 Drugs Binding with SARS-CoV-2 Mpro . . . . . . . 15.2.5 X77 Inhibitor Binding with SARS-CoV-2 Mpro . . . . . . . . Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.3.1 N3 at the Binding Pocket of SARS-CoV-2 Mpro . . . . . . . . 15.3.2 Lopinavir at the Binding Pocket of SARS-CoV-2 Mpro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.3.3 Ritonavir at the Binding Pocket of SARS-CoV-2 Mpro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15.3.4 Top 100 Drugs Binding with SARS-CoV-2 Mpro . . . . . . . 15.3.5 X77 Inhibitor Binding with SARS-CoV-2 Mpro . . . . . . . . Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
458 459 459 459 460 460 461 463 466 467 469
16
3CLpro Dimer Binding with 7 HIV Inhibitors and Others . . . . . . . . . . . . 16.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.2.1 7 HIV Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.2.2 2A5I-Ligand, 2OP9-Ligand, and 6LU7-Indinavir . . . . . . . 16.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.3.1 7 HIV Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16.3.2 2A5I-Ligand, 2OP9-Ligand, and 6LU7-Indinavir . . . . . . . 16.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
479 479 479 479 480 480 480 482 488
17
Spike RBDs Binding with 50 Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
511 511 512 512 513
18
Human ACE2 Ectodomain Binding with 78 Drugs . . . . . . . . . . . . . . . . . . . . . 18.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
529 529 530 530 531
19
Spike-and-ACE2 Binding with 100 Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
545 545 546 546 547
20
Envelope Protein (E-Protein) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557 20.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 557 20.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
Contents
20.3
Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20.3.1 7K3G.pdb . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20.3.2 7M4R.pdb . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20.3.3 MD of “Single E-protein Pentamer in Membrane” . . . . . . 20.3.4 The Optimized “Four E-protein Pentamers in Membrane” Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
560 560 560 561
Membrane Glycoprotein (M-Protein) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21.3.1 MD on the “Single M-Protein Dimer in Membrane” . . . . 21.3.2 The Optimized “Three M-Protein Dimers and One E-Protein Pentamer in Membrane” Model. . . . . . . . . . 21.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
573 573 574 574 576
Nucleocapsid Phosphoprotein (N-Protein) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22.3.1 The N-Protein’s C-Terminal Tail PRO365-ALA419 Monomer Model . . . . . . . . . . . . . . . . . . . . . 22.3.2 The N-Protein’s C-Terminal Tail PRO365-ALA419 Dimer Model . . . . . . . . . . . . . . . . . . . . . . . . . 22.3.3 The N-Protein’s Full-Length MET1-ALA419 Dimer Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22.3.4 The N-Protein’s Full-Length MET1-ALA419 Dimer with RNA G1-C60 Model . . . . . . . . . . . . . . . . . . . . . . . . 22.3.5 The N-Protein’s Full-Length MET1-ALA419 Octamer with the Four RNAs Model. . . . . . . . . . . . . . . . . . . . . 22.3.6 The N-Protein’s Dimerization-Domain THR247-PRO364 Dimer Model . . . . . . . . . . . . . . . . . . . . . . . . . 22.3.7 The N-Protein’s RBD ALA50-ALA173 Monomer Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
597 597 600 601
20.4 21
22
xv
566 567
585 596
601 603 614 616 620 621 627 629
23
SARS-CoV-2 RNA Genome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 639
24
NSP7, NSP8, NSP9, NSP10, NSP16, and NSP14 . . . . . . . . . . . . . . . . . . . . . . . . 24.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.3.1 NSP7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.3.2 NSP8 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.3.3 NSP9 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.3.4 NSP10 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
645 645 655 655 655 656 658 660
xvi
Contents
24.3.5 NSP10-NSP16 Complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.3.6 NSP16 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.3.7 NSP10-NSP14 Complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24.3.8 NSP14 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
663 665 667 670 675
25
NSP15 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
711 711 714 714 716
26
Other Mutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26.2 Materials and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26.3 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26.3.1 The Alpha-, Beta-, Delta-, and Kappa-variant of [288] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26.3.2 The P.1-Variant (i.e., Gamma-Variant) of [58, 253] . . . . . 26.3.3 The Alpha1-, Alpha2-, Beta-, and Delta-variant and the wt of [68] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26.3.4 The Alpha-, Beta-, Delta-, Epsilon-, Kappa-, and Omicron-variant of [284] Optimized . . . . . . . . . . . . . . . . 26.3.5 Omicron-Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26.4 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
723 723 723 724
27
Vaccines and Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.2 Pfizer-BioNTech COVID-19 Vaccine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.2.1 Bivalent Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.3 Moderna COVID-19 Vaccine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.4 Oxford-AstraZeneca COVID-19 Vaccine. . . . . . . . . . . . . . . . . . . . . . . . . . 27.5 Janssen COVID-19 Vaccine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.6 Sinopharm BIBP COVID-19 Vaccine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.7 Covaxin COVID-19 Vaccine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.8 Novavax COVID-19 Vaccine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.9 Antigen Rapid Test (ART). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.10 Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27.11 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
887 887 888 890 890 892 893 893 894 894 894 895 896
28
Pandemic Mathematical Models, Epidemiology, and Virus Origins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28.2 Pandemic Mathematical Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28.3 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28.4 Origins of SARS-CoV-2 Virus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28.5 Concluding Remarks. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
897 897 897 905 907 908
24.4
724 729 735 766 771 872
Contents
A
xvii
Mathematical Optimization Algorithms and Free Energy Calculations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 909
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 915 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 945
Acronyms
3CLpro 3D aa ACE2 APs BFGS CG chon2 chon4 CoVs CS1 CTD dex2 dex4 DSSP E-protein EPS FMNR GA GO GROMACS h6s2 h6s4 HB hep2 hep4 HYD L-BFGS
3C-like protease three-dimensional amino acid angiotensin converting enzyme 2 accessory proteins Broyden-Fletcher-Goldfarb-Shanno quasi-Newton algorithm conjugate gradient method chondroitin sulfate dimer chondroitin sulfate tetramer Coronaviruses cleavage site S1 C-terminal domain dextran sulfate dimer dextran sulfate tetramer Database/Dictionary of Secondary Structures of a Protein envelope protein electrostatic potential surfaces full matrix Newton Raphson genetic algorithm global optimization Groningen machine for chemical simulations heparan sulfate dimer heparan sulfate tetramer hydrogen bond heparin dimer heparin tetramer hydrophobic interaction limited-memory Broyden-Fletcher-Goldfarb-Shanno quasi-Newton algorithm
xix
xx
lbfgs-TNCG LMOD MC MD MERS Mpro Mpro-dm M-protein MSIR MTase nAChRs NMR N-protein NSPs NTD ORFs OSVM PD PDB PLpro PRCG RBD RdRp RMS RMSD RMSF RTC SA SARS SASA SB SD SEIR SI SIMPLEX SIMPLEX-GENETIC SIR SIRD SIRS SIS S-protein SPs TNCG vdW wt
Acronyms
L-BFGS preconditioned truncated Newton conjugate gradient algorithm low-MOD methods Monte Carlo molecular dynamics Middle East respiratory syndrome main protease Mpro-delP168-and-a173v membrane glycoprotein immunity-susceptible-infected-recovered methyltransferase protein nicotinic acetylcholine receptors nuclear magnetic resonance nucleocapsid phosphoprotein non-structural proteins N-terminal domain open reading frames Oren-Spedicato Variable Metric peptidase domain Protein Data Bank papain-like protease Polak-Ribiere conjugate gradient method receptor-binding domain RNA-directed RNA polymerase root mean square root mean square deviation root mean square fluctuation replication-transcription complex simulated annealing severe acute respiratory syndrome solvent accessible surface area salt bridge steepest descent algorithm susceptible-latent-infected-recovered susceptible-infected the downhill simplex minimizer the hybrid simplex-genetic algorithm susceptible-infected-recovered susceptible-infected-recovered-deceased susceptible-infected-recovered-susceptible susceptible-infected-susceptible spike glycoprotein structural proteins truncated Newton conjugate gradient van der Waals wild-type
Chapter 1
Papain-Like Cysteine Protease (PLpro)
Abstract Viral papain-like cysteine protease (PLpro, NSP3) is essential for SARSCoV-2 replication and represents a promising drug target against SARS-CoV-2 virus. Fortunately, the crystal structure of SARS-CoV-2-PLpro in complex with peptide inhibitor VIR251 was already released into Protein Data Bank (PDB) on May 20, 2020 with PDB entry 6WX4. This chapter is firstly optimizing this structure of the monomer and dimer, with and without the inhibitor. Then, basing from the optimized models, we present some structural bioinformatics for SARS-CoV2-PLpro monomer (with/without the inhibitor) and dimer (without the inhibitor). The structural bioinformatics of this brief chapter might be useful or helpful for developing therapies against the currently fatal SARS-CoV-2 virus. For PLpro, we found some preliminary interesting results such as (1) the polar contacts ASP76ARG82 and ASP286-HIS272 are very important for keeping the monomer structure stable, (2) the broken of salt bridge GLU307-LYS217 might lead to some motion in the C-terminal residues, and (3) for the dimer the polar contacts GLU143ARG138 and hydrogen bonds ARG140.H-TYR137.OH make the two monomers (of a dimer) linking to each other, etc. For the SARS-CoV-2-PLpro C111S mutant, the SB GLU67-HIS17 cannot be maintained during MD simulation because of ion ZN503. Comparisons with SARS-VoV-1-PLpro and the binding sites for inhibitors S43, GRL0617, XR8-89, JUN9-84-3, JUN9-72-2 are also studied in this chapter. Keywords SARS-CoV-2-PLpro · Monomer and dimer and trimer · With/without inhibitor · Structural bioinformatics · Optimization and molecular dynamics
1.1 Introduction Paper [297] provides the structure of inhibitor-bound SARS-CoV-2-PLpro (with PDB entry 6WX4) and recently molecular dynamics (MD) 100-.μs trajectory data for 6WX4 removing the covalent inhibitor was released on July 15, 2020 [321]. Thus, we have data resources to study the static and dynamic structural behaviours of SARS-CoV-2-PLpro. We organize this chapter as two parts: the first part will © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_1
1
2
1 Papain-Like Cysteine Protease (PLpro)
discuss SARS-CoV-2-PLpro monomer without and with the inhibitor, and the second part is discussing SARS-CoV-2-PLpro dimer models without the inhibitor.
1.2 Materials and Methods The material used in the chapter is 6WX4.pdb. 6WX4.pdb has two chains: D-Chain is the structure of PLpro, and I-Chain is the structure of the inhibitor VIR251. Basing on 6WX4.pdb (i.e. the monomer with the inhibitor), we built four models: (model1) a monomer without the inhibitor (i.e. D-Chain only) and (model2 to model4) three dimers without the inhibitor I-Chain. The methods of this chapter are the optimization computations and MD trajectory data analyses (in this book packages such as VMD [154], SWISS-MODEL and Swiss-PdbViewer [133, 134], Maestro-10.1, Amber, etc. are used to analyse the MD trajectories). We first optimize the above four models (why the models need to optimize can be seen from Page 8 of [411]). Optimized structure in a transition state is much more stable. The hybrid strategy of mathematical optimization’s neighbouring different local search algorithms [405] is used for the optimization computing. For the MD trajectory data analyses, because the noncovalent interactions of hydrogen bonds (HBs), salt bridges (SBs), van der Wales contacts (vdWs), and hydrophobic interactions (HYDs) are driving a protein to be able to perform its biological functions (Page 167 of [411]), in the below we will find out the HBs, SBs, HYDs, and vdWs of the four models and the optimized 6WX4.pdb. The performances of the MD trajectory data are evaluated by the MD analysis methods of [412] (Pages 8–10). In addition, the PLpro C111S mutant is also studied in this chapter. In [332], the supervised MD-trajectories datasets for PLpro in complex with the inhibitors GRL0617, SNYDER495, SNYDER530, and SNYDER441 are presented for the PDB entries 7cmd, 7jit, 7jiw, and 7jn2, respectively. In this chapter, we choose the two files in directory /Data/7JIT-S495/7JIT-Unbinding-rep1/ of [332]: Concat-Unbinding-SuMD-7JIT-rep1-fit-fit-2260.gro and Concat-UnbindingSuMD-7JIT-rep1-fit-fit.xtc. In http://chemcha-gpu0.ucr.edu/software/, there are five sets of PLpro 1.μs MD trajectories for (1) SARS-CoV-2-PLpro-wt (C-chain of 6W9C.pdb: aa THR4-ILE314 without ligand), (2) SARS-CoV-2-PLpro-C111S-mutant (A-chain of 6WRH.pdb: aa THR4-ILE314 without ligand), (3) SARS-CoV-2-PLpro-wt ligand-bound (A-chain of 6W9C.pdb: aa THR4-LYS315 with ligand S88), (4) SARS-CoV-1-PLpro-wt (A-chain of 4OW0.pdb: aa LYS4-THR5-..-ILE315 without ligand), and (5) SARS-CoV-1-PLpro-wt ligand-bound (A-chain of 4OW0.pdb: aa THR5-ILE315 with ligand S88), respectively, where the residue numbers of SARSCoV-2 should be added 1 to agree with the ones of SARS-CoV-1. In this chapter, we also study the optimized structures of these five models and present their MD results.
1.3 Structural Bioinformatics Results and Discussions
3
1.3 Structural Bioinformatics Results and Discussions 1.3.1 Monomer 1.3.1.1
Without Inhibitor
The optimized monomer without the inhibitor (with 0.146302 Å of backbone RMSD from the unoptimized structure) has 4 SBs ASP76-ARG82, ASP286-HIS272, ASP62-ARG65, GLU67-HIS17; 145 HBs; 1 .π-cation LYS.+ 92.NZ-HIS89, 3 .π.π stackings TYR71-TYR72, TYR136-TYR137, and TYR264-TYR273; and lower Solvent Accessible/accessibility Surface Area (SASA) values at PRO129-PRO130ALA131 and SER245-ALA246-PRO247 and larger SASA values at TYR136TYR137-ARG138 and PHE216-LYS217-LYS218. From the 100-.μs MD trajectory data with 100,000 frames of [321], we picked up 1000 frames with a frame interval of 100 ns. From analyses of the 1000 frames, we get 59 SBs and 1112 HBs. Seeing Fig. 1.1, we can confirm the stronger SBs ASP76-ARG82 (ARG82.NH2-ASP76.OD2 (11.29%), ARG82.NH2-ASP76.OD1 (11.19%), ARG82.NH1-ASP76.OD2 (2.40%), and ARG82.NH1-ASP76.OD1 (1.70%)—wherein the brackets are the HB occupancy rates), ASP286-HIS272 (HIS272.NE2-ASP286.OD1 (23.78%), HIS272.NE2-ASP286.OD2 (20.48%)), and the very weaker SBs ASP62-ARG65 and GLU67-HIS17. Thus, we may say the polar contacts ASP76-ARG82 and ASP286-HIS272 are very important for keeping the structure stable.
Other 17 SBs such as GLU263-LYS274 (with HBs GLU263.N-LYS274.O (40.46%), LYS274.NZ-GLU263.OE2 (20.08%), LYS274.N-GLU263.O (19.08%),
Fig. 1.1 The 4 SBs (of the optimized model) ASP76-ARG82, ASP286-HIS272, ASP62-ARG65, and GLU67-HIS17 confirmed by MD trajectory data of [321]
4
1 Papain-Like Cysteine Protease (PLpro)
LYS274.NZ-GLU263.OE1 (18.58%)), GLU167-LYS157, GLU214-LYS217, GLU252-LYS254, GLU295-LYS254, GLU307-LYS217 (first 20 .μs), GLU1ARG3, GLU143-ARG138 (with HBs ARG138.NH2-GLU143.OE1 (10.19%), ARG138.NH2-GLU143.OE2 (9.69%), ARG138.NE-GLU143.OE1 (4.90%), ARG138.NE-GLU143.OE2 (3.90%)), GLU161-LYS157, ASP302-ARG166 (with HB ARG166.NE-ASP302.OD1 (11.29%)), GLU124-ARG140, GLU124-LYS126, GLU214-LYS218 (with HB LYS218.N-GLU214.O (23.18%)), GLU238-LYS182 (with HBs GLU238.N-LYS182.O (28.37%), LYS182.N-GLU238.O (26.77%)), GLU252-LYS297, GLU318-HIS320, and GLU318-LYS315 can be seen from Fig. 1.9. From Fig. 1.9, we may see that the polar contacts GLU263-LYS274, GLU143-ARG138, ASP302-ARG166, GLU214-LYS218, and GLU238-LYS182 are also contributing to the structural stability. We list the HBs with more than 30% occupancy rates during the 100 .μs in Table 1.1. We know residues TYR72, TYR136, and TYR264 are key residues: (i) at residue TYR72 there are one .π-.π stacking TYR72-TYR71 and three strong HBs TYR72.OH-VAL11.O (49.45%), TYR72.N-ALA68.O (35.86%), and TYR72.O-TYR154.OH (55.84%), (ii) at residue TYR136 there is one .π-.π stacking TYR136-TYR137, one HB TYR136.O-ARG140.N (46.55%), and a hydrophilic region TYR136-TYR137-ARG138, and (iii) at residue TYR264 there is one .π -.π stacking TYR264-TYR273 and two strong HBs TYR264.N-ASN267.O (30.37%) and TYR264.N-PRO299.O (36.56%). From Table 1.1, we know the HBs in segments VAL165-MET169-PHE173, LYS94-LYS105-ASN110, PHE79-TYR83LEU87, LEU113-LEU117-GLN121, ASN146-LEU150-TYR154, TYR83-LEU87LYS91, and ALA86-THR90-TYR95 contribute to maintain the structural stability locally. The 100 .μs’ MD RMSD, Secondary Structures, and RMSF performances are illuminated in Fig. 1.2.
From Fig. 1.2, as said in [321], “the overall structure is fairly stable, some motion in the microsecond timescale is observed in the loops and in the (C)terminal residues.” The RMSD values reach equilibrations around 2.1 Å during the first 22 .μs and then around 4.8 Å during 23–100 .μs—during 22–23 .μs there is a jump (for example) because of the broken of SB GLU307-LYS217 (Fig. 1.9) (but HBs GLU307.N-PRO240.O (21.48%), THR311-GLU307 (N-O 14.69%, OG1O 10.09%), and TYR310.N-GLU307.O (5.79%) (Table 1.1 and Fig. 1.10) are
1.3 Structural Bioinformatics Results and Discussions
5
Fig. 1.2 The 100 .μs’ MD RMSD, Secondary Structures, RMSF performances, and SB GLU307LYS217
complementary to the SB GLU307-LYS217)—thus leading to the structure around segment GLU307-SER309 changed from Coil into 3.10 -helix.
1.3.1.2
With the Inhibitor
The optimized monomer with the inhibitor is with 1.093729 Å of backbone RMSD from the unoptimized structure. 6WX4.pdb has 3 .π -cations LYS.+ 92.NZHIS89, LYS274.+ .NZ-HIS272, LYS217.+ .NZ-TYR310 and 4 .π -.π stackings TYR71-TYR72, TYR136-TYR137, TYR264-TYR273, and HIS50-PHE55; after optimization, the .π -interactions LYS274.+ .NZ-HIS272, LYS217.+ .NZ-TYR310, and HIS50-PHE55 were lost. For the 6WX4optimized structure, its Ligand Interaction Diagram can be seen in Fig. 1.3, where there are HBs I:GLY4.HD:GLY163.O (1.85 Å), I:GLY4.O-D:GLY163.H (1.94 Å), I:DPP3.O-D:GLY271.H (2.08 Å), and I:DPP3.O-D:TYR264.H (2.60 Å). For the 6WX4optimized structure, the distances around Zn.2+ are illuminated in Fig. 1.4.
6
1 Papain-Like Cysteine Protease (PLpro)
Fig. 1.3 The Ligand Interaction Diagram and 4 HBs around the inhibitor
Fig. 1.4 The atom distances from the ion Zn.2+ with 2 HBs CYS189.O-CYS192.H (2.03 Å) and CYS224.O-CYS226.H (2.72 Å)
1.3.2 Dimer Without Inhibitor We applied the following mathematical formulas: ⎞ −1 0 0 .C = ⎝ 0 −1 0 ⎠ D, 0 0 1 ⎛
⎞ −1 0 0 C = ⎝ 0 1 0 ⎠ D, 0 0 −1 ⎛
⎞ 1 0 0 C = ⎝ 0 −1 0 ⎠ D 0 0 −1 ⎛
(1.1)
to 6WX4.pdb building three dimers and then optimized the three models of dimer without inhibitor (with backbone RMSD values of 2.171411 Å, 1.848472 Å, and 1.853466 Å, respectively, from the unoptimized ones). We denote the models as dimer-1, dimer-2, and dimer-3. For dimer-1, we get 10 SBs D:GLU143-C:ARG138, C:GLU143-D:ARG138, D:ASP286-D:HIS272, C:ASP286-C:HIS272, C:ASP62-C:ARG65, D:ASP62D:ARG65, D:GLU67-D:HIS17, C:GLU67-C:HIS17, C:ASP76-C:ARG82, and D:ASP76-D:ARG82 and 63 HBs. There are two HBs GLU143.OE2-ARG138.H (2.35 Å) between the two monomers (Fig. 1.5). Thus, the polar contacts GLU143ARG138 make the two monomers linking to each other. Seeing Fig. 1.5, we know the HBs ARG140.H-TYR137.OH (2.40 Å) also make the two monomers linking to each other.
1.3 Structural Bioinformatics Results and Discussions
7
Fig. 1.5 The polar contacts GLU143-ARG138 and the HBs ARG140.H-TYR137.OH (2.40 Å) are between the two monomers of dimer-1
For dimer-2, we found the Poisson–Boltzmann Electrostatic Potential Surfaces and the Hydrophilic Surfaces of the two monomers are touching to each other (Fig. 1.6).
Fig. 1.6 The Poisson–Boltzmann Electrostatic Potential Surfaces and the Hydrophobic/Hydrophilic Surfaces of dimer-2
In dimer-2, there are 2 extra .π -cations LYS.+ 274.NZ-HIS272 and LYS.+ 217.NZTYR310 in each monomer and 1 extra .π -.π stacking PHE55-HIS50 in each monomer. For dimer-3, the results are similar to those of dimer-2 (Fig. 1.7), and there are 2 extra .π -cations LYS.+ 274.NZ-HIS272 and LYS.+ 217.NZ-TYR310 in each monomer and 1 extra .π -.π stacking PHE55-HIS50 in each monomer.
Fig. 1.7 The Poisson–Boltzmann Electrostatic Potential Surfaces, the Hydrophobic/Hydrophilic Surfaces, and the vdW Surfaces (with vdW radius scale 1.0) of dimer-3
8
1 Papain-Like Cysteine Protease (PLpro)
1.3.3 The C111S Mutant In [332], the Concat-Unbinding-SuMD-7JIT-rep1-fit-fit.xtc has 1604 MD-frames, where 7JIT.pdb is the crystal structure of SARS-CoV-2-PLpro C111S mutant in complex with the SNYDER495 inhibitor. The residues in 7JIT.pdb are aa VAL2LYS315, Y95-501, ZN502-503-504-505, CL506-507-508, MES509, and ACT510511. The MD RMSD values are stable, but the RMSF values in segment aa 182–202 around residue 192 are larger, and at residue 92 its RMSF value is also larger. The MD Secondary Structure performance can be seen from Fig. 1.8, where the .α-helix aa THR26-GLY32 has slight changes into Turns or .310 -helix.
Fig. 1.8 The MD Secondary Structure of the SARS-CoV-2-PLpro C111S mutant during 1604 MD-frames
Table 1.2 lists the HBs (with more than 5% occupancy rates) of the SARSCoV-2-PLpro C111S mutant from the analyses of the 1604 frames’ supervised MD trajectory data (Concat-Unbinding-SuMD-7JIT-rep1-fit-fit.xtc) of [332]. The MD finds 662 HBs and 31 SBs as follows: ASP37-LYS91, ASP40-LYS43, GLU51-LYS6, ASP62-ARG65, GLU70-HIS73, ASP76-ARG82, ASP108-HIS89, ASP108-LYS92, GLU124ARG140, GLU124-LYS126, GLU124-LYS306, ASP134-ARG138, GLU143-ARG138, GLU161LYS157, ASP164-ARG166, GLU167-ARG166, GLU167-LYS157, ASP179-LYS200, GLU214LYS217, GLU214-LYS218, GLU238-LYS182, GLU252-LYS254, GLU252-LYS297, GLU263LYS274, GLU280-LYS279, GLU280-LYS292, ASP286-HIS272, ASP286-LYS274, GLU295LYS254, ASP302-ARG166, and GLU307-LYS217.
We optimize 7JIT.pdb (without HOH waters) and get three .π -.π stackings TYR71-TYR72, PHE127-TYR136, and TYR273-TYR264 and two .π -cations LYS217.NZ.+ -TYR310 and LYS279.NZ.+ -TYR283; the ions bindings ZN502CYS189/192/224/226.SG, CL506-HID17.NE2-ZN503-GLU67.OE2, HID89.ND1-
1.3 Structural Bioinformatics Results and Discussions
9
ZN504-ASP108, HID73.ND1-ZN505-CL507/8, the ACT510 binding with PLpro residues SER111, TRP106, ASN109 ASN110, HIS272, GLY271, and the ligand Y95.501 binding with PLpro residues GLU167, ASP164, LEU162, GLN269, THR301, TYR264, TYR273, PRO248, MET208, TYR268, and ACT511. The Poisson–Boltzmann Electrostatic Potential Surfaces seem to be neutral for almost all surfaces. The optimized structure has 16 SBs ASP37-LYS91, GLU51-LYS6, GLU67-HIS17, GLU238-LYS182, GLU252-LYS297, GLU295-LYS254, GLU307LYS217, ASP62-ARG65, ASP76-ARG82, GLU143-ARG138, GLU161-LYS157, GLU167-LYS157, GLU214-LYS218, GLU252-LYS254, GLU280-LYS292, and ASP286-LYS274, where the SB GLU67-HIS17 is not appearing during the supervised MD (but with HBs HIS17.N-THR9.O 31.92% and THR9.OG1-HIS17.O 14.40%) (Figs. 1.9 and 1.10).
1.3.4 Compared with SARS-CoV-1-PLpro In this subsection, we study the five models: (1) SARS-CoV-2-PLpro-wt (C-chain of 6W9C.pdb: aa THR4-ILE314 without ligand), (2) SARS-CoV-2-PLpro-C111Smutant (A-chain of 6WRH.pdb: aa THR4-ILE314 without ligand), (3) SARSCoV-2-PLpro-wt ligand-bound (A-chain of 6W9C.pdb: aa THR4-LYS315 with ligand S88), (4) SARS-CoV-1-PLpro-wt (A-chain of 4OW0.pdb: aa LYS4-THR5..-ILE315 without ligand), and (5) SARS-CoV-1-PLpro-wt ligand-bound (A-chain of 4OW0.pdb: aa THR5-ILE315 with ligand S88) presented in http://chemchagpu0.ucr.edu/software/. The residue numbers of SARS-CoV-2 in 6W9C.pdb and 6WRH.pdb should be added 1 to agree with the ones of SARS-CoV-1 in 4OW0.pdb. For the ligand S88, the following residues LEU162, GLY163, ASP164, ARG166, MET208, PRO247, PRO248, TYR264, ASN267, TYR268, GLN269, TYR273, and THR301 are the common residues binding with S88 not only in SARS-CoV-2PLpro (model 3) but also in SARS-CoV-1-PLpro (model 5); two additional residues LYS158 and GLY267 are also involved to binding the ligand S88 in SARS-CoV-1PLpro (model 5). Table 1.3 lists all the SBs of the five PLpro models optimized, where we can see that all the five models have common SBs GLU238-LYS182, ASP286HIS272 (but during MDs it is replaced by ASP286-LYS274), GLU161-LYS157, and GLU214-LYS217; but the mutation made SBs ASP40-LYS43, ASP164ARG166 lost in the four wt models. During 1 .μs’ MDs, the following SBs are kept for all the five models: ASP37-LYS53, ASP37-LYS91, GLU51-LYS6, ASP76-ARG82, ASP108-LYS92, GLU124-ARG140, GLU124-LYS279, GLU143-ARG138, GLU161-LYS157, GLU167-LYS157, ASP286-LYS274, GLU307-LYS217, ASP40-LYS43, ASP134-ARG138, ASP164-ARG166, GLU280-LYS279,
GLU124-LYS306, GLU143-LYS91, GLU214-LYS217, GLU238-LYS182, ASP62-ARG65, GLU124-LYS126, and GLU295-LYS297 (Table 1.4).
We also can confirm the SBs ASP76-ARG82, ASP286-LYS274, GLU307-LYS217, and GLU143-ARG138 are maintained during 1 .μs’ MDs. Tables 1.5 and 1.6 list all the HBs of the five PLpro models optimized. Tables 1.7, 1.8, and 1.9 list all the HBs (with more than 30% occupancy rates)
10
1 Papain-Like Cysteine Protease (PLpro)
of the five PLpro models maintained during 1 .μs’ MDs. Table 1.10 lists all the π -interactions and ZN316 binding residues of the five PLpro models in chemchagpu0.ucr.edu/software/ optimized, where CYM189 is always binding with ZN316. Figure 1.11 illuminates the Secondary Structures performances of the five PLpro models during 1 .μs’ MDs, where we know for models SARS-CoV-2 wt and SARS-CoV-1 wt with/without ligand S88 the two segments GLY28-THR34 around VAL202 have larger variations; but for the SARS-CoV-2 C111S-mutant, its larger variations are in segments GLY39-THR35 and around VAL203. We also know there are slight differences among the five models from the Secondary Structures of the five models optimized (Fig. 1.11).
.
1.3.5 Inhibitors S43, GRL0617, XR8-89, JUN9-84-3, and JUN9-72-2 Bindings In this subsection, we study the inhibitors S43, GRL0617, and XR8-89 binding to SARS-CoV-2-PLpro-dimer, JUN9-84-3, and JUN9-72-2 binding to SARS-CoV2-PLpro-trimer, respectively. The five models (1) C112S-mutant dimer bound to compound S43 (7E35.pdb), (2) wt dimer in complex with inhibitor GRL0617 (7JRN.pdb), (3) wt dimer in complex with inhibitor XR8-89 (7LBR.pdb), (4) wt trimer in complex with inhibitor JUN9-84-3 (7RZC.pdb), and (5) wt trimer in complex with inhibitor JUN9-72-2 (7SDR.pdb) are based on PDB entries 7E35, 7JRN, 7LBR, 7RZC, 7SDR respectively. We optimized the five models and the optimized models have RMSD values 0.545701, 0.453181, 0.441584, 0.477715, and 0.473589 Å, respectively, from the original models. The .π -interactions of the optimized five models are (1) 7E35-PLpro-C112S-S43-dimer ◦ .π -cations A:LYS218.NZ.+-A:TYR311, B:LYS93.NZ.+-B:HID90, ◦ .π -.π stackings A:TYR72-A:TYR73, A:PHE128-A:TYR137, A:TYR265A:TYR274, B:TYR72-B:TYR73-B:PHE80, B:PHE128-B:TYR137, B:PHE174-B:PHE242
. .
(2) 7JRN-PLpro-wt-GRL0617-dimer ◦ .π -cations A:LYS217.NZ.+-A:TYR310, J:LYS92.NZ.+-J:HID89, J:LYS217. NZ.+-J:TYR310, .◦ .π -.π stackings A:TYR71-A:TYR72, A:TYR264-A:TYR273, J:TYR71J:TYR72-J:PHE79, J:TYR264-J:TYR273, J:TYR207-J:PHE216 .
(3) 7LBR-PLpro-wt-XR8-89-dimer ◦ .π -cations A:LYS92.NZ.+-A:HID89, -A:TYR213, B:LYS92.NZ.+-B:HID89,
.
A:TYR310-A:LYS217.NZ.+
1.4 Concluding Remarks
11
◦ .π -.π stackings A:TYR71-A:TYR72-A:PHE79, A:PHE127-A:TYR136, A:TYR207-A:PHE216, B:TYR71-B:TYR72-B:PHE79, B:TYR207B:PHE216
.
(4) 7RZC-PLpro-wt-Jun9-84-3-trimer ◦ .π -cations A:LYS92.NZ.+-A:HID89, A:LYS217.NZ.+-A:TYR310, B:LYS92.NZ.+-B:HID89, .◦ .π -.π stackings A:TYR71-A:TYR72, A:TYR154-A:HID175, B:TYR71B:TYR72, B:TYR136-B:TYR137, B:TYR264-B:TYR273, C:TYR71C:TYR72, C:TYR207-C:PHE216 .
(5) 7SDR-PLpro-wt-Jun9-72-2-trimer ◦ .π -cations A:LYS217.NZ.+-A:TYR310, B:LYS217.NZ.+-B:TYR310, B:LYS92.NZ.+-B:HID89, C:LYS92.NZ.+-C:HID89, .◦ .π -.π stackings A:TYR71-A:TYR72, B:TYR71-B:TYR72, B:TYR136B:TYR137, C:TYR71-C:TYR72, C:TYR207-C:PHE216 .
where we can see .π -cation LYS92.NZ.+-HID89 and .π -.π stacking TYR71-TYR72 are always there (Fig. 1.12). The SBs and HBs of the five models optimized are listed in Tables 1.11, 1.12, and 1.13. All the residues of the optimized models of (1) 7E35PLpro-C112S-S43-dimer, (2) 7JRN-PLpro-wt-GRL0617-dimer, (3) 7LBR-PLprowt-XR8-89-dimer, (4) 7RZC-PLpro-wt-Jun9-84-3-trimer, and (5) 7SDR-PLpro-wtJun9-72-2-trimer that bind with the ions Zn2.+ and their respective inhibitors are listed in Table 1.14, where we can see the binding sites are almost the same for the five models. We also find for the dimer models (2)–(3) around residues HIS73THR75 and ASN128-PRO129 there is a large area of negative charge EPS, and for the trimer models (4)–(5) their .β-sheets have a large area of positive charge EPS (Fig. 1.13). All the above observations may be confirmed by the three sets of MD databases of each model [283].
1.4 Concluding Remarks In conclusion, for PLpro in this brief chapter, we found some interesting preliminary results such as (1) the polar contacts ASP76-ARG82 and ASP286-HIS272 are very important for keeping the monomer structure stable, (2) the broken of salt bridge GLU307-LYS217 might lead to some motion in the C-terminal residues, and (3) for the dimer, the polar contacts GLU143-ARG138 (in Mpro-dimer the SBs GLU290ARG4 linking its two monomers (Chap. 2)) and HBs ARG140.H-TYR137.OH make the two monomers (of a dimer) linking to each other, etc. For the SARSCoV-2-PLpro C111S mutant, the SB GLU67-HIS17 cannot be maintained during MD simulation because of ion ZN503. Comparisons with SARS-VoV-2-PLpro and the binding sites for inhibitors S43, GRL0617, XR8-89, JUN9-84-3, and JUN9-72-2 are also studied in this chapter.
12
1 Papain-Like Cysteine Protease (PLpro)
Supplementary Information
Fig. 1.9 Other SBs from the analyses of the MD trajectory data of [321]
Supplementary Information
Fig. 1.9 (continued)
13
14
1 Papain-Like Cysteine Protease (PLpro)
Fig. 1.10 HBs GLU307.N-PRO240.O (21.48%), THR311-GLU307 (N-O 14.69%, OG1-O 10.09%), and TYR310.N-GLU307.O (5.79%)
Table 1.1 The HBs with more than 30% occupancy rates from the analyses of the 100 μs’ MD trajectory data of [321]
Donor
Acceptor
Occupancy
PHE173-Main-N
MET169-Main-O
71.53%
MET243-Main-N
VAL205-Main-O
67.13%
LYS105-Main-N
LYS94-Main-O
66.73%
MET244-Main-N
VAL303-Main-O
66.63%
MET169-Main-N
VAL165-Main-O
66.53%
TYR83-Main-N
PHE79-Main-O
64.64%
PHE304-Main-N
CYS260-Main-O
64.54%
LEU117-Main-N
LEU113-Main-O
63.94%
PHE55-Main-N
PHE8-Main-O
63.74%
LEU199-Main-N
ARG183-Main-O
63.54%
ASP22-Main-N
GLN30-Side-OE1
62.24%
ILE285-Main-N
HIS275-Main-O
61.94%
TYR154-Main-N
LEU150-Main-O
61.44%
MET84-Main-N
LEU80-Main-O
61.04%
PHE31-Main-N
TYR27-Main-O
60.44%
VAL7-Main-N
GLN19-Main-O
60.14%
LEU120-Main-N
ALA116-Main-O
59.44%
LYS232-Main-N
VAL220-Main-O
56.04%
TYR154-Side-OH
TYR72-Main-O
55.84%
LEU87-Main-N
TYR83-Main-O
53.85%
TYR95-Side-OH
THR90-Main-O
53.35%
TYR305-Side-OH
LEU211-Main-O
52.75%
ASN128-Main-N
HIS175-Main-O
52.65%
ILE276-Main-N
ALA261-Main-O
52.45%
ILE151-Main-N
PHE147-Main-O
52.05%
GLY209-Main-N
SER245-Main-O
51.95%
ALA230-Main-N
ILE222-Main-O
51.35%
CYS284-Main-N
THR291-Main-O
51.15%
GLN237-Side-NE2
ALA204-Main-O
49.75%
TYR72-Side-OH
VAL11-Main-O
49.45%
ARG183-Side-NE
GLN237-Side-OE1
49.25%
THR34-Side-OG1
GLY32-Main-O
48.95%
GLN121-Side-NE2
LEU117-Main-O
48.55%
(continued)
Supplementary Information Table 1.1 (continued)
15 Donor
Acceptor
Occupancy
VAL188-Main-N
THR231-Main-O
48.25%
THR168-Side-OG1
ASP164-Main-O
48.15%
VAL220-Main-N
LYS232-Main-O
47.65%
ILE222-Main-N
ALA230-Main-O
47.45%
THR102-Main-N
GLN121-Side-OE1
46.65%
ARG140-Main-N
TYR136-Main-O
46.55%
VAL303-Main-N
MET244-Main-O
46.35%
TYR35-Main-N
TYR56-Main-O
46.15%
PHE69-Main-N
ARG65-Main-O
45.65%
SER103-Main-N
PRO96-Main-O
45.55%
ASP134-Main-N
PRO130-Main-O
44.76%
GLN19-Main-N
VAL7-Main-O
44.06%
SER85-Main-N
GLY81-Main-O
43.76%
VAL98-Main-N
LEU101-Main-O
43.66%
ARG65-Side-NE
PRO59-Main-O
43.46%
LEU150-Main-N
ASN146-Main-O
43.26%
THR10-Side-OG1
ASN15-Main-O
43.06%
GLY52-Main-N
LYS6-Main-O
42.86%
GLY219-Main-N
GLN215-Main-O
42.76%
THR119-Side-OG1
THR115-Main-O
42.56%
THR277-Main-N
TYR283-Main-O
42.26%
ALA139-Main-N
ALA135-Main-O
40.96%
THR301-Main-N
SER262-Main-O
40.76%
ASN177-Main-N
LYS126-Main-O
40.66%
GLN121-Side-NE2
THR102-Main-O
40.46%
GLU263-Main-N
LYS274-Main-O
40.46%
VAL184-Main-N
GLN236-Main-O
40.36%
ASP286-Main-N
LEU289-Main-O
40.06%
TYR251-Main-N
GLY298-Main-O
39.16%
CYS148-Main-N
ALA144-Main-O
39.16%
LEU36-Main-N
ALA39-Main-O
38.96%
SER239-Side-OG
PHE241-Main-O
38.56%
TYR233-Main-N
ASN186-Main-O
38.36%
LEU185-Main-N
THR197-Main-O
38.26%
TYR283-Main-N
THR277-Main-O
38.26%
THR90-Main-N
ALA86-Main-O
38.26%
LYS217-Main-N
TYR213-Main-O
37.26%
ASN110-Side-ND2
LYS105-Main-O
36.96%
TYR264-Main-N
PRO299-Main-O
36.56%
TYR72-Main-N
ALA68-Main-O
35.86%
LEU118-Main-N
ALA114-Main-O
35.56%
CYS155-Main-N
ILE151-Main-O
35.46%
THR259-Main-N
PHE304-Main-O
34.57%
THR197-Main-N
LEU185-Main-O
33.97%
GLN215-Main-N
SER212-Side-OG
33.47%
LYS91-Main-N
LEU87-Main-O
33.37%
ALA114-Main-N
ASN110-Main-O
32.77%
GLU70-Main-N
VAL66-Main-O
32.57%
LYS157-Side-NZ
LEU162-Main-O
32.27%
HIS175-Side-ND1
TYR171-Main-O
32.17%
LYS157-Main-N
LEU152-Main-O
32.07%
THR9-Main-N
HIS17-Main-O
31.97%
THR90-Side-OG1
ALA145-Main-O
31.87%
HIS17-Main-N
THR9-Main-O
31.57%
ASN267-Main-N
CYS270-Main-O
31.47%
TYR296-Side-OH
GLU263-Side-OE2
31.27%
ILE123-Main-N
THR119-Main-O
31.27%
VAL21-Main-N
ILE5-Main-O
30.97%
PHE8-Main-N
LYS53-Main-O
30.97%
THR115-Main-N
CYS111-Main-O
30.97%
TYR56-Main-N
TYR35-Main-O
30.67%
TYR305-Main-N
VAL242-Main-O
30.57%
TYR264-Side-OH
ASN267-Main-O
30.37%
TYR171-Main-N
GLU167-Main-O
30.37%
ALA131-Main-N
TYR71-Main-O
30.07%
Table 1.2 The HBs (with more than 5% occupancy rates) of the SARS-CoV-2-PLpro C111S mutant from the analyses of the 1604 frames’ supervised MD trajectory data (Concat-UnbindingSuMD-7JIT-rep1-fit-fit.xtc) of [332] TYR213.OH-GLU307.OE1 82.67%
GLY209.N-SER245.O 41.02%
SER24.N-ASP22.OD1 25.37%
TRP93.NE1-ASP108.OD1 12.16%
HIS272.NE2-ASP286.OD1 74.31%
LEU87.N-TYR83.O 40.84%
THR42.OG1-ASP40.OD1 25.25%
GLU143.N-ARG138.O 11.66%
ASN15.N-ASP12.OD1 72.44%
ARG82.N-SER78.O 40.34%
LEU117.N-LEU113.O 24.88%
GLU70.N-VAL66.O 11.66%
SER245.OG-ASP302.OD1 71.82%
GLN19.N-VAL7.O 39.78%
HIS50.N-HIS47.O 24.69%
THR119.N-THR115.O 11.47%
TYR283.OH-GLU280.OE2 70.32%
LEU118.N-ALA114.O 39.59%
ALA261.N-ILE276.O 24.56%
ARG140.NH1-GLU124.OE1 11.28%
PHE304.N-CYS260.O 64.90%
HIS255.NE2-LYS279.O 39.21%
SER245.N-TYR207.O 24.25%
THR168.N-ASP164.O 11.03%
TYR95.OH-THR90.O 63.72%
LYS105.N-LYS94.O 39.03%
HIS272.N-THR265.O 24.00%
LYS274.N-GLU263.O 10.85%
GLN237.NE2-ALA204.O 62.28%
THR301.N-SER262.O 38.65%
ARG140.NH2-GLU124.OE2 23.75%
ASN88.N-MET84.O 10.66%
TYR296.OH-GLU263.OE2 61.41%
LYS217.NZ-GLU214.OE1 38.40%
CYS155.N-ILE151.O 23.63%
CYS181.N-LEU178.O 10.66%
TYR305.OH-LEU211.O 61.35%
MET169.N-VAL165.O 38.03%
ARG138.NH2-GLU143.OE2 23.50%
ARG138.NH1-ASP134.OD2 10.66%
THR63.OG1-ASP61.OD2 59.73%
TYR83.N-PHE79.O 37.97%
THR291.N-CYS284.O 23.32%
MET206.N-VAL202.O 10.60%
THR168.OG1-ASP164.O 59.10%
LYS279.N-THR281.O 37.22%
GLU167.N-ASP164.OD1 23.07%
ASN60.ND2-LEU58.O 10.41%
VAL188.N-THR231.O 58.85%
HIS275.NE2-GLN122.OE1 36.85%
THR90.N-ALA86.O 22.76%
LYS91.N-LEU87.O 10.35%
LEU253.N-TYR296.O 58.29%
ASP134.N-PRO130.O 36.78%
LYS200.NZ-ASP179.OD1 22.63%
TYR27.N-ILE44.O 10.22%
MET243.N-VAL205.O 57.61%
LYS182.N-GLU238.O 36.41%
ALA116.N-TYR112.O 22.44%
ASN13.N-THR10.OG1 10.16%
VAL98.N-LEU101.O 56.42%
CYS148.N-ALA144.O 36.28%
GLN237.N-TYR310.O 22.38%
TYR296.N-LEU253.O 10.10%
ASN308.N-GLU307.OE2 56.17%
ASP286.N-LEU289.O 36.03%
TYR264.OH-ASN267.O 22.38%
LYS157.NZ-GLU167.OE1 9.98%
GLN121.NE2-LEU117.O 55.92%
SER239.OG-PHE241.O 36.03%
SER293.OG-GLU295.O 22.26%
ARG140.NH1-GLU124.OE2 9.73%
ALA230.N-ILE222.O 55.86%
THR231.N-VAL188.O 35.97%
VAL242.N-TYR305.O 22.19%
LYS157.NZ-LEU162.O 9.60%
TYR72.OH-VAL11.O 55.30%
GLU263.N-LYS274.O 35.85%
GLY227.N-CYS224.O 22.19%
TYR112.OH-GLU161.O 9.60%
ILE285.N-HIS275.O 54.74%
SER85.N-GLY81.O 35.79%
ALA68.N-LEU64.O 22.07%
VAL205.N-VAL202.O 9.29%
TRP93.NE1-ASP108.OD2 54.55%
ARG138.NH2-GLU143.OE1 35.54%
GLN97.NE2-THR102.OG1 21.70%
GLN221.NE2-THR231.OG1 9.29%
MET244.N-VAL303.O 54.49%
SER262.N-ASP302.O 35.54%
ALA139.N-ALA135.O 21.51%
HIS89.NE2-ASP108.OD1 9.23%
LEU36.N-ALA39.O 54.11%
ALA114.N-ASN110.O 35.54%
TYR233.N-ASN186.O 21.45%
GLN122.N-THR119.O 9.16%
TYR35.N-TYR56.O 53.93%
SER78.OG-ASP76.OD1 35.41%
SER78.OG-ASP76.OD2 20.95%
TYR268.N-ASN267.OD1 9.10%
GLY219.N-GLN215.O 53.49%
ASN15.ND2-ASP12.OD2 35.41%
TYR83.OH-ASN146.OD1 20.57%
ARG166.NE-ASP302.OD1 9.10%
TYR305.N-VAL242.O 53.49%
THR197.N-LEU185.O 35.22%
LEU152.N-CYS148.O 20.51%
HIS89.NE2-ASP108.OD2 8.79%
PHE127.N-GLN133.OE1 52.56%
VAL235.N-VAL184.O 34.85%
LEU234.N-PHE216.O 20.32%
LYS92.NZ-ASP108.OD2 8.73%
SER24.OG-ASP22.OD1 52.43%
TYR27.OH-HIS50.ND1 34.79%
THR115.N-SER111.O 20.26%
HIS275.N-ILE285.O 8.60%
GLN237.NE2-SER239.OG 52.37%
VAL220.N-LYS232.O 34.79%
PHE31.N-TYR27.O 19.89%
GLN215.N-SER212.OG 7.86%
LEU199.N-ARG183.O 51.87%
TYR56.OH-TYR72.OH 34.54%
GLY256.N-SER278.OG 19.83%
GLN174.NE2-SER170.O 7.86%
CYS284.N-THR291.O 50.94%
THR34.N-THR42.OG1 33.98%
LYS254.NZ-GLU295.OE1 19.51%
GLY201.N-CYS181.O 7.73%
ILE276.N-ALA261.O 50.87%
GLU238.N-LYS182.O 33.60%
LYS254.NZ-GLU252.OE1 19.45%
LYS91.NZ-ASP37.O 7.67%
TYR56.N-TYR35.O 50.25%
THR257.OG1-LYS254.O 32.42%
THR90.OG1-ALA86.O 19.20%
ALA86.N-ARG82.O 7.42%
THR119.OG1-THR115.O 50.19%
VAL184.N-GLN236.O 32.11%
THR265.OG1-GLU263.OE1 19.14%
HIS47.N-HIS50.ND1 7.36%
TYR154.OH-TYR72.O 49.50%
ARG183.NH1-MET206.O 32.04%
THR312.N-VAL235.O 18.70%
TYR71.OH-ASP134.OD2 7.29%
TYR283.N-THR277.O 49.19%
HIS17.N-THR9.O 31.92%
LYS254.NZ-GLU252.OE2 18.39%
ARG65.N-ASP61.O 7.23%
ASN177.N-LYS126.O 49.19%
SER309.OG-GLU238.OE2 30.74%
ARG138.NE-GLU143.OE1 18.20%
LEU162.N-GLU161.OE2 7.11%
TYR264.N-PRO299.O 48.75%
PHE55.N-PHE8.O 30.67%
ALA149.N-ALA145.O 17.89%
THR63.N-ASP61.OD1 7.04%
GLY193.N-CYS189.O 48.32%
ASN186.N-TYR233.O 30.49%
SER85.OG-GLY81.O 17.64%
GLY81.N-SER78.O 7.04%
VAL7.N-GLN19.O 48.19%
HIS175.ND1-TYR171.O 29.80%
TYR251.N-GLY298.O 17.21%
SER111.OG-ASN109.OD1 7.04%
SER103.N-PRO96.O 48.19%
ALA246.N-THR301.O 29.61%
SER170.N-ARG166.O 17.14%
THR231.OG1-GLN221.OE1 6.98%
THR277.N-TYR283.O 47.69%
LYS254.NZ-GLU295.OE2 29.05%
ILE5.N-VAL21.O 16.96%
ALA249.N-ILE300.O 6.92%
ASN128.N-HIS175.O 46.95%
LEU120.N-ALA116.O 28.99%
THR42.N-ASP40.OD2 16.96%
ARG140.N-TYR136.O 6.61%
TYR154.N-LEU150.O 46.88%
THR277.OG1-GLN122.OE1 28.87%
GLN215.NE2-GLY219.O 16.90%
ASN186.ND2-GLN196.OE1 6.61%
PHE173.N-MET169.O 46.45%
THR259.N-PHE304.O 28.43%
LEU150.N-ASN146.O 16.27%
LEU172.N-THR168.O 6.36%
THR9.N-HIS17.O 46.38%
PHE69.N-ARG65.O 27.93%
SER278.N-THR259.O 16.21%
GLU167.N-ASP164.OD2 6.30%
SER103.OG-GLY287.O 46.38%
LYS200.NZ-ASP179.OD2 27.81%
LYS279.NZ-ASN99.OD1 15.90%
PHE8.N-LYS53.O 6.23%
GLN121.NE2-THR102.O 46.13%
THR34.OG1-GLY32.O 27.81%
THR42.N-ASP40.OD1 15.77%
ASN177.ND2-ASN128.OD1 6.23%
VAL303.N-MET244.O 45.64%
ARG183.N-LEU199.O 27.68%
LYS91.NZ-ASP37.OD2 15.59%
ARG166.NH2-ASP302.OD2 6.23%
ARG183.NE-GLN237.OE1 45.20%
THR42.OG1-ASP40.OD2 27.68%
SER170.OG-ARG166.O 15.52%
LYS53.N-HIS50.O 6.05%
ARG82.NE-SER78.OG 44.70%
CYS224.N-LYS228.O 27.49%
LYS217.NZ-GLU214.OE2 15.27%
LYS157.NZ-GLU161.OE1 5.99%
THR301.OG1-ALA246.O 44.45%
ASN146.ND2-TYR83.OH 27.31%
THR63.OG1-ASP61.OD1 15.15%
ARG65.NH1-ASP62.OD1 5.99%
LYS232.N-VAL220.O 44.26%
THR102.OG1-ALA139.O 27.18%
THR9.OG1-HIS17.O 14.40%
TYR171.N-GLU167.O 5.92%
TYR72.N-ALA68.O 44.01%
THR63.N-ASP61.OD2 27.12%
VAL165.N-TYR273.OH 14.21%
GLN122.NE2-THR277.OG1 5.80%
ASN110.ND2-LYS105.O 43.95%
CYS192.N-CYS189.O 27.12%
ASN186.ND2-GLN194.OE1 14.21%
LYS92.N-HIS89.O 5.74%
THR102.N-GLN121.OE1 43.70%
MET23.N-ARG3.O 27.06%
ASN186.ND2-TYR233.OH 14.21%
LEU101.N-VAL98.O 5.61%
ARG82.NH2-ASP76.OD2 43.52%
SER293.N-LEU282.O 26.87%
TYR136.N-LEU132.O 13.72%
SER78.N-ASP76.OD1 5.49%
LEU185.N-THR197.O 43.27%
ARG140.NH2-GLU124.OE1 26.87%
THR277.OG1-THR259.O 13.65%
HIS89.N-ALA86.O 5.42%
VAL21.N-ILE5.O 43.20%
CYS189.N-GLY193.O 26.81%
THR90.OG1-ALA145.O 13.59%
ASN15.ND2-ASP12.OD1 5.42%
TYR136.OH-LEU120.O 43.08%
ARG138.NE-GLU143.OE2 26.62%
GLU307.N-PRO240.O 13.28%
ARG140.NH2-TYR136.OH 5.42%
ILE222.N-ALA230.O 42.96%
SER24.OG-ASP22.OD2 26.50%
GLN195.N-VAL187.O 13.28%
ALA131.N-TYR71.O 5.30%
TYR310.N-GLN237.O 42.39%
SER309.OG-GLU238.OE1 26.43%
LYS91.NZ-ASP37.OD1 13.28%
SER49.N-HIS47.ND1 5.17%
LYS274.NZ-GLU263.OE1 42.39%
ARG82.NH1-ALA153.O 26.43%
SER24.N-ASP22.OD2 13.28%
CYS270.N-ASN267.O 5.11%
VAL41.N-THR34.O 42.33%
ARG82.NH2-ASP76.OD1 26.18%
LYS279.NZ-GLU280.OE1 13.15%
THR231.OG1-VAL220.O 5.11%
THR115.OG1-SER111.O 42.02%
ILE14.N-ASP12.OD1 26.06%
GLU280.N-GLU280.OE1 12.91%
TYR283.OH-GLU280.OE1 5.05%
VAL187.N-GLN195.O 41.40%
ILE151.N-PHE147.O 26.06%
SER49.OG-HIS47.ND1 12.84%
THR10.OG1-ASN15.O 41.27%
LYS157.N-LEU152.O 25.37%
GLN133.NE2-TYR137.OH 12.28%
Supplementary Information
17
Table 1.3 All the SBs of the five PLpro models in http://chemcha-gpu0.ucr.edu/software/ optimized (1) SARS-CoV-2-wt
(4) SARS-CoV-1-wt
(3) SARS-CoV-2-wt-S88
(5) SARS-CoV-1-wt-S88
(2) SARS-CoV-2-C111S-mutant
ASP37-LYS91 ASP40-LYS43
ASP41-LYS44
ASP40-LYS43
ASP41-LYS44 GLU52-LYS7
GLU51-LYS6
ASP61-HIS17 ASP62-ARG65
ASP62-ARG65 GLU68-HIS18
GLU68-HIS18 ASP76-ARG82
ASP77-ARG83
ASP77-ARG83
ASP76-ARG82
GLU78-ARG66
GLU78-ARG66 ASP108-HIS89 ASP108-LYS92 GLU124-LYS126
GLU124-LYS126 GLU125-LYS307
GLU124-LYS126 GLU125-LYS307 GLU143-ARG138
ASP134-ARG138
GLU135-ARG139
GLU143-ARG138
ASP144-ARG139
ASP134-ARG138
GLU161-LYS157
GLU162-LYS158
GLU161-LYS157
GLU162-LYS158
ASP164-ARG166
ASP165-ARG167
ASP164-ARG166
ASP165-ARG167
ASP144-ARG139 GLU161-LYS157
GLU167-LYS157 GLU167-ARG166 GLU168-ARG167
GLU168-ARG167
GLU180-LYS127
GLU180-LYS127
ASP179-LYS200 GLU214-LYS217
ASP215-LYS218
GLU214-LYS218
ASP215-LYS218
GLU214-LYS217
GLU214-LYS218 ASP230-ARG229 ASP230-LYS191 GLU238-LYS182
GLU239-LYS183
GLU238-LYS182
GLU251-LYS298
GLU239-LYS183
GLU252-LYS254
GLU252-LYS297
GLU252-LYS297
GLU263-LYS274
GLU263-LYS274 GLU264-ARG285
GLU263-LYS274 GLU264-ARG285 GLU281-LYS280
GLU280-LYS279 GLU281-LYS293 ASP286-HIS272
GLU238-LYS182
GLU251-LYS298 GLU252-LYS254
ASP287-HIS273
GLU280-LYS279
GLU281-LYS293 ASP286-HIS272
ASP287-ARG285
ASP287-HIS273
ASP286-HIS272
ASP287-ARG285
GLU296-LYS253 GLU295-LYS254
GLU295-LYS254
ASP302-ARG166 GLU307-LYS217
18
1 Papain-Like Cysteine Protease (PLpro)
Table 1.4 All the SBs of the five PLpro models in http://chemcha-gpu0.ucr.edu/software/ during 1 μs’ MDs (1) SARS-CoV-2-wt
(4) SARS-CoV-1-wt
(3) SARS-CoV-2-wt-S88
(5) SARS-CoV-1-wt-S88
(2) SARS-CoV-2-C111S-mutant
ASP37-LYS53
ASP38-LYS54
ASP37-LYS53
ASP38-LYS54
ASP37-LYS53
ASP37-LYS91
ASP38-LYS92
ASP37-LYS91
ASP38-LYS92
ASP37-LYS91
ASP37-ARG138 ASP40-LYS43
ASP41-LYS44
ASP40-LYS43
ASP41-LYS44
ASP40-LYS43
GLU51-LYS6
GLU52-LYS4
GLU51-LYS6
GLU52-LYS7
GLU51-LYS6
GLU52-LYS7 ASP61-ARG65 ASP62-ARG65
ASP63-ARG66
ASP62-ARG65
ASP63-ARG66
ASP62-ARG65
ASP76-ARG82
ASP77-ARG83
ASP76-ARG82
ASP77-ARG83
ASP76-ARG82
GLU78-ARG66
GLU78-ARG66
ASP108-LYS92
ASP109-LYS93
ASP108-LYS92
ASP109-LYS93
ASP108-LYS92
GLU124-ARG140
GLU125-ARG141
GLU124-ARG140
GLU125-ARG141
GLU124-ARG140
GLU124-LYS126
GLU125-LYS127
GLU124-LYS126
GLU125-LYS127
GLU124-LYS126
GLU124-LYS279
GLU125-LYS280
GLU124-LYS279
GLU125-LYS280
GLU124-LYS279
GLU124-LYS306
GLU125-LYS307
GLU124-LYS306
GLU125-LYS307
GLU124-LYS306
ASP134-ARG138
GLU135-ARG139
ASP134-ARG138
GLU135-ARG139
ASP134-ARG138
GLU143-LYS91
ASP144-LYS92
GLU143-LYS91
ASP144-LYS92
GLU143-LYS91
GLU143-ARG138
ASP144-ARG139
GLU143-ARG138
ASP144-ARG139
GLU143-ARG138
GLU161-LYS157
GLU162-LYS158
GLU161-LYS157
GLU162-LYS158
GLU161-LYS157
ASP164-ARG166
ASP165-ARG167
ASP164-ARG166
ASP165-ARG167
ASP164-ARG166
ASP164-LYS157 GLU167-LYS157
GLU168-LYS158
GLU167-LYS157
GLU168-LYS158
GLU168-ARG167
GLU167-ARG166
GLU168-ARG167
GLU167-LYS157 GLU167-ARG166 ASP179-LYS126
GLU180-LYS127 GLU180-LYS183 ASP179-LYS200 GLU214-LYS217
ASP179-LYS200 ASP215-LYS218
GLU214-LYS218
GLU214-LYS217
ASP179-LYS200 ASP215-LYS218
GLU214-LYS218
GLU214-LYS217 GLU214-LYS218
GLU214-LYS254 GLU214-LYS315
GLU214-LYS315 ASP230-LYS191
ASP230-LYS191
ASP230-ARG229 GLU238-LYS182
GLU239-LYS183
ASP230-ARG229 GLU238-LYS182
GLU239-LYS183
GLU238-LYS182
GLU238-LYS315 GLU251-LYS253 GLU251-LYS298
GLU251-LYS298
GLU252-LYS254
GLU252-LYS254
GLU252-LYS297
GLU252-LYS297
GLU252-LYS297
GLU263-LYS274
GLU263-LYS274
GLU263-LYS274
GLU264-ARG285 GLU280-LYS279
GLU281-LYS280
GLU280-LYS292
GLU281-LYS293
ASP286-LYS274
ASP287-ARG285
GLU252-LYS254
GLU264-ARG285 GLU280-LYS279
GLU281-LYS280
GLU280-LYS279 GLU280-LYS292
GLU281-LYS307 ASP286-LYS274
GLU296-LYS253
ASP287-ARG285
GLU295-LYS254
GLU295-LYS254
ASP286-LYS274
GLU296-LYS253 GLU295-LYS254
GLU295-LYS297
GLU296-LYS298
GLU295-LYS297
ASP302-ARG166
ASP303-ARG167
ASP302-ARG166
GLU307-LYS217
GLU308-LYS218
GLU307-LYS217
GLU308-LYS218
GLU308-LYS307
GLU307-LYS306
GLU308-LYS307
GLU296-LYS298
GLU295-LYS297 ASP302-ARG166 GLU307-LYS217
Supplementary Information
19
Table 1.5 All the HBs of the five PLpro models in http://chemcha-gpu0.ucr.edu/software/ optimized (1) SARS-CoV-2-wt
(4) SARS-CoV-1-wt
(3) SARS-CoV-2-wt-S88
(5) SARS-CoV-1-wt-S88
(2) SARS-CoV-2-C111S-mutant
THR4.N-ASP22.OD1
THR5.OG1-VAL22.O
ILE5.N-VAL21.O
LYS7.N-GLU52.OE1
THR4.N-ASP22.OD1
LYS6.N-GLU51.OE2
LYS7.N-GLU52.OE2
LYS6.N-GLU51.OE1
LYS7.NZ-GLU52.OE2
LYS6.N-GLU51.OE2
VAL7.N-GLN19.O
VAL8.N-GLN20.O
VAL7.N-GLN19.O
PHE9.N-LYS54.O
LYS6.NZ-GLU51.OE1
PHE8.N-LYS53.O
THR10.OG1-HIS18.O
PHE8.N-LYS53.O
THR10.N-HIS18.O
ILE14.N-ASP12.OD1
THR9.N-HIS17.O
THR15.N-ASP13.OD1
THR9.N-HIS17.O
THR10.OG1-HIS18.O
ASN15.ND2-ASP12.OD2
THR9.OG1-HIS17.O
ASN16.N-ASP13.OD1
ILE14.N-ASP12.OD2
THR15.N-ASP13.OD1
GLN19.N-VAL7.O
ILE14.N-ASP12.OD1
ASN16.ND2-ASP13.OD2
ASN15.N-ASP12.OD2
ASN16.ND2-ASP13.OD2
VAL21.N-ILE5.O
ASN15.ND2-ASP12.OD2
HIS18.NE2-GLU68.OE2
ASN15.ND2-ASP12.OD1
HIS18.NE2-GLU68.OE2
ASP22.N-GLN30.OE1
GLN19.N-VAL7.O
GLN20.N-VAL8.O
THR18.OG1-VAL7.O
GLN20.N-VAL8.O
SER24.N-ASP22.OD2
ASP22.N-GLN30.OE1
VAL22.N-ILE6.O
VAL21.N-ILE5.O
VAL22.N-ILE6.O
SER24.OG-ASP22.OD2
SER24.N-ASP22.OD2
ASP23.N-GLN31.OE1
SER24.N-ASP22.OD2
SER25.OG-ASP23.OD2
THR26.N-GLN29.OE1
THR26.N-GLN29.OE1
MET26.N-ASP23.OD2
SER24.OG-ASP22.OD1
MET26.N-ASP23.OD1
TYR27.OH-HIS50.ND1
TYR27.OH-HIS50.ND1
TYR28.N-ILE45.O
THR26.N-GLN29.OE1
TYR28.N-ILE45.O
GLN30.NE2-THR26.O
GLN30.NE2-THR26.O
TYR28.OH-HIS51.ND1
THR26.OG1-GLN29.OE1
TYR28.OH-HIS51.ND1
PHE31.N-TYR27.O
PHE31.N-TYR27.O
GLN31.NE2-ASP23.O
TYR27.N-ILE44.O
GLN31.NE2-ASP23.O
THR34.OG1-GLY32.O
THR34.OG1-GLY32.O
PHE32.N-TYR28.O
TYR27.OH-HIS50.ND1
PHE32.N-TYR28.O
THR34.N-THR42.OG1
THR34.N-THR42.OG1
GLY33.N-TYR28.O
GLN29.N-THR26.O
THR35.OG1-GLY33.O
TYR35.N-TYR56.O
TYR35.N-TYR56.O
THR35.N-THR43.OG1
PHE31.N-TYR27.O
THR35.N-THR43.OG1
THR42.N-ASP40.OD1
LEU36.N-ALA39.O
THR35.OG1-GLY33.O
GLY32.N-TYR27.O
LEU37.N-ALA40.O
LYS45.NZ-SER24.O
ASP40.OD1-LYS43.NZ
TYR36.N-PHE57.O
THR34.OG1-GLY32.O
ASP41.OD2-LYS44.NZ
HIS50.N-HIS47.O
VAL41.N-THR34.O
ALA40.N-LEU37.O
TYR35.N-TYR56.O
VAL42.N-THR35.O
GLU51.OE1-LYS6.NZ
LYS43.NZ-ASP40.OD1
ASP41.OD2-LYS44.NZ
LEU36.N-ALA39.O
LYS44.NZ-ASP41.OD2
LYS53.NZ-SER49.O
SER49.OG-HIS47.ND1
VAL42.N-THR35.O
ASP37.OD1-LYS91.NZ
LYS46.NZ-SER25.O
TYR56.N-TYR35.O
HIS50.N-HIS47.O
THR43.N-ASP41.OD1
ASP40.OD1-LYS43.NZ
GLU52.OE2-LYS7.NZ
ASN60.ND2-PHE31.O
GLY52.N-LYS6.O
LYS44.NZ-ASP41.OD2
VAL41.N-THR34.O
GLY53.N-LYS7.O
ASP62.OD1-ARG65.NH2
LYS53.NZ-SER49.O
LYS46.NZ-SER25.O
THR42.N-ASP40.OD2
LYS54.N-HIS51.O
THR63.OG1-ASP61.OD2
PHE55.N-PHE8.O
GLY53.N-LYS7.O
LYS43.NZ-ASP40.OD1
PHE56.N-PHE9.O
ARG65.NE-ASP62.OD2
THR63.N-ASP61.OD2
PHE56.N-PHE9.O
LYS45.NZ-SER24.O
VAL58.N-THR11.O
ARG65.NH2-ASP62.OD1
LEU64.N-ASP61.OD1
VAL58.N-THR11.O
SER49.OG-HIS47.ND1
THR64.N-ASP62.OD2
GLU70.N-VAL66.O
ARG65.NH1-ASN60.O
THR64.OG1-ASP62.OD1
HIS50.N-HIS47.O
THR64.OG1-ASP62.OD2
TYR72.OH-VAL11.O
GLU67.N-THR63.O
ARG66.NE-SER61.O
GLY52.N-LYS6.O
LEU65.N-ASP62.OD1
TYR72.N-ALA68.O
GLU70.N-VAL66.O
ARG66.NH1-GLU78.OE1
LYS53.NZ-SER49.O
ARG66.NE-SER61.O
ASP76.OD2-ARG82.NH2
TYR71.OH-ASP134.OD1
ARG66.NH2-GLU78.OE2
PHE55.N-PHE8.O
ARG66.NH1-GLU78.OE1
SER78.OG-ASP76.OD1
TYR72.N-ALA68.O
SER67.OG-ASP63.O
TYR56.N-TYR35.O
ARG66.NH2-GLU78.OE2
ARG82.NH2-ASP76.OD2
TYR72.OH-VAL11.O
GLU68.N-THR64.O
TYR56.OH-TYR72.OH
GLU68.OE2-HIS18.NE2
ARG82.NH1-ALA153.O
ASP76.OD2-ARG82.NH1
ALA69.N-LEU65.O
LEU64.N-ASP62.O
TYR72.OH-GLU135.OE1
TYR83.N-PHE79.O
SER78.OG-ASP76.OD1
GLU71.N-SER67.O
ARG65.NH1-PRO59.O
TYR73.OH-VAL12.O
MET84.N-LEU80.O
ARG82.NH1-ASP76.OD2
TYR72.OH-GLU135.OE1
VAL66.N-ASP62.O
TYR73.N-ALA69.O
LEU87.N-TYR83.O
ARG82.NH2-ALA153.O
TYR73.OH-VAL12.O
ALA68.N-LEU64.O
GLU78.OE1-ARG66.NH1
THR90.N-ALA86.O
TYR83.N-PHE79.O
TYR73.N-ALA69.O
TYR71.OH-ASP134.OD2
GLU78.OE2-ARG66.NH2
LYS91.NZ-GLY38.O
MET84.N-LEU80.O
ASP77.OD2-ARG83.NH2
TYR72.OH-VAL11.O
ARG83.NH2-SER79.OG
LYS92.NZ-HIS89.ND1
SER85.N-GLY81.O
GLU78.OE1-ARG66.NH1
TYR72.N-ALA68.O
TYR84.N-PHE80.O
TRP93.NE1-ASP108.OD1
LEU87.N-TYR83.O
GLU78.OE2-ARG66.NH2
SER78.N-ASP76.OD2
MET85.N-LEU81.O
TYR95.OH-THR90.O
THR90.N-ALA86.O
SER79.OG-ASP77.OD1
LEU80.N-ASP76.O
SER86.N-GLY82.O
VAL98.N-LEU101.O
THR90.OG1-ALA145.O
ARG83.NH2-ASP77.OD2
ARG82.NE-ALA153.O
ALA87.N-ARG83.O
THR102.OG1-ALA139.O
LYS91.NZ-ASP37.O
ARG83.NE-SER79.OG
SER85.N-GLY81.O
LEU88.N-TYR84.O
SER103.OG-GLY287.O
LYS92.NZ-ASN88.O
ARG83.NH1-ALA154.O
THR90.N-ALA86.O
THR91.N-ALA87.O
LEU118.N-ALA114.O
LYS92.NZ-HIS89.ND1
TYR84.N-PHE80.O
THR90.OG1-ALA145.O
THR91.OG1-ALA146.O
THR119.N-THR115.O
TRP93.NE1-ASP108.OD2
MET85.N-LEU81.O
LYS91.NZ-ASP37.OD1
LYS92.NZ-ASP38.O
THR119.OG1-THR115.O
GLN97.NE2-GLY100.O
SER86.OG-GLY82.O
LYS92.NZ-ASP108.OD2
LYS93.N-HIS90.O
LEU120.N-ALA116.O
GLN97.NE2-THR102.OG1
LEU88.N-TYR84.O
TRP93.NE1-ASP108.OD2
TRP94.NE1-ASP109.OD2
GLN121.NE2-LEU117.O
TYR95.OH-THR90.O
THR91.N-ALA87.O
LYS94.NZ-TRP93.O
GLN98.NE2-GLY101.O
GLN122.NE2-THR277.OG1
GLY100.N-GLN97.O
THR91.OG1-ALA146.O
TYR95.OH-THR90.O
VAL99.N-LEU102.O
ASN128.N-HIS175.O
THR102.N-GLN121.OE1
TRP94.NE1-ASP109.OD2
VAL98.N-LEU101.O
THR103.N-GLN122.OE1
GLN133.NE2-PHE127.O
THR102.OG1-ALA139.O
THR103.N-GLN122.OE1
THR102.N-GLN121.OE1
SER104.N-PRO97.O
ASP134.N-PRO130.O
SER103.N-PRO96.O
SER104.N-PRO97.O
THR102.OG1-ALA139.O
SER104.OG-GLY288.O
TYR136.OH-LEU120.O
SER103.OG-GLY287.O
SER104.OG-GLY288.O
SER103.N-PRO96.O
LYS106.N-LYS95.O
ARG138.N-ASP134.O
ASP108.OD2-TRP93.NE1
LEU119.N-SER115.O
ASN109.ND2-GLY271.O
ASN110.ND2-GLY161.O
ARG140.NH2-TYR136.OH
TYR112.OH-GLU161.O
LEU121.N-VAL117.O
TYR112.OH-GLU161.O
TYR113.OH-GLU162.O
ASN146.ND2-TYR83.OH
LEU118.N-ALA114.O
GLN122.NE2-LEU118.O
THR115.N-CYM111.O
LEU119.N-SER115.O
CYS148.N-ALA144.O
THR119.OG1-THR115.O
GLN122.NE2-THR103.O
LEU118.N-ALA114.O
LEU121.N-VAL117.O
TYR154.OH-TYR72.O
LEU120.N-ALA116.O
GLN123.NE2-THR278.OG1
GLN121.NE2-THR102.O
GLN122.NE2-THR103.O
TYR154.N-LEU150.O
GLN121.NE2-LEU117.O
LYS127.N-ASN178.OD1
GLN121.NE2-LEU117.O
GLN122.NE2-LEU118.O
LYS157.NZ-GLU161.OE1
GLN122.NE2-LEU118.O
LYS127.NZ-GLU180.OE2
ILE123.N-THR119.O
LYS127.N-ASN178.OD1
LYS157.NZ-LEU162.O
(continued)
20
1 Papain-Like Cysteine Protease (PLpro)
Table 1.5 (continued) (1) SARS-CoV-2-wt
(4) SARS-CoV-1-wt
(3) SARS-CoV-2-wt-S88
(5) SARS-CoV-1-wt-S88
(2) SARS-CoV-2-C111S-mutant
GLU124.OE2-LYS126.NZ
PHE128.N-GLN134.OE1
GLU124.OE2-LYS126.NZ
LYS127.NZ-GLU180.OE2
THR158.OG1-GLU161.OE2
LYS126.NZ-GLU124.OE2
ASN129.ND2-GLU180.OE1
LYS126.NZ-GLU124.OE2
PHE128.N-GLN134.OE1
GLU161.OE1-LYS157.NZ
PHE127.N-GLN133.OE1
ASN129.N-HIS176.O
PHE127.N-GLN133.OE1
ASN129.N-HIS176.O
ARG166.NE-GLU167.OE2
ASN128.N-HIS175.O
ALA132.N-TYR72.O
ASN128.N-HIS175.O
ASN129.ND2-GLU180.OE1
GLU167.N-ASP164.OD1
ALA131.N-TYR71.O
GLU135.N-PRO131.O
ALA131.N-TYR71.O
ALA132.N-TYR72.O
MET169.N-VAL165.O
ASP134.N-PRO130.O
GLU135.OE2-ARG139.NH1
GLN133.NE2-TYR137.OH
GLU135.N-PRO131.O
LEU172.N-THR168.O
TYR136.OH-LEU120.O
TYR137.OH-LEU121.O
ASP134.N-PRO130.O
TYR137.OH-LEU121.O
PHE173.N-MET169.O
ARG138.NE-GLU143.OE1
ARG139.NH1-GLU135.OE2
ALA135.N-ALA131.O
ARG139.NE-ASP144.OD2
GLN174.NE2-SER170.O
ARG138.NH1-ASP134.OD2
ARG139.NH2-ASN147.OD1
TYR136.OH-LEU120.O
ARG139.NH2-ASP144.OD1
ASN177.N-LYS126.O
ARG138.NH2-GLU143.OE2
ARG141.NE-TYR137.O
ARG138.NE-ASP134.OD1
ASN147.ND2-TYR84.OH
ASN177.ND2-ASN128.OD1
GLU143.OE2-ARG138.NH2
ASN147.ND2-TYR84.OH
ARG138.NH2-ASP134.OD2
CYS149.N-ALA145.O
LYS182.NZ-GLU238.OE2
ASN146.ND2-TYR83.OH
CYS149.N-ALA145.O
CYS148.N-ALA144.O
LEU153.N-CYS149.O
ARG183.N-LEU199.O
CYS148.N-ALA144.O
TYR155.N-LEU151.O
ILE151.N-PHE147.O
TYR155.N-LEU151.O
ARG183.NH1-MET206.O
ILE151.N-PHE147.O
TYR155.OH-TYR73.O
LEU152.N-CYS148.O
LYS158.N-LEU153.O
VAL184.N-GLN236.O
TYR154.OH-TYR72.O
LYS158.NZ-GLU162.OE2
TYR154.OH-TYR72.O
LYS158.NZ-GLU162.OE2
LEU185.N-THR197.O
TYR154.N-LEU150.O
LYS158.NZ-LEU163.O
TYR154.N-LEU150.O
LYS158.NZ-LEU163.O
ASN186.ND2-TYR233.OH
LYS157.NZ-GLU167.OE1
THR159.N-GLU162.OE1
CYS155.N-ILE151.O
THR159.N-GLU162.OE1
ASN186.N-TYR233.O
THR158.OG1-GLU161.OE2
VAL166.N-TYR274.OH
LYS157.NZ-GLU161.OE1
GLU162.OE2-LYS158.NZ
VAL187.N-GLN195.O
ASP164.N-GLU167.OE2
ARG167.NH2-ASP165.OD1
GLU161.OE1-LYS157.NZ
ARG167.NH2-GLU168.OE2
VAL188.N-THR231.O
THR168.N-ASP164.O
GLU168.N-ASP165.OD2
ARG166.NE-ASP302.OD1
THR169.N-ASP165.O
LYS190.NZ-LYS190.O
Table 1.6 All the HBs of the five PLpro models in http://chemcha-gpu0.ucr.edu/software/ optimized (continuation) (1) SARS-CoV-2-wt
(4) SARS-CoV-1-wt
(3) SARS-CoV-2-wt-S88
(5) SARS-CoV-1-wt-S88
(2) SARS-CoV-2-C111S-mutant
THR168.OG1-ASP164.O
THR169.OG1-ASP165.O
ARG166.NH2-ASP302.OD2
THR169.OG1-ASP165.O
LEU199.N-ARG183.O
MET169.N-VAL165.O
THR171.OG1-ARG167.O
SER170.OG-GLU167.O
THR171.OG1-ARG167.O
GLN215.NE2-GLY219.O
ASN177.N-LYS126.O
LEU173.N-THR169.O
TYR171.OH-GLU167.OE2
LYS183.NZ-GLU239.OE1
LYS217.NZ-GLU214.OE1
ASN177.ND2-ASN128.OD1
LEU174.N-MET170.O
LYS182.NZ-SER180.O
ARG184.N-LEU200.O
LYS218.NZ-GLU214.O
LYS182.N-GLU238.O
GLN175.NE2-THR171.O
ARG183.NE-GLN237.OE1
ARG184.NE-GLN238.OE1
GLY219.N-GLN215.O
LYS182.NZ-GLU238.OE2
GLU180.OE2-LYS127.NZ
ARG183.NH1-MET206.O
VAL185.N-GLN237.O
LYS200.NZ-ASP179.OD2
ARG183.NH1-MET206.O
LYS183.N-GLU239.O
VAL184.N-GLN236.O
LEU186.N-THR198.O
TYR213.OH-GLU307.OE1
VAL184.N-GLN236.O
LYS183.NZ-GLU239.OE1
LEU185.N-THR197.O
ASN187.N-TYR234.O
VAL220.N-LYS232.O
LEU185.N-THR197.O
ARG184.NE-GLN238.OE1
ASN186.N-TYR233.O
VAL188.N-LYS196.O
ILE222.N-ALA230.O
ASN186.ND2-GLN194.OE1
ARG184.NH1-MET207.O
VAL187.N-GLN195.O
VAL189.N-THR232.O
LYS228.NZ-GLY227.O
ASN186.ND2-TYR233.OH
VAL185.N-GLN237.O
VAL188.N-THR231.O
CYM190.N-GLY194.O
ALA230.N-ILE222.O
ASN186.N-TYR233.O
LEU186.N-THR198.O
GLN195.N-VAL187.O
LYS191.NZ-ASP230.OD1
THR231.OG1-GLN221.OE1
VAL188.N-THR231.O
ASN187.ND2-GLN195.OE1
THR198.OG1-GLN196.OE1
LYS196.NZ-THR198.OG1
LYS232.N-VAL220.O
THR197.N-LEU185.O
ASN187.ND2-TYR234.OH
LEU199.N-ARG183.O
LEU200.N-ARG184.O
TYR233.N-ASN186.O
LEU199.N-ARG183.O
ASN187.N-TYR234.O
MET206.N-VAL202.O
GLU204.N-GLU204.OE1
VAL235.N-VAL184.O
MET206.N-VAL202.O
VAL189.N-THR232.O
THR210.OG1-GLY209.O
MET207.N-VAL203.O
GLN237.NE2-ALA204.O
VAL205.N-VAL202.O
LYS191.NZ-ASP230.O
TYR213.OH-GLU307.OE1
TYR214.OH-GLU308.OE1
GLN237.NE2-SER239.OG
GLY209.N-SER245.O
THR198.N-LEU186.O
GLN215.NE2-GLY219.O
THR219.OG1-ASP215.O
GLU238.N-LYS182.O
TYR213.OH-GLU307.OE2
LEU200.N-ARG184.O
GLY219.N-GLN215.O
GLY220.N-ASN216.O
MET243.N-VAL205.O
GLN215.NE2-GLY219.O
MET207.N-VAL203.O
VAL220.N-LYS232.O
VAL221.N-GLN233.O
MET244.N-VAL303.O
LYS217.NZ-GLU214.OE1
GLY210.N-SER246.O
ILE222.N-ALA230.O
GLY228.N-CYM225.O
SER245.N-TYR207.O
LYS218.NZ-GLU214.O
TYR214.OH-GLU308.OE1
ALA230.N-GLY227.O
ARG229.NE-ASP230.OD2
SER245.OG-ASP302.OD1
GLY219.N-GLN215.O
THR219.OG1-ASP215.O
THR231.N-VAL188.O
ASP230.OD2-ARG229.NE
ALA246.N-THR301.O
VAL220.N-LYS232.O
GLY220.N-ASN216.O
THR231.OG1-GLN229.O
TYR234.N-ASN187.O
GLU252.OE2-LYS297.NZ
GLN221.NE2-THR231.OG1
VAL221.N-GLN233.O
LYS232.N-VAL220.O
TYR234.OH-ILE315.OXT
LEU253.N-TYR296.O
ILE222.N-ALA230.O
ARG229.NH1-GLY228.O
TYR233.N-ASN186.O
VAL236.N-VAL185.O
LYS254.NZ-GLU252.OE1
LYS228.N-CYM226.O
GLN233.NE2-TYR208.OH
LEU234.N-PHE216.O
GLN238.NE2-ALA205.O
LYS254.NZ-GLU295.OE2
THR231.N-VAL188.O
GLN233.N-VAL221.O
VAL235.N-VAL184.O
GLN238.NE2-SER240.OG
HIS255.NE2-LYS279.O
LYS232.NZ-TYR207.OH
TYR234.N-ASN187.O
GLN236.NE2-THR311.OG1
SER241.OG-GLU125.O
THR259.N-PHE304.O
LYS232.N-VAL220.O
TYR234.OH-ILE315.OXT
GLN237.NE2-ALA204.O
VAL243.N-TYR306.O
ALA261.N-ILE276.O
TYR233.N-ASN186.O
VAL236.N-VAL185.O
GLN237.NE2-SER239.OG
MET244.N-VAL206.O
SER262.OG-THR115.OG1
LEU234.N-PHE216.O
GLN238.NE2-ALA205.O
GLU238.N-LYS182.O
MET245.N-VAL304.O
GLU263.N-LYS274.O
VAL235.N-VAL184.O
GLN238.N-TYR311.O
SER239.OG-PHE241.O
SER246.N-TYR208.O
TYR264.OH-ASN267.O
GLN237.NE2-ALA204.O
GLU239.OE1-LYS183.NZ
VAL242.N-TYR305.O
SER246.OG-ASP303.OD1
TYR264.N-PRO299.O
(continued)
Supplementary Information
21
Table 1.6 (continued) (1) SARS-CoV-2-wt
(4) SARS-CoV-1-wt
(3) SARS-CoV-2-wt-S88
(5) SARS-CoV-1-wt-S88
(2) SARS-CoV-2-C111S-mutant
GLN237.N-TYR310.O
SER240.OG-PHE242.O
MET244.N-VAL303.O
ALA247.N-THR302.O
ASN267.N-CYS270.O
GLU238.N-LYS182.O
VAL243.N-TYR306.O
SER245.N-TYR207.O
TYR252.N-GLY299.O
HIS272.NE2-ASP286.OD1
GLU238.OE2-LYS182.NZ
SER246.N-TYR208.O
SER245.OG-ASP302.OD1
LEU254.N-TYR297.O
LYS274.N-GLU263.O
SER239.OG-PHE241.O
SER246.OG-ASP303.OD1
ALA246.N-THR301.O
GLN256.NE2-SER295.O
LYS274.NZ-GLU263.OE1
VAL242.N-TYR305.O
ALA247.N-THR302.O
GLU252.OE1-LYS254.NZ
THR258.OG1-GLN255.O
HIS275.NE2-GLN122.OE1
MET243.N-VAL205.O
GLU251.OE2-LYS298.NZ
LEU253.N-TYR296.O
ALA262.N-ILE277.O
ILE276.N-ALA261.O
MET244.N-VAL303.O
LYS253.NZ-GLN255.OE1
LYS254.NZ-GLU252.OE1
ASN263.N-ASP303.O
THR277.OG1-THR259.O
SER245.N-TYR207.O
LEU254.N-TYR297.O
LYS254.NZ-GLU295.OE1
ASN263.ND2-ASP303.OD2
LYS279.NZ-GLU280.OE1
SER245.OG-ASP302.OD1
GLN256.NE2-SER295.O
GLY256.N-SER278.OG
TYR265.OH-ASN268.O
LYS279.N-THR281.O
ALA246.N-THR301.O
LEU260.N-PHE305.O
THR257.OG1-LYS254.O
THR266.N-HIS273.O
GLU280.N-GLU280.OE1
LEU253.N-TYR296.O
ASN263.N-ASP303.O
SER262.OG-ASP302.OD2
ASN268.N-CYS271.O
TYR283.N-THR277.O
HIS255.N-SER294.O
ASN263.ND2-ASP303.OD2
TYR264.OH-ASN267.O
HIS273.NE2-ASP287.OD1
TYR283.OH-GLU280.OE2
SER262.OG-ASP302.OD2
GLU264.N-THR275.O
TYR264.N-PRO299.O
HIS276.NE2-GLN123.OE1
ILE285.N-HIS275.O
TYR264.N-PRO299.O
TYR265.N-PRO300.O
ASN267.N-CYS270.O
ILE277.N-ALA262.O
ASP286.OD1-HIS272.NE2
TYR264.OH-TYR268.O
THR266.N-HIS273.O
HIS272.N-THR265.O
LYS280.NZ-GLU281.OE2
ASP286.N-LEU289.O
HIS272.NE2-ASP286.OD1
TYR269.OH-ASP165.OD1
HIS272.NE2-ASP286.OD2
LEU283.N-MET294.O
THR291.N-CYS284.O
LYS274.N-GLU263.O
HIS273.NE2-ASP287.OD1
HIS275.NE2-GLN122.OE1
TYR284.N-THR278.O
SER293.N-LEU282.O
LYS274.NZ-GLU263.OE1
HIS273.N-THR266.O
ILE276.N-ALA261.O
TYR284.OH-GLU281.OE1
SER293.OG-GLU295.O
HIS275.N-ILE285.O
THR275.OG1-TYR274.O
TYR283.N-THR277.O
ARG285.NE-GLU264.OE1
TYR296.OH-GLU263.OE2
THR277.OG1-GLN122.OE1
ILE277.N-ALA262.O
TYR283.OH-GLU280.OE2
ARG285.NH2-GLU264.OE2
LYS297.NZ-GLU252.OE2
THR277.N-TYR283.O
THR278.OG1-LEU260.O
CYS284.N-THR291.O
ARG285.NH1-ASP287.OD2
THR301.N-SER262.O
LYS279.NZ-GLU280.OE1
THR278.N-TYR284.O
ILE285.N-HIS275.O
ARG285.N-THR292.O
THR301.OG1-ASP302.OD2
GLU280.OE1-LYS279.NZ
MET244.N-VAL206.O
ASP286.OD2-HIS272.NE2
ILE286.N-HIS276.O
PHE304.N-CYS260.O
TYR283.N-THR277.O
MET245.N-VAL304.O
ASP286.N-LEU289.O
ASP287.OD1-HIS273.NE2
TYR305.N-VAL242.O
TYR283.OH-GLU280.OE2
LYS280.N-THR282.O
SER294.OG-GLU295.OE2
ASP287.N-HIS290.O
LYS306.NZ-GLU307.O
CYS284.N-THR291.O
LYS280.NZ-GLY100.O
TYR296.N-LEU253.O
THR292.N-ARG285.O
LYS306.NZ-ASN308.OD1
ILE285.N-HIS275.O
GLU281.OE2-LYS293.NZ
TYR296.OH-GLU263.OE1
SER295.OG-GLU296.OE2
ASN308.N-GLU307.OE2
ASP286.OD1-HIS272.NE2
TYR284.N-THR278.O
THR301.N-SER262.O
TYR297.N-LEU254.O
SER309.OG-GLU238.OE1
ASP286.N-LEU289.O
TYR284.OH-GLU281.OE1
THR301.OG1-ALA246.O
TYR297.OH-GLU264.OE1
LEU289.N-ASP286.O
ARG285.NE-GLU264.OE1
PHE304.N-CYS260.O
LYS298.NZ-GLU251.OE1
SER293.OG-GLU295.O
ARG285.NH1-ASP287.OD2
TYR305.OH-LEU211.O
THR302.N-ASN263.O
SER294.OG-GLU295.OE1
ARG285.NH2-GLU264.OE2
TYR305.N-VAL242.O
THR302.OG1-ALA247.O
TYR296.OH-GLU263.OE2
ARG285.N-THR292.O
GLU307.OE1-TYR213.OH
VAL304.N-MET245.O
LYS297.NZ-GLU252.OE2
ILE286.N-HIS276.O
ASN308.N-GLU307.OE2
PHE305.N-CYS261.O
THR301.OG1-ALA246.O
ASP287.OD1-HIS273.NE2
TYR310.N-GLN237.O
TYR306.OH-LEU212.O
VAL303.N-MET244.O
THR292.N-ARG285.O
TYR306.N-VAL243.O
PHE304.N-CYS260.O
LYS293.NZ-GLU281.OE2
THR309.N-GLU308.OE2
TYR305.N-VAL242.O
TYR297.OH-GLU264.OE1
SER310.OG-GLU239.OE2
ASN308.N-GLU307.OE1
LYS298.NZ-GLU251.OE2
TYR311.N-GLN238.O
SER309.OG-GLU238.OE1
THR302.N-ASN263.O
TYR310.N-GLN237.O
THR302.OG1-ALA247.O
THR312.N-VAL235.O
VAL304.N-MET245.O PHE305.N-CYS261.O TYR306.OH-LEU212.O TYR306.N-VAL243.O LYS307.NZ-GLU308.O GLU308.N-SER241.O THR309.N-GLU308.OE2 TYR311.N-GLN238.O THR314.OG1-THR313.O
22
1 Papain-Like Cysteine Protease (PLpro)
Table 1.7 All the HBs (with more than 30% occupancy rates) of the SARS-CoV-2-wt and SARSCoV-1-wt models with/without ligand S88 bound in http://chemcha-gpu0.ucr.edu/software/ during 1 μs’ MDs (1) SARS-CoV-2-wt
(4) SARS-CoV-1-wt
(3) SARS-CoV-2-wt-S88
(5) SARS-CoV-1-wt-S88
THR168.OG1-ASP164.O 68.43%
SER246.OG-ASP303.OD1 73.35%
SER245.OG-ASP302.OD1 79.12%
SER246.OG-ASP303.OD1 78.62%
TYR72.OH-VAL11.O 65.13%
TYR73.OH-VAL12.O 73.15%
TYR264.OH-ASN267.O 75.22%
THR302.OG1-ALA247.O 74.43%
LYS105.N-LYS94.O 63.14%
THR302.N-ASN263.O 68.46%
THR301.OG1-ALA246.O 73.83%
THR302.N-ASN263.O 73.03%
TYR95.OH-THR90.O 63.04%
THR169.OG1-ASP165.O 63.67%
LYS105.N-LYS94.O 63.44%
TYR265.OH-ASN268.O 73.03%
GLN237.NE2-ALA204.O 61.94%
LYS106.N-LYS95.O 61.28%
GLN237.NE2-ALA204.O 62.04%
TYR73.OH-VAL12.O 69.63%
SER245.OG-ASP302.OD1 61.94%
THR302.OG1-ALA247.O 60.18%
THR301.N-SER262.O 61.94%
THR169.OG1-ASP165.O 68.53%
SER239.OG-PHE241.O 58.14%
THR171.OG1-ARG167.O 59.78%
THR168.OG1-ASP164.O 61.64%
ILE286.N-HIE276.O 62.64%
ASN128.N-HIE175.O 57.24%
TYR155.N-LEU151.O 59.58%
TYR305.OH-LEU211.O 60.04%
SER116.OG-ASN263.OD1 62.64%
TYR305.OH-LEU211.O 56.44%
TYR155.OH-TYR73.O 59.08%
TYR95.OH-THR90.O 59.24%
THR171.OG1-ARG167.O 61.64%
THR115.OG1-CYM111.O 56.34%
LEU200.N-ARG184.O 58.78%
TYR72.OH-VAL11.O 58.04%
ASN263.ND2-ASP303.OD2 60.84%
THR90.N-ALA86.O 54.75%
TYR306.OH-LEU212.O 58.68%
ASN128.N-HIE175.O 56.24%
SER156.OG-ILE152.O 59.54%
LEU199.N-ARG183.O 53.75%
THR219.OG1-ASP215.O 56.99%
THR34.OG1-GLY32.O 55.64%
TYR306.OH-LEU212.O 58.94%
MET244.N-VAL303.O 53.55%
ASN263.ND2-ASP303.OD2 56.99%
SER239.OG-PHE241.O 53.95%
GLN238.NE2-ALA205.O 58.34%
TYR154.N-LEU150.O 52.55%
ILE286.N-HIE276.O 55.59%
LEU199.N-ARG183.O 53.85%
TYR155.N-LEU151.O 56.44%
VAL98.N-LEU101.O 52.55%
GLN238.NE2-ALA205.O 55.19%
PHE173.N-MET169.O 53.75%
TYR155.OH-TYR73.O 55.84%
ILE285.N-HIE275.O 52.25%
SER156.OG-ILE152.O 55.19%
THR115.OG1-CYM111.O 53.65%
LYS106.N-LYS95.O 55.44%
PHE55.N-PHE8.O 51.65%
THR35.OG1-GLY33.O 55.09%
ILE285.N-HIE275.O 53.25%
THR35.OG1-GLY33.O 54.85%
GLN121.NE2-LEU117.O 51.35%
MET244.N-VAL206.O 52.89%
VAL98.N-LEU101.O 50.85%
LEU200.N-ARG184.O 53.55%
TYR213.OH-GLU307.OE2 50.25%
PHE56.N-PHE9.O 52.40%
SER103.OG-GLY287.O 50.25%
MET244.N-VAL206.O 51.55%
LEU253.N-TYR296.O 50.15%
SER116.OG-ASN263.OD1 51.80%
THR90.N-ALA86.O 50.15%
THR219.OG1-ASP215.O 51.25%
MET169.N-VAL165.O 50.05%
VAL189.N-THR232.O 51.10%
MET244.N-VAL303.O 49.75%
PHE56.N-PHE9.O 50.15%
PHE304.N-CYS260.O 49.95%
PHE305.N-CYS261.O 49.70%
LEU253.N-TYR296.O 49.55%
GLN122.NE2-LEU118.O 49.85%
SER103.OG-GLY287.O 48.15%
VAL99.N-LEU102.O 49.20%
VAL7.N-GLN19.O 48.75%
VAL8.N-GLN20.O 49.65%
TYR27.OH-HIE50.ND1 47.65%
LEU186.N-THR198.O 48.80%
THR10.OG1-ASN15.O 48.55%
GLN233.N-VAL221.O 49.65%
THR119.OG1-THR115.O 47.55%
GLN233.N-VAL221.O 47.80%
TYR154.N-LEU150.O 48.35%
PHE305.N-CYS261.O 49.25%
THR301.OG1-ALA246.O 46.35%
MET245.N-VAL304.O 47.70%
GLY209.N-SER245.O 48.25%
LEU37.N-ALA40.O 48.85%
LEU120.N-ALA116.O 45.95%
GLY210.N-SER246.O 47.31%
PHE55.N-PHE8.O 48.05%
MET245.N-VAL304.O 48.35%
PHE31.N-TYR27.O 45.75%
GLY53.N-LYS7.O 46.81%
ASP22.N-GLN30.OE1 48.05%
SER104.OG-GLY288.O 47.75%
CYS284.N-THR291.O 45.55%
VAL8.N-GLN20.O 46.81%
GLN121.NE2-LEU117.O 47.65%
VAL99.N-LEU102.O 47.55%
LEU185.N-THR197.O 45.05%
SER79.OG-ASP77.OD2 45.81%
PHE304.N-CYS260.O 47.35%
GLY53.N-LYS7.O 46.85%
LEU117.N-LEU113.O 44.46%
LEU37.N-ALA40.O 45.61%
THR257.OG1-LYS254.O 46.65%
LEU174.N-MET170.O 46.45%
PHE173.N-MET169.O 44.16%
GLN122.NE2-LEU118.O 44.71%
CYS284.N-THR291.O 46.25%
GLU264.N-THR275.O 46.25%
TYR154.OH-TYR72.O 43.86%
LEU254.N-TYR297.O 43.61%
LEU185.N-THR197.O 45.85%
TYR297.OH-GLU264.OE1 45.85%
THR301.N-SER262.O 43.86%
ASN111.N-ALA108.O 43.61%
PHE31.N-TYR27.O 45.75%
VAL189.N-THR232.O 45.55%
THR10.OG1-ASN15.O 43.66%
PHE128.N-GLN134.OE1 43.61%
TYR305.N-VAL242.O 45.55%
TYR73.N-ALA69.O 45.45%
LEU36.N-ALA39.O 42.46%
TYR297.OH-GLU264.OE1 43.51%
ASN186.N-TYR233.O 45.45%
GLN20.N-VAL8.O 45.15%
TYR83.N-PHE79.O 42.06%
TYR284.N-THR278.O 43.41%
LEU118.N-ALA114.O 45.15%
LEU186.N-THR198.O 44.76%
GLY52.N-LYS6.O 41.56%
LEU174.N-MET170.O 43.31%
LEU36.N-ALA39.O 44.66%
TYR36.N-PHE57.O 44.66%
GLY219.N-GLN215.O 41.46%
TYR306.N-VAL243.O 43.31%
LEU117.N-LEU113.O 43.66%
MET170.N-VAL166.O 44.06%
ASP286.N-LEU289.O 41.16%
LEU119.N-SER115.O 43.11%
LEU120.N-ALA116.O 43.46%
TYR306.N-VAL243.O 43.86%
VAL7.N-GLN19.O 41.06%
PHE32.N-TYR28.O 43.01%
MET169.N-VAL165.O 41.86%
PHE32.N-TYR28.O 43.76%
TYR83.OH-ASN146.OD1 40.96%
THR11.OG1-ASN16.O 42.81%
ASP286.N-LEU289.O 40.46%
VAL304.N-MET245.O 43.56%
THR277.N-TYR283.O 40.76%
TYR234.N-ASN187.O 42.61%
GLN19.N-VAL7.O 39.96%
LEU119.N-SER115.O 43.36%
GLN121.NE2-THR102.O 40.76%
GLN122.NE2-THR103.O 42.51%
CYS148.N-ALA144.O 39.46%
TYR208.OH-GLN233.OE1 43.26%
TYR72.N-ALA68.O 40.66%
MET170.N-VAL166.O 42.51%
GLY219.N-GLN215.O 39.46%
ASP23.N-GLN31.OE1 43.26%
GLY209.N-SER245.O 40.66%
SER240.OG-PHE242.O 41.92%
THR102.N-GLN121.OE1 39.36%
THR11.OG1-ASN16.O 42.76%
VAL303.N-MET244.O 40.56%
TYR73.N-ALA69.O 41.12%
MET243.N-VAL205.O 39.06%
ARG285.N-THR292.O 42.76%
LEU87.N-TYR83.O 40.46%
VAL304.N-MET245.O 40.92%
PHE127.N-GLN133.OE1 38.96%
THR103.OG1-ALA140.O 42.76%
LEU118.N-ALA114.O 40.46%
ARG66.N-ASP62.O 40.82%
TYR27.OH-HIE50.ND1 38.96%
VAL221.N-GLN233.O 42.56%
Supplementary Information
23
Table 1.8 All the HBs (with more than 30% occupancy rates) of the SARS-CoV-2-wt and SARS-CoV-1-wt models with/without ligand S88 bound in http://chemcha-gpu0.ucr.edu/ software/ during 1 μs’ MDs (continuation) (1) SARS-CoV-2-wt
(4) SARS-CoV-1-wt
(3) SARS-CoV-2-wt-S88
(5) SARS-CoV-1-wt-S88
ARG183.NE-GLN237.OE1 40.26%
TYR84.N-PHE80.O 40.72%
VAL21.N-ILE5.O 38.56%
LEU254.N-TYR297.O 42.06%
THR102.N-GLN121.OE1 40.26%
TYR28.OH-HIE51.ND1 40.52%
VAL303.N-MET244.O 38.26%
LEU118.N-LEU114.O 41.56%
ILE151.N-PHE147.O 40.16%
GLU264.N-THR275.O 40.02%
GLN121.NE2-THR102.O 38.16%
ASN111.N-ALA108.O 40.76%
TYR305.N-VAL242.O 39.46%
TYR36.N-PHE57.O 39.72%
ASN110.N-ALA107.O 38.16%
THR275.OG1-TYR274.O 40.76%
CYS148.N-ALA144.O 39.26%
TYR214.OH-GLU308.OE1 39.32%
MET84.N-LEU80.O 37.76%
TYR84.N-PHE80.O 40.56%
TYR296.OH-GLU263.OE2 38.96%
ARG285.N-THR292.O 39.02%
SER103.N-PRO96.O 37.56%
GLY210.N-SER246.O 40.26%
ASN110.N-ALA107.O 38.16%
LEU121.N-VAL117.O 38.72%
ASN15.N-ASP12.OD2 37.46%
GLN122.NE2-THR103.O 40.26%
ASN186.N-TYR233.O 37.86%
SER25.OG-ASP23.OD1 38.02%
LEU87.N-TYR83.O 37.46%
SER240.OG-PHE242.O 40.06%
SER103.N-PRO96.O 37.26%
MET85.N-LEU81.O 37.92%
ALA131.N-TYR71.O 37.26%
TYR234.N-ASN187.O 39.86%
PHE8.N-LYS53.O 37.06%
THR258.OG1-GLN255.O 37.62%
GLY52.N-LYS6.O 36.96%
ASN187.N-TYR234.O 38.96%
PHE127.N-GLN133.OE1 37.06%
SER25.OG-ASP23.OD2 37.52%
SER262.OG-ASP302.OD2 36.86%
SER104.N-PRO97.O 38.16%
SER85.OG-GLY81.O 36.86%
LEU118.N-LEU114.O 37.43%
TRP93.NE1-ASP108.OD1 36.56%
THR91.N-ALA87.O 38.16%
ASN15.N-ASP12.OD2 36.16%
ASN129.N-HIE176.O 37.13%
TYR296.OH-GLU263.OE2 36.06%
TYR28.OH-HIE51.ND1 37.76%
VAL184.N-GLN236.O 36.06%
GLN20.N-VAL8.O 36.83%
MET206.N-VAL202.O 35.46%
MET85.N-LEU81.O 37.26%
TYR310.N-GLN237.O 35.66%
SER104.OG-GLY288.O 36.73%
TYR56.N-TYR35.O 35.46%
LEU88.N-TYR84.O 36.76%
TYR56.N-TYR35.O 35.36%
LEU88.N-TYR84.O 36.53%
ALA246.N-THR301.O 35.26%
THR258.OG1-GLN255.O 36.66%
THR42.OG1-ASP40.OD2 35.36%
TYR265.OH-ASN268.O 36.23%
SER24.OG-ASP22.OD1 35.16%
VAL22.N-ILE6.O 36.46%
LEU234.N-PHE216.O 34.87%
VAL221.N-GLN233.O 36.03%
THR34.N-THR42.OG1 34.97%
ARG66.N-ASP62.O 36.36%
MET84.N-LEU80.O 34.77%
ASN178.N-LYS127.O 35.93%
GLN237.N-TYR310.O 34.97%
TYR284.N-THR278.O 35.96%
THR257.OG1-LYS254.O 34.67%
PHE57.N-TYR36.O 35.83%
ILE151.N-PHE147.O 34.77%
ASN178.N-LYS127.O 34.77%
SER78.OG-ASP76.OD1 34.27%
TYR208.OH-GLN233.OE1 35.23%
TYR35.N-TYR56.O 34.57%
ASN129.N-HIE176.O 34.67%
THR9.N-HIE17.O 34.17%
TYR297.N-LEU254.O 35.13%
TYR83.N-PHE79.O 34.17%
THR103.N-GLN122.OE1 34.67%
VAL220.N-LYS232.O 33.57%
THR198.N-LEU186.O 34.23%
ASP134.N-PRO130.O 34.17%
PHE128.N-GLN134.OE1 34.57%
SER24.OG-ASP22.OD2 33.47%
VAL22.N-ILE6.O 34.03%
TYR83.OH-ASN146.OD1 34.07%
THR266.N-HIP273.O 34.27%
ALA246.N-THR301.O 33.37%
SER104.N-PRO97.O 33.73%
THR277.N-TYR283.O 33.87%
ALA247.N-THR302.O 34.27%
TYR296.OH-GLU263.OE1 33.17%
ASN187.N-TYR234.O 33.63%
TYR72.N-ALA68.O 33.57%
ASN263.N-ASP303.O 34.17%
VAL188.N-THR231.O 33.07%
ALA247.N-THR302.O 33.53%
SER262.N-ASP302.O 33.57%
TYR214.OH-GLU308.OE1 33.97%
ALA131.N-TYR71.O 32.67%
THR103.OG1-ALA140.O 33.53%
SER24.OG-ASP22.OD2 33.27%
PHE57.N-TYR36.O 33.97%
MET206.N-VAL202.O 32.67%
SER67.OG-ASP63.O 33.53%
LEU234.N-PHE216.O 32.87%
SER25.OG-ASP23.OD1 33.57%
SER24.OG-ASP22.OD1 32.27%
ASP23.N-GLN31.OE1 33.33%
VAL220.N-LYS232.O 32.87%
TYR137.OH-LEU121.O 33.47%
THR42.OG1-ASP40.OD1 32.27%
TYR297.OH-GLU264.OE2 33.03%
THR42.OG1-ASP40.OD2 32.77%
TYR297.N-LEU254.O 33.07%
VAL21.N-ILE5.O 32.17%
MET207.N-VAL203.O 32.34%
ASN15.ND2-ASP12.OD1 31.67%
THR198.N-LEU186.O 32.97%
ASN308.N-GLU307.OE1 31.57%
THR43.OG1-ASP41.OD2 32.24%
TYR136.OH-LEU120.O 31.47%
THR91.OG1-ALA146.O 32.77%
ASN15.ND2-ASP12.OD1 31.57%
THR43.OG1-ASP41.OD1 32.24%
VAL242.N-TYR305.O 31.37%
ALA140.N-ALA136.O 32.67%
TYR35.N-TYR56.O 31.07%
ILE6.N-VAL22.O 32.24%
VAL184.N-GLN236.O 31.17%
SER86.N-GLY82.O 32.47%
SER170.OG-ARG166.O 31.07%
VAL58.N-THR11.O 32.14%
ARG183.NE-GLN237.OE1 30.97%
CYS149.N-ALA145.O 32.37%
SER262.N-ASP302.O 30.67%
VAL185.N-GLN237.O 31.84%
VAL187.N-GLN195.O 30.47%
SER79.OG-ASP77.OD2 32.17%
SER85.N-GLY81.O 30.47%
THR91.N-ALA87.O 31.64%
THR42.OG1-ASP40.OD1 30.47%
THR43.OG1-ASP41.OD1 32.07%
THR115.N-CYM111.O 30.17%
TYR137.OH-LEU121.O 31.54%
VAL57.N-THR10.O 30.27%
PHE70.N-ARG66.O 31.87%
GLN237.N-TYR310.O 30.07%
LEU151.N-ASN147.O 31.54%
PHE8.N-LYS53.O 29.57%
TYR252.N-GLY299.O 31.77%
TYR213.OH-GLU307.OE1 29.97%
ASP287.N-HIE290.O 31.34%
SER49.OG-HIE47.ND1 29.47%
ILE223.N-ALA231.O 31.77%
ASP134.N-PRO130.O 29.87%
THR275.OG1-TYR274.O 30.84%
ALA114.N-ASN110.O 29.47%
SER25.OG-ASP23.OD2 31.57%
ALA114.N-ASN110.O 29.57%
ASN16.N-ASP13.OD2 30.84%
LYS232.N-VAL220.O 29.27%
ALA262.N-ILE277.O 30.87%
THR90.OG1-ALA145.O 29.07%
TYR252.N-GLY299.O 30.54%
VAL41.N-THR34.O 28.97%
TYR297.OH-GLU264.OE2 30.77%
THR102.OG1-ALA139.O 28.87%
ASN263.N-ASP303.O 30.34%
LYS182.N-GLU238.O 28.67%
HIP273.N-THR266.O 30.67%
VAL57.N-THR10.O 28.57%
PHE9.N-LYS54.O 30.34%
THR102.OG1-ALA139.O 28.57%
PHE9.N-LYS54.O 30.47%
TYR136.OH-LEU120.O 28.17%
ASN16.ND2-ASP13.OD1 29.94%
SER85.OG-GLY81.O 28.57%
ALA120.N-SER116.O 30.47%
ASN177.N-LYS126.O 28.07%
PHE70.N-ARG66.O 29.74%
PHE69.N-ARG65.O 28.57%
THR43.OG1-ASP41.OD2 30.37%
LYS157.N-LEU152.O 27.97%
MET24.N-LYS4.O 29.74%
THR115.N-CYM111.O 28.57%
SER67.OG-ASP63.O 30.27%
VAL187.N-GLN195.O 27.87%
GLU239.N-LYS183.O 29.54%
TYR296.OH-GLU263.OE1 28.47%
LYS183.N-GLU239.O 30.07%
24
1 Papain-Like Cysteine Protease (PLpro)
Fig. 1.11 The Secondary Structure performances of the five PLpro models: (1) SARS-CoV-2-wt, (4) SARS-CoV-1-wt, (3) SARS-CoV-2-wt-S88, (5) SARS-CoV-1-wt-S88, and (2) SARS-CoV-2C111S-mutant during 1 μs’ MDs of http://chemcha-gpu0.ucr.edu/software/
Table 1.9 All the HBs (with more than 30% occupancy rates) of the SARS-CoV-2-C111S-mutant model in http://chemchagpu0.ucr.edu/software/ during the 1 μs’ MD
(2) SARS-CoV-2-C111S-mutant SER245.OG-ASP302.OD1 72.93%
GLU238.N-LYS182.O 34.87%
TYR72.OH-VAL11.O 65.83%
SER24.OG-ASP22.OD1 34.87%
THR168.OG1-ASP164.O 63.74%
GLN121.NE2-THR102.O 34.67%
LYS105.N-LYS94.O 62.04%
SER78.OG-ASP76.OD2 33.97%
TYR95.OH-THR90.O 61.34%
GLN237.N-TYR310.O 33.47%
ASN128.N-HIE175.O 59.54%
PHE8.N-LYS53.O 33.17%
TYR154.OH-TYR72.O 57.94%
TYR233.N-ASN186.O 32.97%
THR34.OG1-GLY32.O 57.04%
ILE222.N-ALA230.O 32.97%
ILE285.N-HIE275.O 56.04%
THR9.N-HIE17.O 32.77%
TYR154.N-LEU150.O 55.84%
THR90.OG1-ALA145.O 32.47%
PHE304.N-CYS260.O 55.24%
THR42.OG1-ASP40.OD1 31.67%
GLN237.NE2-ALA204.O 54.75%
PHE127.N-GLN133.OE1 31.67%
VAL98.N-LEU101.O 54.25%
THR102.N-GLN121.OE1 31.37%
MET84.N-LEU80.O 53.95%
SER24.OG-ASP22.OD2 30.97%
LEU199.N-ARG183.O 53.65%
LEU150.N-ASN146.O 30.77%
THR119.OG1-THR115.O 53.45%
LYS157.N-LEU152.O 30.77%
THR301.N-SER262.O 51.65%
TYR296.OH-GLU263.OE1 30.57%
VAL7.N-GLN19.O 49.85%
TYR56.N-TYR35.O 30.47%
GLN121.NE2-LEU117.O 49.15%
MET206.N-VAL202.O 30.37%
LEU253.N-TYR296.O 48.55%
ASN186.N-TYR233.O 30.27%
PHE31.N-TYR27.O 48.15%
VAL184.N-GLN236.O 29.67%
TYR305.OH-LEU211.O 47.95%
LEU234.N-PHE216.O 29.37%
SER103.OG-GLY287.O 47.95%
TRP93.NE1-ASP108.OD2 29.17%
LYS232.N-VAL220.O 47.65%
VAL242.N-TYR305.O 29.17%
PHE55.N-PHE8.O 47.25%
THR34.N-THR42.OG1 28.97%
LEU185.N-THR197.O 47.05%
THR42.OG1-ASP40.OD2 28.97%
SER239.OG-PHE241.O 46.65%
LYS182.N-GLU238.O 28.77%
LEU120.N-ALA116.O 46.45%
THR301.OG1-ALA246.O 28.77%
MET169.N-VAL165.O 46.35%
SER85.N-GLY81.O 28.67%
PHE173.N-MET169.O 46.25%
HIP272.N-THR265.O 28.27%
THR10.OG1-ASN15.O 46.15%
TYR264.OH-ASN267.O 28.17%
LEU117.N-LEU113.O 46.05%
TYR296.OH-GLU263.OE2 27.97%
THR277.N-TYR283.O 45.95%
ASN15.ND2-ASP12.OD2 27.87%
GLY52.N-LYS6.O 45.75%
THR259.N-PHE304.O 27.77%
MET243.N-VAL205.O 45.65%
VAL41.N-THR34.O 27.37%
LEU36.N-ALA39.O 45.05%
ARG82.NE-SER78.OG 26.57%
TYR83.N-PHE79.O 44.46%
THR277.OG1-GLN122.OE1 26.57%
ASP286.N-LEU289.O 43.86%
VAL57.N-THR10.O 26.37%
THR90.N-ALA86.O 43.86%
GLU263.N-LYS274.O 26.27%
MET244.N-VAL303.O 43.76%
SER49.OG-HIE47.ND1 26.27%
LEU87.N-TYR83.O 43.56%
ILE276.N-ALA261.O 26.17%
THR115.OG1-CYM111.O 43.06%
TYR83.OH-ASN146.OD1 26.17%
CYS284.N-THR291.O 42.96%
CYM189.N-GLY193.O 26.07%
GLY209.N-SER245.O 42.96%
TRP93.NE1-ASP108.OD1 26.07%
TYR72.N-ALA68.O 42.76%
ASN308.N-GLU307.OE1 25.87%
TYR35.N-TYR56.O 42.56%
THR257.OG1-LYS254.O 25.57%
VAL303.N-MET244.O 41.86%
ASP134.N-PRO130.O 24.98%
LEU118.N-ALA114.O 41.26%
LYS274.N-GLU263.O 24.78%
TYR283.N-THR277.O 41.06%
THR63.OG1-ASP61.OD1 24.78%
THR301.OG1-ASP302.OD2 41.06%
THR115.N-CYM111.O 24.78%
TYR213.OH-GLU307.OE1 40.76%
ARG140.N-TYR136.O 24.58%
VAL220.N-LYS232.O 40.76%
THR63.OG1-ASP61.OD2 24.48%
ASN110.N-ALA107.O 40.46%
TYR264.N-PRO299.O 24.48%
TYR27.OH-HIE50.ND1 40.36%
ARG65.N-ASP61.O 24.48%
TYR305.N-VAL242.O 39.76%
VAL188.N-THR231.O 24.28%
ASN177.N-LYS126.O 39.36%
ILE123.N-THR119.O 23.98%
THR102.OG1-ALA139.O 39.06%
ASN308.N-GLU307.OE2 23.78%
TYR213.OH-GLU307.OE2 38.76%
SER170.OG-ARG166.O 23.68%
VAL21.N-ILE5.O 38.26%
ARG82.N-SER78.O 23.58%
CYS148.N-ALA144.O 37.96%
TYR136.OH-LEU120.O 23.08%
ALA246.N-THR301.O 37.76%
GLN196.NE2-ASN186.OD1 22.88%
GLN19.N-VAL7.O 37.66%
ALA139.N-ALA135.O 22.78%
ASN15.N-ASP12.OD1 37.06%
GLU70.N-VAL66.O 22.78%
SER85.OG-GLY81.O 36.76%
ALA114.N-ASN110.O 22.78%
SER262.N-ASP302.O 36.16%
THR197.N-LEU185.O 22.58%
SER78.OG-ASP76.OD1 36.06%
VAL187.N-GLN195.O 22.28%
TYR310.N-GLN237.O 36.06%
HIE17.N-THR9.O 21.98%
SER103.N-PRO96.O 36.06%
CYS155.N-ILE151.O 21.98%
ILE151.N-PHE147.O 35.76%
TYR251.N-GLY298.O 20.68%
ASP22.N-GLN30.OE1 35.56%
ASN110.ND2-LYS105.O 20.58%
GLY219.N-GLN215.O 35.56%
HIE50.N-HIE47.O 20.48% ASN88.N-MET84.O 20.38%
26
1 Papain-Like Cysteine Protease (PLpro)
Table 1.10 All the π -interactions and ZN316 binding residues of the five PLpro models in http:// chemcha-gpu0.ucr.edu/software/ optimized (1) SARS-CoV-2-wt
(4) SARS-CoV-1-wt
(3) SARS-CoV-2-wt-S88
π -π stackings
(5) SARS-CoV-1-wt-S88
(2) SARS-CoV-2-C111S-mutant
HIS48-HIS51 HIS50-PHE55
HIS51-PHE56
HIS51-PHE56
TYR71-TYR72
TYR72-TYR73
TYR72-TYR73
TYR71-TYR72
PHE80-TYR155 TYR93-HIS89-TYR93 TRP107-HIS273-TRP107
TRP106-HIS272-TRP106
TRP106-HIS272-TRP106
PHE128-TYR137 PHE173-PHE241
PHE173-PHE241 TYR207-PHE216
TYR207-PHE216 TYR265-TYR274
π -cations
LYS217.NZ+-TYR310
HIS272.ND1+-TRP106
HIS273.ND1+-TRP107
HIS272.ND1+-TRP106
LYS217.NZ+-TYR310
LYS218.NZ+-TYR311
CYM189
CYM190
CYM189
CYM190
LYS279.NZ+-TYR283
ZN316
LYS218.NZ+-TYR311
HIS272.ND1+ = TRP106 CYM189 THR191 CYS192
PRO224 CYS224
CYM225
CYM226
CYS224
CYM225
CYM226
CYS227
CYM226
LYS228 GLN229 ALA230
GLY228 ALA231
ALA230
Fig. 1.12 The Secondary Structures of the five PLpro models: (1) SARS-CoV-2-wt, (4) SARSCoV-1-wt, (3) SARS-CoV-2-wt-S88, (5) SARS-CoV-1-wt-S88, and (2) SARS-CoV-2-C111Smutant of http://chemcha-gpu0.ucr.edu/software/ optimized
Supplementary Information
27
Table 1.11 All the SBs of the optimized models of (1) 7E35-PLpro-C112S-S43-dimer, (2) 7JRNPLpro-wt-GRL0617-dimer, (3) 7LBR-PLpro-wt-XR8-89-dimer, (4) 7RZC-PLpro-wt-Jun9-84-3trimer, and (5) 7SDR-PLpro-wt-Jun9-72-2-trimer (where “X” denotes the same SB appears in the both/all chains of the dimer/trimer) (3) wt-XR8-89-dimer
(4) wt-Jun9-84-3-trimer
(5) wt-Jun9-72-2-trimer
A:GLU168-B:ARG167
A:ASP134-B:LYS6
A:ASP179-C:LYS228
A:ASP179-C:LYS228
B:GLU168-A:ARG167
B:ASP134-A:LYS6
(1) C112S-S43-dimer
(2) wt-GRL0617-dimer
B:GLU161-C:LYS232
B:GLU161-C:LYS232
B:GLU167-C:ARG166
B:GLU167-C:ARG166
A:GLU2-A:ARG4
A:GLU1-A:ARG3
A:GLU1-A:ARG3
B:GLU203-C:LYS157
B:GLU203-C:LYS157
A:ASP63-A:ARG66
A:ASP40-A:LYS43
A:ASP37-A:LYS91
C:GLU161-B:LYS232
C:GLU161-B:LYS232
A:ASP77-A:ARG83
A:GLU51-A:LYS6
A:ASP62-A:ARG65
C:GLU167-B:ARG166
A:GLU168-A:ARG167
A:ASP76-A:ARG82
A:ASP76-A:ARG82
C:GLU203-B:LYS157
A:GLU253-A:LYS298
A:ASP108-A:HIS89
A:GLU143-A:ARG138
A:ASP40-A:LYS43 A:ASP62-A:ARG65
A:ASP287-A:LYS275
A:GLU124-A:LYS306
A:GLU167-A:LYS157
A:GLU51-A:LYS6
A:ASP76-A:ARG82
A:GLU308-A:LYS218
A:GLU143-A:ARG138
A:GLU214-A:LYS217
A:ASP62-A:ARG65
A:GLU124-A:LYS306
A:GLU161-A:LYS157
A:GLU214-A:LYS218
A:ASP76-A:ARG82
A:GLU143-A:ARG138
A:GLU214-A:LYS218
A:GLU238-A:LYS182
A:GLU124-A:LYS306
A:GLU161-A:LYS157
A:GLU252-A:LYS254
A:GLU252-A:LYS254
A:GLU143-A:ARG138
A:ASP164-A:ARG166
A:GLU252-A:LYS297
A:GLU252-A:LYS297
A:GLU161-A:LYS157
A:GLU214-A:LYS217
A:GLU263-A:LYS274
A:GLU280-A:LYS292
A:ASP164-A:ARG166
A:GLU214-A:LYS218
A:GLU280-A:LYS292
A:ASP286-A:HIS272
A:GLU214-A:LYS217
A:GLU238-A:LYS182
A:GLU295-A:LYS297
A:ASP286-A:LYS274
A:GLU252-A:LYS254
A:GLU252-A:LYS254
A:GLU307-A:LYS217
A:GLU295-A:LYS297
A:GLU252-A:LYS297
A:GLU252-A:LYS297
A:GLU280-A:LYS292
A:GLU280-A:LYS292
B:ASP77-B:ARG83 X
J:GLU1-J:ARG3 X
B:GLU1-B:ARG3 X
A:ASP286-A:LYS274
A:ASP286-A:LYS274
B:ASP165-B:ARG167
J:ASP40-J:LYS43 X
B:ASP40-B:LYS43
A:GLU295-A:LYS254
A:GLU295-A:LYS254
B:GLU168-B:LYS158
J:ASP62-J:ARG65
B:ASP62-B:ARG65 X
J:ASP76-J:ARG82 X
B:ASP76-B:ARG82 X
J:GLU143-J:ARG138 X
B:GLU124-B:LYS306
B:GLU51-B:LYS6
B:ASP62-B:ARG65 X
J:GLU161-J:LYS157 X
B:GLU143-B:ARG138 X
B:ASP62-B:ARG65 X
B:ASP40-B:LYS43
B:ASP76-B:ARG82 X
B:ASP40-B:LYS43 X
J:ASP164-J:ARG166
B:GLU167-B:LYS157 X
B:ASP76-B:ARG82 X
B:ASP108-B:HIS89
J:GLU167-J:LYS157
B:ASP179-B:LYS200
B:GLU124-B:LYS306 X
B:GLU124-B:LYS306 X
J:GLU214-J:LYS218 X
B:GLU214-B:LYS218 X
B:GLU143-B:ARG138 X
B:GLU143-B:ARG138 X
J:GLU252-J:LYS254 X
B:GLU252-B:LYS254 X
B:ASP164-B:ARG166 X
B:GLU161-B:LYS157
J:GLU252-J:LYS297 X
B:GLU252-B:LYS297 X
B:GLU214-B:LYS218
B:ASP164-B:ARG166 X
J:GLU280-J:LYS292 X
B:GLU280-B:LYS292 X
B:GLU238-B:LYS182
B:GLU167-B:ARG166
J:ASP286-J:LYS274
B:ASP286-B:LYS274 X
B:GLU252-B:LYS254 X
B:GLU214-B:LYS217
J:GLU295-J:LYS254
B:GLU295-B:LYS297 X
B:GLU252-B:LYS297 X
B:GLU214-B:LYS218 X
J:GLU307-J:LYS217 X
B:GLU307-B:LYS217
B:GLU280-B:LYS292 X
B:GLU252-B:LYS254 X
B:ASP286-B:LYS274
B:GLU252-B:LYS297 X
B:GLU295-B:LYS254 X
B:GLU280-B:LYS292 X
B:GLU307-B:LYS217
B:ASP286-B:LYS274 B:GLU295-B:LYS254 X
C:ASP37-C:LYS91 C:ASP40-C:LYS43
C:ASP37-C:LYS53
C:ASP62-C:ARG65 X
C:ASP40-C:LYS43 X
C:ASP76-C:ARG82 X
C:GLU51-C:LYS6
C:ASP108-C:HIS89
C:ASP62-C:ARG65 X
C:GLU124-C:LYS306 X
C:ASP76-C:ARG82 X
C:GLU143-C:ARG138 X
C:GLU124-C:LYS306 X
C:ASP164-C:ARG166 X
C:GLU143-C:ARG138 X
C:GLU167-C:ARG166
C:ASP164-C:ARG166 X
C:GLU214-C:LYS218
C:GLU214-C:LYS218 X
C:GLU238-C:LYS182
C:GLU238-C:LYS182
C:GLU252-C:LYS254 X
C:GLU252-C:LYS254 X
C:GLU252-C:LYS297 X
C:GLU252-C:LYS297 X
C:GLU263-C:LYS274
C:GLU263-C:LYS274
C:GLU280-C:LYS292 X
C:GLU280-C:LYS292 X
C:GLU295-C:LYS254 X
C:GLU295-C:LYS254 X
C:GLU307-C:LYS217
C:GLU307-C:LYS217
28
1 Papain-Like Cysteine Protease (PLpro)
Fig. 1.13 The Poisson–Boltzmann Electrostatic Potential Surface (EPS) of the models (2) 7JRNPLpro-wt-GRL0617-dimer, (3) 7LBR-PLpro-wt-XR8-89-dimer, (4) 7RZC-PLpro-wt-Jun9-84-3trimer, and (5) 7SDR-PLpro-wt-Jun9-72-2-trimer optimized. For the dimer models (2)–(3) around residues HIS73-THR75 and ASN128-PRO129, there is a large area of negative charge EPS, and for the trimer models (4)–(5) their β-sheets have a large area of positive charge EPS
Table 1.12 All the HBs of the optimized models of (1) 7E35-PLpro-C112S-S43-dimer, (2) 7JRN-PLpro-wt-GRL0617-dimer, (3) 7LBR-PLpro-wt-XR8-89-dimer, (4) 7RZC-PLpro-wtJun9-84-3-trimer, and (5) 7SDR-PLpro-wt-Jun9-72-2-trimer (1) C112S-S43-dimer
(2) wt-GRL0617-dimer
(3) wt-XR8-89-dimer
(4) wt-Jun9-84-3-trimer
(5) wt-Jun9-72-2-trimer
PHE9.N-LYS54.O
LYS6.N-GLU51.OE1
ARG3.NE-GLU1.OE1
LYS6.N-GLU51.OE1
ARG3.NH2-ASN48.OD1
THR10.N-GLN20.OE1
VAL7.N-GLN19.O
PHE8.N-LYS53.O
LYS6.NZ-GLU51.OE2
LYS6.N-GLU51.OE1
ASP13.N-THR11.OG1
PHE8.N-LYS53.O
ASP12.N-THR10.OG1
PHE8.N-LYS53.O
LYS6.N-GLU51.OE2
ASN16.N-ASP13.OD1
ASN13.N-THR10.OG1
ASN13.N-THR10.OG1
ILE14.N-ASP12.OD1
PHE8.N-LYS53.O
ASN16.ND2-GLU68.OE2
ILE14.N-ASP12.OD1
ILE14.N-ASP12.OD1
ASN15.ND2-ASP12.OD2
ILE14.N-ASP12.OD1
HIS18.N-THR10.O
ASN15.N-ASP12.OD1
ASN15.N-ASP12.OD1
HIS17.N-THR9.O
ASN15.ND2-ASP12.OD2
GLN20.N-VAL8.O
LEU16.N-LEU16.O
LEU16.N-LEU16.O
GLN19.N-VAL7.O
HIS17.N-THR9.O
VAL22.N-ILE6.O
HIS17.N-THR9.O
HIS17.N-THR9.O
GLN19.NE2-THR9.OG1
GLN19.N-VAL7.O
MET24.N-ARG4.O
HIS17.ND1-ASN15.OD1
THR18.N-ILE14.O
VAL21.N-ILE5.O
GLN19.NE2-THR9.OG1
GLN31.N-TYR28.O
GLN19.N-VAL7.O
GLN19.N-VAL7.O
SER24.N-ASP22.OD2
VAL21.N-ILE5.O
PHE32.N-TYR28.O
GLN19.NE2-THR9.OG1
MET23.N-ARG3.O
GLN29.N-THR26.O
SER24.N-ASP22.OD1
TYR36.N-TYR57.O
MET23.N-ARG3.O
SER24.N-ASP22.OD1
GLN30.NE2-THR26.O
GLN30.NE2-THR26.O
ALA40.N-LEU37.O
SER24.N-ASP22.OD1
GLN29.N-THR26.O
GLN30.N-TYR27.O
PHE31.N-TYR27.O
VAL42.N-THR35.O
GLN30.NE2-THR26.O
GLN30.N-TYR27.O
PHE31.N-TYR27.O
TYR35.N-TYR56.O
HIS48.ND1-SER50.OG
PHE31.N-TYR27.O
PHE31.N-TYR27.O
TYR35.N-TYR56.O
VAL41.N-THR34.O
HIS51.N-HIS48.O
TYR35.N-TYR56.O
THR34.N-THR42.OG1
VAL41.N-THR34.O
THR42.N-ASP40.OD1
GLY53.N-LYS7.O
VAL41.N-THR34.O
TYR35.N-TYR56.O
THR42.N-ASP40.OD1
LYS43.NZ-ASP40.OD2
LYS54.N-HIS51.O
THR42.N-ASP40.OD1
VAL41.N-THR34.O
LYS43.NZ-ASP40.OD2
LYS45.NZ-SER24.O
PHE56.N-PHE9.O
LYS43.NZ-ASP40.OD2
THR42.N-ASP40.OD1
LYS45.NZ-SER24.O
HIS50.ND1-TYR27.OH
VAL58.N-THR11.O
LYS45.NZ-SER24.O
LYS43.NZ-ASP40.OD2
HIS47.ND1-SER49.OG
HIS50.N-HIS47.O
ALA69.N-LEU65.O
HIS47.ND1-SER49.OG
LYS45.NZ-SER24.O
HIS50.ND1-TYR27.OH
GLY52.N-LYS6.O
GLU68.N-THR64.O
HIS50.ND1-TYR27.OH
HIS50.ND1-TYR27.OH
HIS50.N-HIS47.O
LYS53.N-HIS50.O
VAL67.N-ASP63.O
GLY52.N-LYS6.O
LYS53.N-HIS50.O
GLY52.N-LYS6.O
THR63.N-ASP61.OD1
GLU71.N-VAL67.O
LYS53.N-HIS50.O
LEU64.N-ASP61.OD1
PHE55.N-PHE8.O
LEU64.N-ASP61.OD2
TYR72.OH-ASP135.OD1
LEU64.N-ASP61.OD1
ARG65.NE-ASP62.OD2
ASN60.ND2-LEU58.O
GLU70.N-VAL66.O
TYR84.N-PHE80.O
ALA68.N-LEU64.O
GLU67.N-THR63.O
THR63.N-ASP61.OD2
TYR71.N-GLU67.O
ALA87.N-ARG83.O
GLU70.N-VAL66.O
ALA68.N-LEU64.O
LEU64.N-ASP61.OD1
TYR72.OH-VAL11.O
LEU88.N-TYR84.O
TYR71.OH-ASP134.OD2
GLU70.N-VAL66.O
VAL66.N-THR63.O
HIS73.N-PHE69.O
HIS90.N-ALA87.O
TYR72.N-ALA68.O
TYR72.N-ALA68.O
GLU70.N-VAL66.O
ARG82.NH2-ASP76.OD2
THR91.N-ALA87.O
ARG82.NH2-ASP76.OD2
ARG82.NH2-ASP76.OD2
TYR71.OH-ASP134.OD2
ARG82.NE-SER78.OG
LYS92.NZ-ASP38.O
ARG82.NE-SER78.OG
ARG82.NE-SER78.OG
HIS73.N-PHE69.O
TYR83.N-PHE79.O
LYS93.N-HIS90.O
TYR83.N-PHE79.O
ARG82.NH1-ALA153.O
ARG82.NH2-ASP76.OD2
MET84.N-LEU80.O
TRP94.NE1-ASP109.OD2
MET84.N-LEU80.O
TYR83.N-PHE79.O
ARG82.NE-SER78.OG
ALA86.N-ARG82.O
TYR96.OH-THR91.O
SER85.N-GLY81.O
MET84.N-LEU80.O
ARG82.NH1-ALA153.O
LEU87.N-TYR83.O
VAL99.N-LEU102.O
ALA86.N-ARG82.O
SER85.N-GLY81.O
TYR83.N-PHE79.O
HIS89.ND1-SER85.O
THR103.OG1-ALA140.O
LEU87.N-TYR83.O
ALA86.N-ARG82.O
MET84.N-LEU80.O
HIS89.N-ALA86.O
SER104.N-PRO97.O
TRP93.NE1-ASP108.OD2
LEU87.N-TYR83.O
SER85.N-GLY81.O
HIS89.ND1-ASP108.OD2
LYS106.N-LYS95.O
TYR95.OH-THR90.O
LYS91.NZ-ASP37.O
LEU87.N-TYR83.O
LYS92.NZ-ASN88.O
ASN111.N-ALA108.O
GLN97.NE2-THR102.OG1
LYS91.NZ-ASP37.OD2
HIS89.N-ALA86.O
TRP93.NE1-ASP108.OD2
ASN111.ND2-LYS106.O
THR102.N-GLN121.OE1
TRP93.NE1-ASP108.OD2
LYS91.NZ-ASP37.OD2
VAL98.N-LEU101.O
GLN122.NE2-THR103.O
THR102.OG1-ALA139.O
TYR95.OH-THR90.O
LYS92.NZ-ASN88.O
THR102.OG1-ALA139.O
GLN122.NE2-LEU118.O
SER103.N-PRO96.O
GLN97.NE2-THR102.OG1
TRP93.NE1-ASP108.OD2
SER103.N-PRO96.O
ASN129.N-HIS176.O
LYS105.N-LYS94.O
THR102.OG1-ALA139.O
THR102.N-GLN121.OE1
LYS105.N-LYS94.O
ALA132.N-TYR72.O
ASN109.ND2-GLY160.O
SER103.N-PRO96.O
THR102.OG1-ALA139.O
ASN109.ND2-GLY160.O
ASP135.N-PRO131.O
ASN110.ND2-LYS105.O
LYS105.N-LYS94.O
SER103.N-PRO96.O
ASN110.ND2-LYS105.O
TYR138.N-GLN134.O
ASN110.N-ALA107.O
ASN109.ND2-GLY160.O
LYS105.N-LYS94.O
ASN110.N-ALA107.O
ASN147.ND2-TYR84.OH
LEU117.N-LEU113.O
ASN110.N-ALA107.O
ASN109.ND2-GLY160.O
THR115.N-CYS111.O
CYS149.N-ALA145.O
GLN121.NE2-THR102.O
THR115.N-CYS111.O
ASN110.N-ALA107.O
LEU117.N-LEU113.O
ILE152.N-PHE148.O
GLN121.NE2-LEU117.O
LEU117.N-LEU113.O
ASN110.ND2-LYS105.O
LEU118.N-ALA114.O
TYR155.OH-TYR73.O
GLN122.N-THR119.O
LEU120.N-ALA116.O
THR115.N-CYS111.O
THR119.N-THR115.O
CYS156.N-ILE152.O
ASN128.N-HIS175.O
GLN121.NE2-LEU117.O
LEU117.N-LEU113.O
LEU120.N-ALA116.O
LYS158.N-LEU153.O
ALA131.N-TYR71.O
GLN122.NE2-LEU118.O
LEU118.N-ALA114.O
GLN121.NE2-THR102.O
THR159.N-GLU162.OE1
ASP134.N-PRO130.O
GLN122.N-THR119.O
GLN121.NE2-THR102.O
GLN121.NE2-LEU117.O
VAL166.N-TYR274.OH
GLY142.N-ARG138.O
ILE123.N-THR119.O
GLN121.NE2-LEU117.O
GLN122.N-THR119.O
ARG167.NH1-GLU168.OE1
ASN146.ND2-TYR83.OH
ALA131.N-TYR71.O
GLN122.N-THR119.O
ASN128.N-HIS175.O
GLU168.N-ASP165.OD2
CYS148.N-ALA144.O
TYR136.N-LEU132.O
LYS126.NZ-GLN133.OE1
ALA131.N-TYR71.O
MET170.N-VAL166.O
TYR154.N-LEU150.O
ARG138.NE-GLU143.OE1
ASN128.ND2-HIS175.O
ASP134.N-PRO130.O
SER171.N-ARG167.O
LYS157.NZ-GLU161.OE2
ARG138.NH1-GLU143.OE2
ASN128.N-HIS175.O
ARG138.NH2-ASN146.OD1
ASN178.N-LYS127.O
ASP164.N-GLU167.OE1
ARG138.NH2-GLU143.OE2
ALA131.N-TYR71.O
GLY142.N-ALA139.O
ARG184.N-LEU200.O
THR168.N-ASP164.O
CYS148.N-ALA144.O
ASP134.N-PRO130.O
CYS148.N-ALA144.O
VAL185.N-GLN237.O
MET169.N-VAL165.O
ILE151.N-PHE147.O
ARG138.N-ASP134.O
TYR154.N-LEU150.O
ASN187.ND2-GLN195.OE1
SER170.N-ARG166.O
TYR154.OH-TYR72.O
ARG138.NE-GLU143.OE1
CYS155.N-ILE151.O
GLN196.NE2-CYS193.O
ASN177.N-LYS126.O
TYR154.N-LEU150.O
ARG138.NH1-GLU143.OE1
LYS157.N-LEU152.O
THR198.N-LEU186.O
CYS181.N-LEU178.O
CYS155.N-ILE151.O
ARG138.NH1-GLU143.OE2
LYS157.NZ-GLU161.OE2
ALA205.N-GLY202.O
LYS182.N-GLU238.O
LYS157.NZ-GLU167.OE2
ARG138.NH2-GLU143.OE2
ASP164.N-GLU167.OE2
MET207.N-VAL203.O
ARG183.NE-GLN237.OE1
THR158.N-GLU161.OE1
CYS148.N-ALA144.O
ARG166.NH1-GLU167.OE2
LYS218.NZ-GLU308.OE1
VAL184.N-GLN236.O
THR168.N-ASP164.O
ILE151.N-PHE147.O
ARG166.NH2-GLU167.OE1
GLY220.N-GLN216.O
LEU185.N-THR197.O
MET169.N-VAL165.O
LEU152.N-CYS148.O
THR168.N-ASP164.O
VAL221.N-LYS233.O
ASN186.ND2-GLN194.OE1
CYS181.N-LEU178.O
TYR154.N-LEU150.O
MET169.N-VAL165.O
ILE223.N-ALA231.O
ASN186.ND2-TYR233.OH
LEU185.N-THR197.O
LYS157.N-LEU152.O
GLN174.NE2-SER170.O
VAL236.N-VAL185.O
VAL187.N-GLN195.O
ASN186.ND2-GLN196.OE1
LYS157.NZ-GLU203.OE1
ASN177.N-LYS126.O
Table 1.13 All the HBs of the optimized models of (1) 7E35-PLpro-C112S-S43-dimer, (2) 7JRN-PLpro-wt-GRL0617-dimer, (3) 7LBR-PLpro-wt-XR8-89-dimer, (4) 7RZC-PLpro-wtJun9-84-3-trimer, and (5) 7SDR-PLpro-wt-Jun9-72-2-trimer (continuation) (1) C112S-S43-dimer
(2) wt-GRL0617-dimer
(3) wt-XR8-89-dimer
(4) wt-Jun9-84-3-trimer
(5) wt-Jun9-72-2-trimer
ALA231.N-ILE223.O
GLY193.N-CYS189.O
VAL187.N-GLN195.O
THR158.N-GLU203.OE2
ASN177.ND2-ASP179.OD1
TYR234.N-ASN187.O
GLN195.N-VAL187.O
VAL188.N-THR231.O
ARG166.NE-ASP164.OD2
CYS181.N-LEU178.O
TYR234.CD1-LYS233.C
LEU199.N-ARG183.O
CYS189.N-GLY193.O
THR168.N-ASP164.O
ARG183.NE-GLN237.OE1
LEU235.N-PHE217.O
LYS200.NZ-ASP179.O
THR197.N-LEU185.O
MET169.N-VAL165.O
VAL184.N-GLN236.O
GLN238.N-TYR311.O
GLN215.NE2-GLY219.O
LYS200.N-GLU203.OE1
SER170.N-ARG166.O
LEU185.N-THR197.O
GLU239.N-LYS183.O
LYS217.NZ-GLU307.OE1
MET206.N-VAL202.O
ASN177.N-LYS126.O
ASN186.ND2-GLN194.OE1
MET245.N-VAL304.O
GLU203.N-GLU203.OE1
TYR207.OH-LYS232.NZ
ARG183.NE-GLN237.OE1
ASN186.ND2-TYR233.OH
GLN251.N-GLN251.OE1
MET206.N-VAL202.O
TYR213.OH-GLU307.OE1
VAL184.N-GLN236.O
VAL187.N-GLN195.O
THR260.N-PHE305.O
GLY219.N-GLN215.O
GLN215.NE2-GLY219.O
ASN186.ND2-GLN194.OE1
CYS189.N-GLY193.O
TYR265.OH-ASN268.O
ILE222.N-ALA230.O
LYS217.NZ-GLU307.OE2
ASN186.ND2-TYR233.OH
GLY193.N-CYS189.O
THR266.N-HIS273.O
ALA230.N-ILE222.O
GLY219.N-GLN215.O
VAL187.N-GLN195.O
GLN194.NE2-LYS315.O
ASN268.N-CYS271.O
LYS232.NZ-TYR207.OH
ILE222.N-ALA230.O
CYS189.N-GLY193.O
GLN196.NE2-GLN250.OE1
GLN270.N-ASN268.OD1
VAL235.N-VAL184.O
GLN229.NE2-GLN221.OE1
GLN195.NE2-GLN196.O
THR198.N-GLY266.O
LYS275.N-GLU264.O
GLN236.NE2-GLU238.OE2
ALA230.N-ILE222.O
GLN196.NE2-GLN250.OE1
LEU199.N-ARG183.O
HIS276.N-ILE286.O
GLN237.NE2-ALA204.O
LYS232.NZ-TYR207.OH
THR197.N-LEU185.O
LYS200.N-GLU203.OE1
ILE277.N-ALA262.O
GLU238.N-LYS182.O
VAL235.N-VAL184.O
LEU199.N-ARG183.O
LYS200.NZ-CYS181.O
SER279.N-THR260.O
MET243.N-VAL205.O
GLN236.NE2-THR311.OG1
LYS200.NZ-ASP179.O
LYS200.NZ-SER180.O
LYS280.NZ-ASN100.OD1
MET244.N-VAL303.O
GLN237.NE2-ALA204.O
VAL205.N-VAL202.O
VAL205.N-VAL202.O
LYS280.N-THR282.O
SER245.N-TYR207.O
GLN237.NE2-SER239.OG
MET206.N-VAL202.O
MET206.N-VAL202.O
GLU281.N-GLU281.OE1
TYR251.N-GLY298.O
GLU238.N-LYS182.O
TYR207.OH-LYS232.NZ
GLY209.N-SER245.O
ILE286.N-HIS276.O
THR259.N-PHE304.O
SER239.N-ASN308.O
GLN215.NE2-GLY219.O
TYR213.OH-GLU307.OE1
ASP287.N-LEU290.O
LYS274.NZ-GLU263.OE1
MET243.N-VAL205.O
LYS217.NZ-GLU214.OE2
GLN215.NE2-GLY219.O
LEU290.N-ASP287.O
LYS274.NZ-ASP286.OD2
MET244.N-VAL303.O
LYS217.NZ-GLU307.OE1
LYS217.NZ-GLU214.OE2
THR292.N-CYS285.O
ILE276.N-ALA261.O
SER245.N-TYR207.O
LYS218.N-GLN215.O
LYS217.NZ-GLU307.OE1
TYR297.CE2-GLU264.OE2
LYS279.NZ-ASN99.OD1
THR259.N-PHE304.O
GLY219.N-GLN215.O
LYS218.NZ-GLU214.OE1
THR302.N-SER263.O
LYS279.N-THR281.O
TYR264.N-PRO299.O
VAL220.N-LYS232.O
GLY219.N-GLN215.O
PHE305.N-CYS261.O
TYR283.N-THR277.O
LYS274.NZ-ASP286.OD2
GLN221.NE2-GLN174.OE1
VAL220.N-LYS232.O
TYR306.OH-LEU212.O
TYR283.OH-GLU280.OE1
HIS275.N-ILE285.O
ILE222.N-ALA230.O
GLN221.NE2-GLN229.OE1
TYR306.N-VAL243.O
ASP286.N-LEU289.O
SER278.N-THR259.O
LYS228.NZ-ASN177.OD1
ILE222.N-ALA230.O
LEU289.N-ASP286.O
LYS279.N-THR281.O
LYS228.NZ-THR191.OG1
ALA230.N-ILE222.O
TYR296.OH-GLU263.OE2
TYR283.N-THR277.O
GLN229.N-ASP179.OD1
LYS232.NZ-GLU161.OE1
LYS297.NZ-GLU252.OE2
TYR283.OH-GLU280.OE1
ALA230.N-ILE222.O
LYS232.NZ-TYR207.OH
VAL303.N-MET244.O
ILE285.N-HIS275.O
LYS232.NZ-TYR207.OH
VAL235.N-VAL184.O
PHE304.N-CYS260.O
ASP286.N-LEU289.O
LYS232.NZ-GLN269.OE1
GLN236.NE2-THR311.OG1
TYR305.OH-LEU211.O
LEU289.N-ASP286.O
VAL235.N-VAL184.O
GLN237.NE2-ALA204.O
THR291.N-CYS284.O
GLN237.NE2-ALA204.O
GLN237.NE2-SER239.OG
LYS292.NZ-GLU280.OE2
GLN237.NE2-SER239.OG
GLU238.N-LYS182.O
SER293.N-LEU282.O
GLU238.N-LYS182.O
MET243.N-VAL205.O
TYR296.OH-GLU263.OE2
MET243.N-VAL205.O
MET244.N-VAL303.O
LYS297.NZ-GLU252.OE1
MET244.N-VAL303.O
SER245.N-TYR207.O
THR301.N-SER262.O
SER245.N-TYR207.O
LEU253.N-TYR296.O
PHE304.N-CYS260.O
LEU253.N-TYR296.O
LYS254.NZ-GLU252.OE2
TYR305.N-VAL242.O
LYS254.NZ-GLU252.OE1
LYS254.NZ-GLU295.OE1
THR259.N-PHE304.O
THR259.N-PHE304.O
TYR264.OH-ASN267.O
TYR264.OH-ASN267.O
GLY266.N-THR225.O
GLY266.N-THR225.O
ASN267.N-CYS270.O
ASN267.N-CYS270.O
GLN269.NE2-MET208.O
GLN269.N-ASN267.OD1
GLN269.NE2-GLY209.O
LYS274.NZ-GLU263.OE1
GLN269.N-ASN267.OD1
LYS274.NZ-ASP286.OD2
LYS274.N-GLU263.O
ILE276.N-ALA261.O
LYS274.NZ-GLU263.OE1
LYS279.NZ-ASN99.OD1
LYS274.NZ-ASP286.OD2
LYS279.N-THR281.O
ILE276.N-ALA261.O
TYR283.N-THR277.O
LYS279.NZ-ASN99.OD1
TYR283.OH-GLU280.OE1
LYS279.N-THR281.O
ILE285.N-HIS275.O
TYR283.N-THR277.O
ASP286.N-LEU289.O
TYR283.OH-GLU280.OE1
LEU289.N-ASP286.O
ILE285.N-HIS275.O
THR291.N-CYS284.O
ASP286.N-LEU289.O
LYS292.NZ-TYR283.OH
LEU289.N-ASP286.O
TYR296.OH-GLU263.OE2
THR291.N-CYS284.O
LYS297.NZ-GLU252.OE2
TYR296.OH-GLU263.OE2
THR301.N-SER262.O
LYS297.NZ-GLU252.OE2
VAL303.N-MET244.O
THR301.N-SER262.O
PHE304.N-CYS260.O
VAL303.N-MET244.O
TYR305.N-VAL242.O
PHE304.N-CYS260.O
ASN308.N-GLU307.OE2
TYR305.N-VAL242.O
TYR310.N-GLN237.O
LYS306.NZ-GLU124.OE1
TYR310.OH-LEU234.O
LYS306.NZ-GLU124.OE2 TYR310.N-GLN237.O LYS315.NZ-LYS315.N
Supplementary Information
31
Table 1.14 All the residues of the optimized models of (1) 7E35-PLpro-C112S-S43-dimer, (2) 7JRN-PLpro-wt-GRL0617-dimer, (3) 7LBR-PLpro-wt-XR8-89-dimer, (4) 7RZC-PLpro-wtJun9-84-3-trimer, and (5) 7SDR-PLpro-wt-Jun9-72-2-trimer that bind with the ions Zn2+ and their respective inhibitors (2) wt-GRL0617-dimer
(1) C112S-S43-dimer A:ZN401
A:CYS190, A:THR192, A:CYS193,
A:ZN402
(3) wt-XR8-89-dimer A:ZN401
A:CYS224, A:THR225, A:CYS226.
A:CYS225, A:THR226, A:CYS227. B:ZN401
A:CYS189, A:THR191, A:CYS192,
B:CYS190, B:THR192, B:CYS193,
B:ZN401
A:GLU158,
B:CYS189, B:THR191, B:CYS192, B:CYS224, B:THR225, B:CYS226,
B:CYS225, B:THR226, B:CYS227. A:GYX402
A:CYS189, A:THR191, A:CYS192, A:CYS224, A:CYS226, A:LYS228.
A:TTT401
A:LEU163,
A:LEU162,
B:LYS228.
A:GLY163,
A:ASP165,
A:ASP164,
A:ARG167,
A:MET208,
A:X77-404
A:GLY163,
A:LEU162,
A:PRO248,
A:PRO248,
A:ASP164,
A:PRO249,
A:TYR264,
A:GLU167,
A:TYR265,
A:TYR268,
A:PRO247,
A:ASN268,
A:GLN269,
A:PRO248,
A:TYR269,
A:TYR273,
A:TYR264,
A:TYR274,
A:THR301.
A:GLY266,
A:THR302,
A:TYR268,
B:MET209,
A:GLN269,
B:GLY210,
A:TYR273,
B:ALA247,
A:THR301.
B:PRO248, B:SER246, B:TYR269. B:GYX402
A:TYR208,
B:X77-404
B:LEU162,
A:TYR269,
B:GLY163,
B:GLU162,
B:ASP164,
B:LEU163,
B:GLU167,
B:GLY164,
B:PRO248,
B:ASP165,
B:ALA249,
B:PRO249,
B:TYR264,
B:TYR265,
B:GLY266,
B:ASN268,
B:ASN267,
B:TYR269,
B:TYR268,
B:TYR274,
B:GLN269, B:TYR273,
B:PRO248,
B:THR301.
B:THR302. (4) wt-Jun9-84-3-trimer A:ZN502
A:CYS189, A:THR191, A:CYS192,
B:ZN502
B:CYS189, B:CYS192,
(5) wt-Jun9-72-2-trimer A:ZN502
A:CYS189, A:THR191, A:CYS192,
B:ZN502
B:CYS189, B:THR191, B:CYS192,
A:CYS224, A:CYS226.
A:CYS224, A:CYS226. B:CYS224, C:CYS226, C:LYS228. C:ZN502
C:CYS189, C:CYS192,
B:CYS224, B:CYS226. C:ZN502
C:CYS189, C:THR191, C:CYS192,
A:JW9-501
A:LYS157,
C:CYS224, C:THR225, C:CYS226. A:JWX501
B:LYS157,
A:MET209,
A:LEU162,
C:CYS224, C:CYS226.
A:ASP164,
A:LEU162,
A:GLU167,
A:GLY163,
A:MET208,
A:ASP164,
A:PRO248,
A:GLU167,
A:TYR264,
A:PRO248,
A:ASN267,
A:TYR264,
A:TYR268,
A:ASN267,
A:TYR273.
A:TYR268, A:TYR273.
(continued)
32
1 Papain-Like Cysteine Protease (PLpro)
Table 1.14 (continued) (1) C112S-S43-dimer B:JWX501
A:GLN195,
(2) wt-GRL0617-dimer B:JW9-501
A:GLN195,
B:LEU162,
A:THR197,
B:GLY163,
B:LYS157,
B:ASP164,
B:LEU162,
B:ARG166,
B:GLY163,
B:GLU167,
B:ASP164,
B:MET208,
B:PRO248,
B:PRO247,
B:TYR264,
B:PRO248,
B:ASN267,
B:TYR264,
B:TYR268,
B:ASN267,
B:TYR273,
B:TYR268,
C:TYR268.
B:TYR273, B:THR301, C:TYR268. C:JWX501
A:THR225,
C:JW9-501
B:TYR268,
B:ARG166,
C:LYS157,
B:TYR268,
C:LEU162,
C:LEU162,
C:GLY163,
C:GLY163,
C:ASP164,
C:ASP164,
C:GLU167,
C:GLU167,
C:TYR264,
C:MET208,
C:ASN267,
C:PRO248,
C:TYR268,
C:TYR264,
C:TYR273,
C:ASN267,
C:THR301.
C:TYR268, C:TYR273.
(3) wt-XR8-89-dimer
Chapter 2
3C-Like Protease (3CLpro)
Abstract The 3C-like protease (or called the main protease) of COVID-19 is a critical enzyme for the maturation of viral particles and a potential target for antiviral drugs. This chapter firstly did the work skillfully by locally optimizing the structures of SARS-CoV-2 3C-like protease (3CLpro) in complex with its inhibitor, N3/carmofur (6LU7.pdb & 7BQY.pdb/7BUY.pdb), from COVID-19 virus; then some new structural bioinformatics from the structures optimized for developing therapies of the currently fatal COVID-19 virus are reported. Currently, lots of researchers are using optimization to screen, dock, find, and design new therapies for COVID-19 but it is not used professionally. The hybrid strategy of mathematical optimization’s neighboring different (local search) algorithms is used professionally in this chapter. The X-ray crystallography structure for the COVID-19 3CLpro with unliganded active site was also released into the Protein Data Bank (PDB) with PDB entry 6Y84; this chapter will also study the dimer 3CLpro (with unliganded active site/without the ligand N3) by optimization and molecular dynamics (MD) techniques. The 3CLpro variants delP168, a173v, delP168, and a173v are also studied by optimization and MD techniques. In common, from almost all the models of the 3CLpro dimer, we found that sometimes, there are two strong polar contacts between GLU290 and ARG4 linking the two monomers. In comparison, we also study the SARS-CoV-1-Mpro and SARS-CoV-1-Mpro-N3 in this chapter by optimization and MD techniques. Keywords COVID-19 virus · 3C-Like protease (3CLpro) · Optimizing their structures · Molecular dynamics · Monomer and dimer · Structural bioinformatics
2.1 Introduction The COVID-19 virus 3CLpro is a key coronavirus enzyme that plays a pivotal role in mediating viral replication and transcription, making it an attractive drug (e.g., N3, carmofur) target for this virus [160]. The X-ray crystallography structures for © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_2
33
34
2 3C-Like Protease (3CLpro)
3CLpro-N3 (with PDB entries 6LU7 and 7BQY) were recently released into the PDB (www.rcsb.org). The dimer of 3CLpro (with unliganded active site) has been reported to be the best option of drug targets against the COVID-19 virus and its Xray structure was also released into the PDB with PDB entry 6Y84 [259]. This brief chapter will also study these (monomeric and dimeric) structures optimized through MD computations in order to seek additional useful structural bioinformatics for developing therapies of the currently fatal COVID-19.
2.2 Materials and Methods 2.2.1 Monomer The materials used in this chapter are the PDB entries 6LU7 and 7BQY. The methods are used to optimize their structures and to confirm the bioinformatics of optimized structures from the analyses of MD trajectory datasets. The hybrid strategy of mathematical optimization’s neighboring different algorithms is completely the same as the one used in [405, 413]. We optimized the structures locally and slightly, looking at the optimization problem as a three-body problem. The decreased energies (KJ/mol) are .−13411.358 (E3), .−13734.746 (E6), and .−13988.698 (E9) for 6LU7.pdb and .−12957.118 (E3), .−13285.783 (E6), and .−13550.220 (E9) for 7BQY.pdb, respectively. The RMSD (Chapter 1 of [412]) values of the optimized structures from the original structures are 1.456041 Å for 6LU7.pdb and 1.286947 Å for 7BQY.pdb, respectively; thus, the optimized 3CLproN3 structures are as good as their original structures. The differences of the 3D structure and secondary structure between each optimized and original structures can be detected by the package MOLMOL [184] and its CalcSecondary output files produced.
2.2.2 Dimer The MD materials and methods for the dimer of COVID-19 3CLpro with unliganded active site can be seen from [321] (with data ID DESRES-ANTON10880334): “This trajectory is from a 100 .μs MD simulation of the apo enzyme started from the apo enzyme structure determined by X-ray crystallography (PDB entry 6Y84). The protein was solvated in a .120 × 120 × 120 Å water box containing 0.15 M NaCl. The simulation was performed on Anton 2 using the DES-Amber force field. The interval between frames is 1 ns. The simulation was conducted at 300 K in the NPT ensemble.” We denote the model as the 6Y84-dimer model. The MD materials and methods of the dimeric SARS-Cov-2 3CLpro without any ligand can be seen from [180]: The starting structure was prepared based on
2.3 Results and Discussions
35
6LU7.pdb with amber99sb-ildn force field; the MD was done using GROMACS under NVT at 310 K, with time-size about 2.5 fs, the MD system composed of 98,694 atoms in 9.98921 nm length cubic box with periodic boundary conditions, and the two sets of 10 .μs MD trajectories were done with different random seeds for the preparation of solvent and the production runs. We denote the model as the 6LU7-dimer model. In [113] we find three sets of 50 ns’ REMD trajectories for the dimeric SARSCoV-2 3CLpro without any ligand. We denote the model as the Evans-dimer model. In [346] the MD trajectories are presented for SARS-CoV-1 and SARS-CoV2 main proteases in monomeric/dimeric and apo/holo states, where the MD simulations are built on the four PDB entries 1q2w (SARS-CoV-1-Mpro), 6y2e (SARS-CoV-2-Mpro), 2hob (SARS-CoV-1-Mpro with ligand N3), and 6lu7 (SARSCoV-2-Mpro with ligand N3, where 6lu7-monomer/dimer without ligand MDdatabases can also be gotten now). The 3CLpro variants delP168, a173v, delP168, and a173v are also 17 studied by optimization (Tables 2.1 and 2.2) and MD techniques.
2.3 Results and Discussions 2.3.1 Monomer We report some new findings from our optimized structures. Let us analyze our optimized structures of 6LU7 and 7BQY. We set the hydrogen bond (HB) donor-acceptor distance cutoff to 3.0 Å and the angle cutoff to 20 degrees. We found the following HBs for both 6LU7optimized and 7BQYoptimized models: C:Val3.O-A:Glu166.H, C:Val3.H-A:Glu166.O, C:Leu4.H-A:Gln189.OE1, C:Ala2.H-A:Thr190.O, and C:010 6.O-A:Gly143.N for 6LU7optimized model and C:PJE101.O7-A:Cys145.H for 7BQYoptimized model. For 6LU7optimized model, we confirm these HBs by the 100 ns’ molecular dynamics (MD) productions of [102]: A:GLU166.N-C:VAL3.O with 30.07% occupancy rate, C:VAL3.NA:GLU166.O with 26.67% occupancy rate, A:HIE41.NE2-C:LEU4.O with 0.10% occupancy rate, C:ALA2.N-A:THR190.O with 3.20% occupancy rate, C:ALA2.NA:GLN192.O with 3.40% occupancy rate, and A:GLN189.NE2-C:ALA2.O with 5.69% occupancy rate . For the A-chain (i.e., 3CLpro), its main HBs with occupancy rates greater than 50% can be seen from Table 2.3. For both 6LU7optimized and 7BQYoptimized 3CLpros, we find that there are four .π -.π stackings HIS163-PHE140-HIS172-HIS163, TYR37-PHE103, and one + .π -cation ARG. 298.NH2-PHE8. We found out the following salt bridges (SBs) (oxygen-nitrogen cutoff: 3.2 Å) for 3CLpro during the 100 ns’ MD production phase of [102]: GLU55-ARG40, ASP295-ARG298, ASP229-LYS269, ASP289-ARG131, ASP197-LYS137, ASP197-ARG131, ASP153-ARG298, GLU47-ARG60, ASP48-LYS61, ASP155-LYS12, ASP176-ARG105, GLU290-LYS137, ASP92-ARG76, GLU14-LYS97, GLU290-LYS5, GLU288-LYS5, GLU270-LYS269, ASP48-ARG60, ASP263-ARG222, GLU290-ARG131,
36
2 3C-Like Protease (3CLpro)
ASP187-ARG40, ASP155-LYS100, ASP34-LYS90, ASP153-LYS102, and GLU288-LYS137.
Among them, (i) GLU290-ARG131, GLU228-LYS137, GLU55-ARG40, GLU47ARG60, GLU14-LYS97, ASP295-ARG298, ASP263-ARG222, ASP176-ARG105, ARG153-ARG298, and ASP155-LYS12 are always broken during the 100 ns of MD; (ii) ARG92-ARG76 exists during 76–100 ns, ASP48-LYS61 exists during 86–100 ns, and ASP229-LYS269 exists during 33–48 ns; (iii) ASP153LYS102, ASP48-ARG60, ARG197-ARG131 (broken during most of the time), and GLU270-LYS269 are weak but last longer during the whole 100 ns of MD; (iv) ARG289-ARG131, ASP187-ARG40, ASP187-ARG40, ASP34-LYS90, ASP197LYS137 (18–40 ns), ASP155-LYS100 (72–82 ns broken), and GLU288-LYS5 (GLU290-LYS95 is weak) are maintained during the 100 ns’ MD production. Some SBs are shown in Fig. 2.17 (where the x-axis is the MD production time, 100 ns, and y-axis is the distance (Å))—for each SB’s two residues, the numbers of residues that spanned are 56, 55, 147, 60, 158, 283, and 285, respectively. The SBs ASP155-LYS100 and ASP187-ARG40 strongly maintain the binding pocket for N3. For the optimized N3-3CLpro, its Ramachandran plots for 6LU7optimized and 7BQYoptimized models are shown in Fig. 2.1, where we can see that there is a slight difference between the 6LU7optimized and BQY7optimized models. The Ramachandran plots with large percentage of residues in most favored regions might reveal that 3CLpro protein structures are suitable for docking studies with the compounds.
Fig. 2.1 The Ramachandran plot for the 6LU7optimized model (left) and the 7BQYoptimized model (right)
For the 6LU7optimized model and 7BQYoptimized model, let us look at their N3-3CLpro interaction diagrams (Figs. 2.2 and 2.3) (there is a slight difference between these two diagrams). The compound N3 consists of the three strictly hydrophobic residues ALA2-VAL3-LEU4, and it is surrounded by the hydrophobic residues LEU27, PHE140, LEU141, MET165, PRO168, and ALA191 (thus forming a small hydrophobic pocket); the polar residues HIS, ASN142, SER144, and THR190, the charged residue GLU166; etc. (thus forming a binding site).
2.3 Results and Discussions
37
Fig. 2.2 The N3-3CLpro interaction diagram for the 6LU7optimized model
Fig. 2.3 The N3-3CLpro interaction diagram for the 7BQYoptimized model
For the 100 ns’ MD productions, from the secondary structure development (with RMSF (Chapter 1 of [412]) values for each residue (Fig. 2.4)), we can see some secondary structural changes in segments 10–16, 46–50, 46–50, 181–200, 235–238, and 285–300 (Fig. 2.18) during the whole 100 ns’ MD, and for the RMSD, we know that during 28–100 ns, the protein equilibrates around an RMSD value of 2.1 Å (Fig. 2.4). Larger RMSF variations (Fig. 2.4) are at N- and C-terminals and segments 218–228, 48–58, and 188–198 (during 54–100 ns).
38
2 3C-Like Protease (3CLpro)
Fig. 2.4 The RMSF and RMSD for the 6LU7optimized model during 100 ns’ MD
Similarly, the newly released 3CLpro-carmofur structure 7BUY.pdb [161] is optimized and studied as follows. The decreasing energies (KJ/mol) of optimizing the 7BUY.pdb structure are .−12014.130 (E3), .−12448.631 (E6), and .−12809.334 (E9). After optimization, the RMSD value between the optimized structure (the 7BUYoptimized model) and the original structure is 0.004811 Å. We find the HBs JRY401.O-A:Gly143.H, JRY401.O-Cys145.H, DMS405.O-Gln192.H, and DMS405-Thr190.H and other residue-pair HBs: ASP216-ALA211, LEU282-ASP216, ILE213-TYR209, TYR209-ILE259, SER284-ILE281, SER254-LEU250, ARG298-PHE294, LYS269-CYS265, ASP153-CYS156, CYS128-PHE112, VAL114-TYR126, SER113-PHE150, VAL157-LYS100, CYS16-VAL13, LYS97-ASN95, ARG131-ASP289, ILE200ASP289, ASN203-GLY109, SER139-TYR126, ASN95-TRP31, LEU242-ASN231, ASN231-LEU242, GLY109-MET130, GLN107-GLN110, CYS160-GLY149, PHE159-LYS102, GLY29-VAL18, ALA70-VAL73, MET235-ASN231, ARG131THR135, HIS163-TYR161, TYR182-CYS160, VAL104-PHE159, VAL20-LEU27, LEU75-VAL68, ASN133-GLY195, PHE134-ARG131, ALA173-MET165, MET162-THR175, GLY146-HIS163, TYR182-GLY174, LEU89-VAL36, ILE78LYS90, ARG105-PHE181, ASN84-GLU178, VAL86-GLN83, LYS88-SER81, PHE66-ASN63, GLN192-VAL186, CYS85-GLY179, ARG40-ASP187, GLN83VAL86, TYR54-ASP187, THR45-ASP48, SER62-ASN65, ASP48-THR45, and LYS61-LEU58. We also find seven residue-pair SBs, SP187-ARG40, ASP176-ARG105, ASP197-ARG131, ASP229-LYS269, GLU166-HIS172, ASP289-ARG131, and GLU290-ARG131, and five .π -.π stackings HIS163PHE140-HIS172-HIS163, TYR37-PHE103, and TRP218-PHE219. We show the Ramachandran plot and the ligand interaction diagram, respectively, for the 7BUYoptimized model in Fig. 2.5 (comparing it with Figs. 2.1, 2.2, and 2.3) for further studies.
2.3 Results and Discussions
39
Fig. 2.5 The Ramachandran plot and the carmofur-3CLpro interaction diagram for the 7BUYoptimized model
2.3.2 Dimer 2.3.2.1
The 3CLpro (with Unliganded Active Site): The 6Y84-Dimer Model
We optimize the original structure with PDB entry 6Y84 [259], and the optimized structure (the 6Y84optimized model) has an RMSD value of 17.814106 Å from its original structure (20.212018 Å for the dimer). For the 6Y84optimized model, we get its following structural bioinformatics—which will be confirmed with our analysis of the MD data (with data ID DESRES-ANTON-10880334) in [321]. With oxygen-nitrogen cutoff of 3.2 Å, the 6Y84optimized model has the following SBs: ASP187-ARG40, ASP155-LYS100, ASP197-ARG131, ASP295-ARG298, GLU290ARG131, ASP289-ARG131, ASP176-ARG105, ASP229-LYS269, and GLU166-HIS172 in each inner monomer and GLU290-ARG4 between the two monomers. We set 3.0 Å as the donor-acceptor cutoff distance and 20 degrees as the cutoff angle for HBs and find 71 HBs (confirmed in Table 2.4 by the MD) for the 6Y84optimized model. We find four .π -.π stackings PHE103-TYR37, HIS172PHE140-HIS163-HIS172 (with HB HIS163.NE2-HIS172.ND1 (19.28%)), and one + .π -cation PHE291-LYS. 5:NZ. The analysis of 100 .μs’ MD trajectory data in [321] can confirm to us the strong inner-monomer SBs: ◦ ASP187-ARG40 (with strong HBs ARG40.NH2-ASP187.OD1 (70.63%) and ARG40.NE-ASP187.OD2 (69.63%): the SB and HBs are broken during 92.6– 100 .μs),
.
40
2 3C-Like Protease (3CLpro)
◦ ASP295-ARG298 (with HBs ARG298.NH1-ASP295.OD1 (15.38%), ARG298. NH1-ASP295.OD2 (12.99%), ARG298.NH2-ASP295.OD2 (8.29%), and ARG298.NH2-ASP295.OD1 (7.59%)), .◦ ASP176-ARG105 (with strong HBs ARG105.NH1-ASP176.OD1 (32.27%) and ARG105.NH1-ASP176.OD2 (30.77%)), .◦ ASP289-ARG131 (with HBs ARG131.NH2-ASP289.OD2 (26.27%), ARG131. NH2-ASP289.OD1 (23.48%), ARG131.NH1-ASP289.OD1 (12.09%), ARG131. NH1-ASP289.OD2 (9.89%), ARG131.NE-ASP289.OD2 (9.39%), and ARG131.NE-ASP289.OD1 (9.29%)), .◦ GLU290-LYS5 (with strong HBs LYS5.NZ-GLU290.OE2 (54.25%) and LYS5.NZ-GLU290.OE1 (52.95%)), .◦ ASP155-LYS100 (with HBs LYS100.NZ-ASP155.OD1 (15.78%) and LYS100.NZ-ASP155.OD2 (14.69%)) (see Fig. 2.19), and .◦ weaker SBs GLU166-HIS172, GLU290-ARG131 (broken after 2.4 .μs), and ASP229-LYS269 (with strong HB LYS269.NZ-ASP229.O (29.07%)) (Fig. 2.19). .
We discuss the performance of the MD. The RMSD values of the MD equilibrates around 2.5 Å and are within 2 Å of variations (Fig. 2.6).
Fig. 2.6 The RMSF and RMSD for dimeric 3CLpro of the 6Y84optimized model during 100 .μs’ MD
During the 100 .μs’ MD, the secondary structural changes (Fig. 2.20, where the frame interval is 0.1 .μs) are mainly in segments 39–53 of both monomers and segments 222–239 and 298–306 of monomer B; and the large RMSF values mainly happen in residue segments 46–51, 136–141, and 303–306 (Fig. 2.6).
2.3.2.2
The 3CLpro (Without Any Ligand): The 6LU7-Dimer Model
For the file 6LU7.pdb, we remove the C-chain (i.e., inhibitor N3) and just keep the A-chain (3CLpro). Then we apply the following mathematical formula to get a
2.3 Results and Discussions
41
dimer (original structure) with AB-chains of 3CLpro: ⎛
⎞ ⎛ ⎞ −1 0 0 −43.04696 ⎠ .B = ⎝ 0 1 0 ⎠ A + ⎝ 0 0 0 −1 94.23992
(2.1)
and we then optimize this dimer (to get an optimized structure) by the decreased energies (KJ/mol) .−36500.988 (E102), .−37390.438 (E204), and .−37605.098 (E248) with an RMSD value of 1.470148 Å from the original dimer structure. For the optimized model, we get 127 HBs which can be confirmed by the analysis of MD data of [180] in Tables 2.5 and 2.6. For the 6LU7-dimer-optimized model, we get the same SBs as that of the 6Y84-dimer-optimized model : ASP187-ARG40, ASP197-ARG131, GLU290-ARG131, ASP289-ARG131, ASP176-ARG105, GLU166-HIS172, ASP92-ARG76, and GLU290-LYS5 in each inner monomer and GLU290-ARG4 between each monomer. We confirm some strong SBs among them in Figs. 2.21 and 2.22 by the analysis of MD data of [180] in both sets of trajectories. The SB ASP155-LYS100 strongly maintains a pocket of 3CLpro. Now, we analyze the reliability of the MD data of [180]. Seeing Fig. 2.7, we know that the RMSD values for Traj1 steadily go up from 6600 ns to 10000 ns but are stable during 0–6600 ns, but on the contrary for Traj2 during 6600–10000 ns, the RMSD values equilibrate around 3.2 Å, but during 0–6600 ns, the RMSD values go up slowly. The whole variations of RMSD values are within 3 Å and 2 Å, respectively, for the Traj1 and Traj2 sects of MD data.
Fig. 2.7 The RMSD-time (Å-ns) graphs for the 10,000 ns’ MD data of [180] for the 6LU7-dimer model (the left graph is for the Traj1-MD data and the right graph is for the Traj2-MD data)
The RMSF graphs in Fig. 2.8 show that (i) from 6600 ns to 10000 ns, the residue segment 226–286 (even the segment 191–286) seems to unfold or has a large change and (ii) the segments 46–56, 271–276, and 301–306 have large RMSF values.
42
2 3C-Like Protease (3CLpro)
Fig. 2.8 The RMSF graphs for the 10,000 ns’ MD data of [180] for the 6LU7-dimer model (the left graph is for the Traj1-MD data and the right graph is for the Traj2-MD data)
The MD secondary structural developments for Traj1 and Traj2 can be seen from Fig. 2.9. In Fig. 2.9, we know that the segment around residue PRO52 will be changed from .α-helix to turn starting from 1520th ns for B-chain and from 1760th ns for A-chain (in Traj2 for both AB-chains starting from 14th and 32th ns, respectively), the segment around residue LYS137 changes between turn and 3.10 -helix structures, for A-chain the .α-helices in segment 290–306 have unfolded into turns, and for the segment around ARG188, the coils changed into turns during Traj2 6940-10000 ns for A-chain. However, we cannot see significant changes of secondary structures of the monomer (Fig. 2.18)—this may be explained by the longer 10,000 ns’ MD here but the MD of the 6LU7-monomer is 100 ns in all.
Fig. 2.9 The secondary structural graphs for the 10,000 ns’ MD data of [180] for the 6LU7-dimer model (the left graph is for the Traj1-MD data and the right graph is for the Traj2-MD data; the frame interval is 10 ns).
For the optimized Evans-dimer model, we find 6 .π -interactions, A:ARG298. NH2+-A:PHE8-A:PHE305, B:ARG298.NH2+-B:PHE8-B:PHE305, A:PHE134A:ARG105.NH2+, and B:PHE134-B:ARG105.NH2+, and 32 SBs (Fig. 2.23): − in rep0: • A:GLU290-B:ARG4/B:GLU290-A:ARG4 (with HBs B:ARG4.NH1-A:GLU 290.OE2 37.56%, B:ARG4.NH2-A:GLU290.OE1 31.77%, B:ARG4.NH1A:GLU290.OE1 24.58%, B:ARG4.NH2-A:GLU290.OE2 19.48%/A:ARG4. NH1-B:GLU290.OE2 33.67%, A:ARG4.NH2-B:GLU290.OE1 22.68%, A:ARG4.NH1-B:GLU290.OE1 14.29%),
.
2.3 Results and Discussions
43
• A:ASP34-A:LYS90/B:ASP34-B:LYS90 (with HBs A:LYS90.NZ-A:ASP34.OD1 27.17%, A:LYS90.NZ-A:ASP34.OD2 21.68%, A:LYS90.N-A:GLY79.O 52.15%, A:ILE78.N-A:LYS90.O 51.95%, A:VAL91.N-A:ASP34.O 47.65%/B: LYS90.NZ-B:ASP34.OD1 27.77%, B:LYS90.NZ-B:ASP34.OD2 22.88%, B:VAL91.N-B:ASP34.O 42.16%, B:LYS90.N-B:GLY79.O 52.45%, B:ILE78.NB:LYS90.O 49.45%), • A:ASP48-A:ARG60/B:ASP48-B:ARG60 (with HBs A:ARG60.NH1-A:ASP4 8.OD1 20.28%, A:ARG60.NH2-A:ASP48.OD2 18.08%, A:THR45.OG1A:ASP48.OD1 27.77%, A:THR45.OG1-A:ASP48.OD2 24.88%, A:THR45.NA:ASP48.OD2 16.68%, A:THR45.N-A:ASP48.OD1 15.68%/B:ARG60.NH1B:ASP48.OD2 10.09%, B:THR45.OG1-B:ASP48.OD2 27.87%, B:THR45.NB:ASP48.OD2 19.18%, B:THR45.OG1-B:ASP48.OD1 18.78%, B:THR45.NB:ASP48.OD1 10.69%, B:ARG60.NH1-B:ASP56.OD2 11.19%), • A:ASP92-A:ARG76/B:ASP92-B:ARG76 (with HBs A:ARG76.NE-A:ASP92. OD1 17.08%, A:ARG76.NH2-A:ASP92.OD1 14.09%, A:ASP92.N-A:ARG76.O 12.19%, A:ARG76.NH2-A:ASP92.OD2 11.99%, A:ARG76.NE-A:ASP92.OD2 10.49%, A:THR93.OG1-A:ASP92.OD2 25.77%/B:ARG76.NE-B:ASP92.OD2 18.88%, B:ARG76.NH2-B:ASP92.OD1 14.89%, B:ARG76.NH2-B:ASP92. OD2 13.59%, B:ARG76.NE-B:ASP92.OD1 13.39%, B:THR93.OG1-B:ASP92. OD1 17.48%, B:THR93.OG1-B:ASP92.OD2 16.58%), • A:ASP153-A:LYS102/B:ASP153-B:LYS102 (with HBs A:LYS102.NZA:ASP153.OD2 15.88%, A:LYS102.NZ-A:ASP153.OD1 14.49%, A:ASP153. N-A:CYS156.O 45.25%, A:CYS156.N-A:ASP153.O 28.67%, A:PHE159.NA:LYS102.O 30.17%, A:LYS102.N-A:VAL157.O 10.09%/ B:LYS102.NZB:ASP153.OD2 21.08%, B:ASP153.N-B:CYS156.O 44.06%, B:CYS156.NB:ASP153.O 33.27%, B:PHE159.N-B:LYS102.O 30.87%), • A:ASP155-A:LYS100/B:ASP155-B:LYS100 (with HBs A:LYS100.NZA:ASP155.OD2 40.36%, A:VAL157.N-A:LYS100.O 49.85%/B:LYS100.NZB:ASP155.OD2 39.06%, B:VAL157.N-B:LYS100.O 47.15%), • A:ASP176-A:ARG105/B:ASP176-B:ARG105 (with HBs A:ARG105.NH1A:ASP176.OD2 44.46%, A:ARG105.NH1-A:ASP176.OD1 13.99%, A:ASN 180.N-A:ASP176.OD1 53.85%, A:ASN180.N-A:ASP176.OD2 17.28%, A:ASP 176. N-A:ASN180.O 13.59%, A:THR175.OG1-A:ASP176.O 33.37%, A:ARG 105.NH2-A:PHE181.O 56.74%/B:ARG105.NH1-B:ASP176.OD2 28.77%, B:ARG105.NH1-B:ASP176.OD1 28.47%, B:ASN180.N-B:ASP176.OD1 34.87%, B:ASN180.N-B:ASP176.OD2 34.57%, B:ASP176.N-B:ASN180.O 16.48%, B:THR175.OG1-B:ASP176.O 33.87%, B:ARG105.NH2-B:PHE181.O 52.65%, B:ARG105.NH1-B:ASN180.O 10.09%), • A:ASP187-A:ARG40/B:ASP187-B:ARG40 (with HBs A:ARG40.NE-A:ASP 187.OD2 79.12%, A:ARG40.NH2-A:ASP187.OD1 58.84%, A:TYR54.OHA:ASP187.OD1 27.87%, A:TYR54.OH-A:ASP187.OD2 12.49%/B:ARG40. NE-B:ASP187.OD2 68.23%, B:ARG40.NH2-B:ASP187.OD1 51.65%, B:TYR5 4.OH-B:ASP187.OD2 15.28%, B:TYR54.OH-B:ASP187.OD1 14.59%), • A:ASP197-A:ARG131/B:ASP197-B:ARG131 (with HBs A:ARG131.NEA:ASP197.OD1 23.68%, A:ARG131.NE-A:ASP197.OD2 15.68%, A:LYS137.
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2 3C-Like Protease (3CLpro)
NZ-A:ASP197.OD2 12.89%, A:ARG131.NH2-A:ASP289.OD2 46.45%, A:ARG131.NH1-A:ASP289.OD1 31.27%, A:ARG131.NH1-A:ASP289.OD2 14.59%, A:ARG131.N-A:THR135.O 32.17%, A:PHE134.N-A:ARG131.O 13.49%/B:ARG131.NE-B:ASP197.OD2 20.38%, B:ARG131.NE-B:ASP197. OD1 15.28%, B:LYS137.NZ-B:ASP197.OD1 12.19%, B:ARG131.NH2B:ASP289.OD2 55.84%, B:ARG131.NH1-B:ASP289.OD1 33.77%, B:ARG131. NH1-B:ASP289.OD2 11.09%, B:ARG131.N-B:THR135.O 31.57%, B:PHE134. N-B:ARG131.O 12.79%), A:ASP197-A:LYS137/B:ASP197-B:LYS137 (with HBs A:LYS137.NZ-A:ASP 197.OD2 12.89%, A:ARG131.NE-A:ASP197.OD1 23.68%, A:ARG131.NEA:ASP197.OD2 15.68%/B:ARG131.NE-B:ASP197.OD2 20.38%, B:ARG131. NE-B:ASP197.OD1 15.28%, B:LYS137.NZ-B:ASP197.OD1 12.19%, B:TYR 126.OH-B:LYS137.O 17.18%), A:ASP229-A:LYS269/B:ASP229-B:LYS269 (weak during MD; with HBs A:THR226.OG1-A:ASP229.OD1 10.29%, A:LYS269.N-A:CYS265.O 36.56%, A:GLN273.N-A:LYS269.O 25.17%, A:LYS269.NZ-A:GLU270.OE2 14.69%, A:LYS269.NZ-A:GLU270.OE1 12.69%/B:LYS269.N-B:CYS265.O 40.26%, B:GLN273.N-B:LYS269.O 24.38%, B:LYS269.NZ-B:GLU270.OE1 17.98%), A:ASP289-A:ARG131/B:ASP289-B:ARG131 (with HBs A:ARG131.NH2A:ASP289.OD2 46.45%, A:ARG131.NH1-A:ASP289.OD1 31.27%, A:ARG 131.NH1-A:ASP289.OD2 14.59%, A:ASN203.ND2-A:ASP289.O 36.46%, A:ILE200.N-A:ASP289.OD2 35.86%, A:ARG131.N-A:THR135.O 32.17%, A:ARG131.NE-A:ASP197.OD1 23.68%, A:ARG131.NE-A:ASP197.OD2 15.68%, A:PHE134.N-A:ARG131.O 13.49%/B:ARG131.NH2-B:ASP289.OD2 55.84%, B:ARG131.NH1-B:ASP289.OD1 33.77%, B:ARG131.NH1-B:ASP 289.OD2 11.09%, B:ILE200.N-B:ASP289.OD2 45.75%, B:ASN203.ND2B:ASP289.O 36.06%, B:ARG131.N-B:THR135.O 31.57%, B:ARG131.NEB:ASP197.OD2 20.38%, B:ARG131.NE-B:ASP197.OD1 15.28%, B:PHE134. N-B:ARG131.O 12.79%), A:ASP295-A:ARG298/B:ASP295-B:ARG298 (with HBs A:ARG298.NH2A:ASP295.OD1 41.36%, A:ARG298.NH2-A:ASP295.OD2 15.78%, A:THR 111.OG1-A:ASP295.OD2 41.66%, A:THR111.OG1-A:ASP295.OD1 15.98%, A:THR292.N-A:ASP295.OD2 40.26%, A:THR292.OG1-A:ASP295.OD2 31.87%, A:THR292.N-A:ASP295.OD1 15.18%, A:THR292.OG1-A:ASP295. OD1 14.39%, A:GLN299.N-A:ASP295.O 28.57%, A:ARG298.N-A:PHE294.O 53.75%, A:VAL303.N-A:ARG298.O 11.19%/B:ARG298.NH2-B:ASP295.OD1 40.76%, B:ARG298.NH2-B:ASP295.OD2 16.98%, B:THR111.OG1-B:ASP 295.OD2 47.05%, B:THR111.OG1-B:ASP295.OD1 17.98%, B:GLN299.NB:ASP295.O 39.76%, B:THR292.N-B:ASP295.OD2 39.06%, B:THR292.OG1B:ASP295.OD2 31.87%, B:THR292.N-B:ASP295.OD1 15.88%, B:ARG298.NB:PHE294.O 50.75%, B:ARG298.NH1-B:MET6.O 16.08%), A:GLU55-A:ARG40/B:GLU55-B:ARG40 (not existing during MD; with HBs A:ARG40.NE-A:ASP187.OD2 79.12%, A:ARG40.NH2-A:ASP187.OD1 58.84%/B:ARG40.NE-B:ASP187.OD2 68.23%, B:ARG40.NH2-B:ASP187. OD1 51.65%),
2.3 Results and Discussions
45
• A:GLU288-A:LYS5/B:GLU288-B:LYS5 (with HBs A:LYS5.NZ-A:GLU288. OE2 30.17%, A:LYS5.NZ-A:GLU288.OE1 29.37%, A:LYS5.NZ-A:GLU290. OE1 46.55%, A:LYS5.NZ-A:GLU290.OE2 13.89%/B:LYS5.NZ-B:GLU288. OE2 30.77%, B:LYS5.NZ-B:GLU288.OE1 28.17%, B:LYS5.NZ-B:GLU290. OE1 32.97%, B:LYS5.NZ-B:GLU290.OE2 32.17%), • A:GLU290-A:LYS5/B:GLU290-B:LYS5 (with HBs A:LYS5.NZ-A:GLU290. OE1 46.55%, A:LYS5.NZ-A:GLU290.OE2 13.89%, A:LYS5.NZ-A:GLU288. OE2 30.17%, A:LYS5.NZ-A:GLU288.OE1 29.37%/B:LYS5.NZ-B:GLU290. OE1 32.97%, B:LYS5.NZ-B:GLU290.OE2 32.17%, B:LYS5.NZ-B:GLU288. OE2 30.77%, B:LYS5.NZ-B:GLU288.OE1 28.17%); .− in rep1: • A:GLU290-B:ARG4/B:GLU290-A:ARG4 (with HBs B:ARG4.NH1-A:GLU 290.OE2 39.56%, B:ARG4.NH2-A:GLU290.OE1 32.77%, B:ARG4.NH1A:GLU290.OE1 22.08%, B:ARG4.NH2-A:GLU290.OE2 19.28%/A:ARG4. NH1-B:GLU290.OE2 33.87%, A:ARG4.NH2-B:GLU290.OE1 21.58%, A:ARG4.NH1-B:GLU290.OE1 14.99%, A:ARG4.NH2-B:GLU290.OE2 10.69%), • A:ASP34-A:LYS90/B:ASP34-B:LYS90 (with HBs A:LYS90.NZ-A:ASP34.OD1 26.77%, A:LYS90.NZ-A:ASP34.OD2 21.48%, A:VAL91.N-A:ASP34.O 44.06%, A:ILE78.N-A:LYS90.O 50.65%, A:LYS90.N-A:GLY79.O 50.45%/B: LYS90.NZ-B:ASP34.OD1 25.87%, B:LYS90.NZ-B:ASP34.OD2 20.88%, B:VAL91.N-B:ASP34.O 40.26%, B:ILE78.N-B:LYS90.O 53.15%, B:LYS90.NB:GLY79.O 52.75%), • A:ASP48-A:ARG60/B:ASP48-B:ARG60 (with HBs A:ARG60.NH1-A:ASP48. OD1 15.48%, A:ARG60.NH2-A:ASP48.OD2 12.09%, A:THR45.OG1A:ASP48.OD2 30.07%, A:THR45.OG1-A:ASP48.OD1 20.78%, A:THR45.NA:ASP48.OD2 17.68%, A:THR45.N-A:ASP48.OD1 12.09%/B:THR45.OG1B:ASP48.OD2 28.67%, B:THR45.N-B:ASP48.OD2 18.68%, B:THR45.OG1B:ASP48.OD1 16.18%), • A:ASP92-A:ARG76/B:ASP92-B:ARG76 (with HBs A:ARG76.NE-A:ASP92. OD1 15.48%, A:ARG76.NH2-A:ASP92.OD1 12.19%, A:ASP92.N-A:ARG76.O 11.49%, A:ARG76.NH2-A:ASP92.OD2 10.69%, A:ARG76.NE-A:ASP92.OD2 10.19%, A:THR93.OG1-A:ASP92.OD2 22.18%, A:THR93.OG1-A:ASP92.OD1 11.09%/B:ARG76.NE-B:ASP92.OD2 15.98%, B:ARG76.NH2-B:ASP92.OD2 15.48%, B:ARG76.NE-B:ASP92.OD1 13.99%, B:ARG76.NH2-B:ASP92.OD1 12.69%, B:THR93.OG1-B:ASP92.OD1 17.08%, B:THR93.OG1-B:ASP92.OD2 15.58%), • A:ASP153-A:LYS102/B:ASP153-B:LYS102 (with HBs A:LYS102.NZA:ASP153.OD1 17.48%, A:LYS102.NZ-A:ASP153.OD2 15.78%, A:LYS102.NA:VAL157.O 11.29%, A:PHE159.N-A:LYS102.O 28.07%, A:ASP153.NA:CYS156.O 41.86%, A:CYS156.N-A:ASP153.O 27.37%/B:LYS102.NZB:ASP153.OD2 17.98%, B:ASP153.N-B:CYS156.O 44.16%, B:CYS156.NB:ASP153.O 28.87%, B:PHE159.N-B:LYS102.O 28.67%), • A:ASP155-A:LYS100/B:ASP155-B:LYS100 (with HBs A:LYS100.NZA:ASP155.OD2 35.66%, A:VAL157.N-A:LYS100.O 54.05%/B:LYS100.NZ-
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2 3C-Like Protease (3CLpro)
B:ASP155.OD2 37.76%, B:LYS100.NZ-B:ASP155.OD1 10.89%, B:VAL157.NB:LYS100.O 49.95%), A:ASP176-A:ARG105/B:ASP176-B:ARG105 (with HBs A:ARG105.NH1A:ASP176.OD2 44.06%, A:ARG105.NH1-A:ASP176.OD1 14.59%, A:ASN 180.N-A:ASP176.OD1 52.15%, A:ASN180.N-A:ASP176.OD2 19.68%, A:ASP 176.N-A:ASN180.O 14.19% A:THR175.OG1-A:ASP176.O 33.87%, A:ARG 105.NH2-A:PHE181.O 54.15%, A:ARG105.NH1-A:ASN180.O 10.39%/B: ARG105.NH1-B:ASP176.OD2 28.97%, B:ARG105.NH1-B:ASP176.OD1 25.97%, B:ASN180.N-B:ASP176.OD1 37.66%, B:ASN180.N-B:ASP176.OD2 32.17%, B:ASP176.N-B:ASN180.O 15.38%, B:THR175.OG1-B:ASP176.O 32.87%, B:ARG105.NH2-B:PHE181.O 55.24%), A:ASP187-A:ARG40/B:ASP187-B:ARG40 (with HBs A:ARG40.NE-A:ASP 187.OD2 77.32%, A:ARG40.NH2-A:ASP187.OD1 58.54%, A:TYR54.OHA:ASP187.OD1 25.37%, A:TYR54.OH-A:ASP187.OD2 16.18%/B:ARG40. NE-B:ASP187.OD2 65.23%, B:ARG40.NH2-B:ASP187.OD1 55.54%, B:TYR54.OH-B:ASP187.OD1 14.39%, B:TYR54.OH-B:ASP187.OD2 13.79%, B:TYR182.OH-B:CYS160.O 65.33%), A:ASP197-A:ARG131/B:ASP197-B:ARG131 (with HBs A:ARG131.NEA:ASP197.OD1 21.38%, A:ARG131.NE-A:ASP197.OD2 16.68%, A:LYS137. NZ-A:ASP197.OD2 13.89%, A:ARG131.NH2-A:ASP289.OD2 51.85%, A:ARG131.NH1-A:ASP289.OD1 36.96%, A:ARG131.NH1-A:ASP289.OD2 12.69%, A:ARG131.N-A:THR135.O 31.97%, A:PHE134.N-A:ARG131.O 11.79%/B:ARG131.NE-B:ASP197.OD2 18.98%, B:ARG131.NE-B:ASP197. OD1 16.18%, B:LYS137.NZ-B:ASP197.OD1 12.89%, B:ARG131.NH2B:ASP289.OD2 58.24%, B:ARG131.NH1-B:ASP289.OD1 39.46%, B:ARG 131.N-B:THR135.O 32.37%, B:PHE134.N-B:ARG131.O 12.49%), A:ASP197-A:LYS137/B:ASP197-B:LYS137 (with HBs A:LYS137.NZA:ASP197.OD2 13.89%, A:ARG131.NE-A:ASP197.OD1 21.38%, A:ARG131. NE-A:ASP197.OD2 16.68%/B:LYS137.NZ-B:ASP197.OD1 12.89%, B:ARG 131.NE-B:ASP197.OD2 18.98%, B:ARG131.NE-B:ASP197.OD1 16.18%, B:TYR126.OH-B:LYS137.O 16.78%), A:ASP229-A:LYS269/B:ASP229-B:LYS269 (weak during MD; with HBs A:LYS269.N-A:CYS265.O 33.77%, A:GLN273.N-A:LYS269.O 27.57%, A:LYS269.NZ-A:GLU270.OE1 13.79%, A:LYS269.NZ-A:GLU270.OE2 13.49%/B:LYS269.N-B:CYS265.O 40.26%, B:GLN273.N-B:LYS269.O 22.38%, B:LYS269.NZ-B:GLU270.OE1 18.78%), A:ASP289-A:ARG131/B:ASP289-B:ARG131 (with HBs A:ARG131.NH2A:ASP289.OD2 51.85%, A:ARG131.NH1-A:ASP289.OD1 36.96%, A:ARG 131.NH1-A:ASP289.OD2 12.69%, A:ILE200.N-A:ASP289.OD2 36.06%, A:ASN203.ND2-A:ASP289.O 35.96%, A:ARG131.N-A:THR135.O 31.97%, A:PHE134.N-A:ARG131.O 11.79%, A:ARG131.NE-A:ASP197.OD1 21.38%, A:ARG131.NE-A:ASP197.OD2 16.68%/B:ARG131.NH2-B:ASP289.OD2 58.24%, B:ARG131.NH1-B:ASP289.OD1 39.46%, B:ILE200.N-B:ASP289. OD2 46.45%, B:ASN203.ND2-B:ASP289.O 37.46%, B:ARG131.N-B:THR
2.3 Results and Discussions
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135.O 32.37%, B:ARG131.NE-B:ASP197.OD2 18.98%, B:ARG131.NEB:ASP197.OD1 16.18%, B:PHE134.N-B:ARG131.O 12.49%), A:ASP295-A:ARG298/B:ASP295-B:ARG298 (with HBs A:ARG298.NH2A:ASP295.OD1 42.66%, A:ARG298.NH2-A:ASP295.OD2 14.79%, A:THR 111.OG1-A:ASP295.OD2 43.76%, A:THR111.OG1-A:ASP295.OD1 14.39%, A:THR292.N-A:ASP295.OD2 37.06%, A:THR292.OG1-A:ASP295.OD2 32.07%, A:THR292.N-A:ASP295.OD1 13.59%, A:THR292.OG1-A:ASP295. OD1 12.69%, A:GLN299.N-A:ASP295.O 27.37%, A:ARG298.N-A:PHE294.O 49.25%, A:VAL303.N-A:ARG298.O 13.69%/B:ARG298.NH2-B:ASP295.OD1 39.76%, B:ARG298.NH2-B:ASP295.OD2 13.69%, B:THR111.OG1-B:ASP 295.OD2 50.85%, B:THR111.OG1-B:ASP295.OD1 13.69%, B:THR292.NB:ASP295.OD2 39.46%, B:THR292.OG1-B:ASP295.OD2 30.97%, B:THR292. N-B:ASP295.OD1 13.29%, B:GLN299.N-B:ASP295.O 35.46%, B:ARG298.NB:PHE294.O 52.75%, B:ARG298.NH1-B:MET6.O 13.99%), A:GLU55-A:ARG40/B:GLU55-B:ARG40 (not existing during MD; with HBs A:ARG40.NE-A:ASP187.OD2 77.32%, A:ARG40.NH2-A:ASP187.OD1 58.54%/B:ARG40.NE-B:ASP187.OD2 65.23%, B:ARG40.NH2-B:ASP187. OD1 55.54%), A:GLU288-A:LYS5/B:GLU288-B:LYS5 (with HBs A:LYS5.NZ-A:GLU288. OE1 29.37%, A:LYS5.NZ-A:GLU288.OE2 28.37%, A:LYS5.NZ-A:GLU290. OE1 44.26%, A:LYS5.NZ-A:GLU290.OE2 14.69%/B:LYS5.NZ-B:GLU288. OE1 27.97%, B:LYS5.NZ-B:GLU288.OE2 25.77%, B:LYS5.NZ-B:GLU290. OE1 31.37%, B:LYS5.NZ-B:GLU290.OE2 29.27%), A:GLU290-A:LYS5/B:GLU290-B:LYS5 (with HBs A:LYS5.NZ-A:GLU290. OE1 44.26%, A:LYS5.NZ-A:GLU290.OE2 14.69%, A:LYS5.NZ-A:GLU288. OE1 29.37%, A:LYS5.NZ-A:GLU288.OE2 28.37%/B:LYS5.NZ-B:GLU290. OE1 31.37%, B:LYS5.NZ-B:GLU290.OE2 29.27%, B:LYS5.NZ-B:GLU288. OE1 27.97%, B:LYS5.NZ-B:GLU288.OE2 25.77%); in rep2: A:GLU290-B:ARG4/B:GLU290-A:ARG4 (with HBs B:ARG4.NH1-A:GLU 290.OE2 38.76%, B:ARG4.NH2-A:GLU290.OE1 30.17%, B:ARG4.NH1A:GLU290.OE1 20.68%, B:ARG4.NH2-A:GLU290.OE2 19.28%/A:ARG4. NH1-B:GLU290.OE2 36.06%, A:ARG4.NH2-B:GLU290.OE1 23.78%, A:ARG4.NH1-B:GLU290.OE1 13.99%, A:ARG4.NH2-B:GLU290.OE2 10.69%), A:ASP34-A:LYS90/B:ASP34-B:LYS90 (with HBs A:LYS90.NZ-A:ASP34.OD1 27.17%, A:LYS90.NZ-A:ASP34.OD2 19.58%, A:VAL91.N-A:ASP34.O 40.76%, A:LYS90.N-A:GLY79.O 50.45%, A:ILE78.N-A:LYS90.O 49.35%/B: LYS90.NZ-B:ASP34.OD1 26.17%, B:LYS90.NZ-B:ASP34.OD2 20.88%, B:VAL91.N-B:ASP34.O 40.36%, B:LYS90.N-B:GLY79.O 47.65%, B:ILE78.NB:LYS90.O 53.85%), A:ASP48-A:ARG60/B:ASP48-B:ARG60 (with HBs A:ARG60.NH2-A:ASP48. OD2 10.29%, A:ARG60.NH1-A:ASP48.OD1 10.19%, A:THR45.OG1A:ASP48.OD2 32.37%, A:THR45.OG1-A:ASP48.OD1 20.28%, A:THR45.NA:ASP48.OD2 20.08%, A:THR45.N-A:ASP48.OD1 11.39%/B:THR45.OG1-
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2 3C-Like Protease (3CLpro)
B:ASP48.OD2 25.17%, B:THR45.N-B:ASP48.OD2 16.88%, B:THR45.OG1B:ASP48.OD1 14.79%), A:ASP92-A:ARG76/B:ASP92-B:ARG76 (with HBs A:ASP92.N-A:ARG76.O 13.69%, A:ARG76.NH2-A:ASP92.OD1 12.79%, A:ARG76.NE-A:ASP92.OD2 12.69%, A:ARG76.NE-A:ASP92.OD1 10.69%, A:THR93.OG1-A:ASP92.OD2 18.28%, A:THR93.OG1-A:ASP92.OD1 14.29%/B:ARG76.NE-B:ASP92.OD2 17.28%, B:ARG76.NH2-B:ASP92.OD2 15.38%, B:ARG76.NH2-B:ASP92.OD1 14.39%, B:ARG76.NE-B:ASP92.OD1 12.99%, B:THR93.OG1-B:ASP92.OD1 15.68%), A:ASP153-A:LYS102/B:ASP153-B:LYS102 (with HBs A:LYS102.NZA:ASP153.OD1 15.08%, A:LYS102.NZ-A:ASP153.OD2 13.99%, A:ASP153. N-A:CYS156.O 46.15%, A:CYS156.N-A:ASP153.O 28.67%, A:PHE159.NA:LYS102.O 32.17%, A:LYS102.N-A:VAL157.O 10.99%/B:LYS102.NZB:ASP153.OD2 18.58%, B:LYS102.NZ-B:ASP153.OD1 10.09%, B:ASP153.NB:CYS156.O 44.06%, B:CYS156.N-B:ASP153.O 28.27%, B:PHE159.NB:LYS102.O 29.77%), A:ASP155-A:LYS100/B:ASP155-B:LYS100 (with HBs A:LYS100.NZA:ASP155.OD2 32.37%, A:LYS100.NZ-A:ASP155.OD1 11.19%, A:VAL157. N-A:LYS100.O 49.25%/B:LYS100.NZ-B:ASP155.OD2 37.56%, B:LYS100. NZ-B:ASP155.OD1 11.49%, B:VAL157.N-B:LYS100.O 49.25%), A:ASP176-A:ARG105/B:ASP176-B:ARG105 (with HBs A:ARG105.NH1A:ASP176.OD2 38.26%, A:ARG105.NH1-A:ASP176.OD1 18.78%, A:ASN 180.N-A:ASP176.OD1 47.05%, A:ASN180.N-A:ASP176.OD2 24.08%, A:ASP176.N-A:ASN180.O 12.79%, A:THR175.OG1-A:ASP176.O 32.37%, A:ARG105.NH2-A:PHE181.O 56.24%/B:ARG105.NH1-B:ASP176.OD2 30.67%, B:ARG105.NH1-B:ASP176.OD1 27.27%, B:ASN180.N-B:ASP176. OD2 36.56%, B:ASN180.N-B:ASP176.OD1 36.36%, B:ASP176.N-B:ASN 180.O 17.68%, B:THR175.OG1-B:ASP176.O 31.37%, B:ARG105.NH2B:PHE181.O 53.35%), A:ASP187-A:ARG40/B:ASP187-B:ARG40 (with HBs A:ARG40.NE-A:ASP 187.OD2 73.63%, A:ARG40.NH2-A:ASP187.OD1 52.45%, A:TYR54.OHA:ASP187.OD1 25.37%, A:TYR54.OH-A:ASP187.OD2 13.79%/B:ARG40. NE-B:ASP187.OD2 68.33%, B:ARG40.NH2-B:ASP187.OD1 54.25%, B:TYR 54.OH-B:ASP187.OD1 13.69%, B:TYR54.OH-B:ASP187.OD2 12.09%), A:ASP197-A:ARG131/B:ASP197-B:ARG131 (with HBs A:ARG131.NEA:ASP197.OD1 20.28%, A:ARG131.NE-A:ASP197.OD2 17.78%, A:LYS137. NZ-A:ASP197.OD2 12.79%, A:ARG131.NH2-A:ASP289.OD2 52.15%, A:ARG131.NH1-A:ASP289.OD1 36.46%, A:ARG131.N-A:THR135.O 33.57%, A:PHE134.N-A:ARG131.O 13.19%/B:ARG131.NE-B:ASP197.OD2 18.28%, B:ARG131.NE-B:ASP197.OD1 15.88%, B:LYS137.NZ-B:ASP197. OD1 12.79%, B:ARG131.NH2-B:ASP289.OD2 57.04%, B:ARG131.NH1B:ASP289.OD1 36.36%, B:ARG131.N-B:THR135.O 31.17%, B:PHE134.NB:ARG131.O 12.69%), A:ASP197-A:LYS137/B:ASP197-B:LYS137 (with HBs A:LYS137.NZA:ASP197.OD2 12.79%, A:ARG131.NE-A:ASP197.OD1 20.28%, A:ARG131.
2.3 Results and Discussions
•
•
•
•
•
•
49
NE-A:ASP197.OD2 17.78%/B:LYS137.NZ-B:ASP197.OD1 12.79%, B:ARG 131.NE-B:ASP197.OD2 18.28%, B:ARG131.NE-B:ASP197.OD1 15.88%, B:TYR126.OH-B:LYS137.O 16.08%), A:ASP229-A:LYS269/B:ASP229-B:LYS269 (weak during MD; with HBs A:LYS269.N-A:CYS265.O 34.67%, A:GLN273.N-A:LYS269.O 23.48%, A:LYS269.NZ-A:GLU270.OE2 11.79%, A:LYS269.NZ-A:GLU270.OE1 10.39%/B:LYS269.N-B:CYS265.O 35.06%, B:GLN273.N-B:LYS269.O 21.78%, B:LYS269.NZ-B:GLU270.OE1 16.98%), A:ASP289-A:ARG131/B:ASP289-B:ARG131 (with HBs A:ARG131.NH2A:ASP289.OD2 52.15%, A:ARG131.NH1-A:ASP289.OD1 36.46%, A:ASN 203.ND2-A:ASP289.O 36.26%, A:ILE200.N-A:ASP289.OD2 35.76%, A:ARG131.N-A:THR135.O 33.57%, A:PHE134.N-A:ARG131.O 13.19%, A:ARG131.NE-A:ASP197.OD1 20.28%, A:ARG131.NE-A:ASP197.OD2 17.78%/B:ARG131.NH2-B:ASP289.OD2 57.04%, B:ARG131.NH1-B:ASP 289.OD1 36.36%, B:ILE200.N-B:ASP289.OD2 40.96%, B:ASN203.ND2B:ASP289.O 36.66%, B:ARG131.N-B:THR135.O 31.17%, B:PHE134.NB:ARG131.O 12.69%, B:ARG131.NE-B:ASP197.OD2 18.28%, B:ARG131. NE-B:ASP197.OD1 15.88%), A:ASP295-A:ARG298/B:ASP295-B:ARG298 (with HBs A:ARG298.NH2A:ASP295.OD1 39.86%, A:ARG298.NH2-A:ASP295.OD2 14.89%, A:THR 111.OG1-A:ASP295.OD2 41.46%, A:THR111.OG1-A:ASP295.OD1 18.08%, A:THR292.N-A:ASP295.OD2 38.76%, A:THR292.OG1-A:ASP295.OD2 31.07%, A:THR292.N-A:ASP295.OD1 16.68%, A:THR292.OG1-A:ASP295. OD1 12.19%, A:GLN299.N-A:ASP295.O 29.17%, A:ARG298.N-A:PHE294.O 48.05%, A:VAL303.N-A:ARG298.O 12.29%/B:ARG298.NH2-B:ASP295.OD1 39.36%, B:ARG298.NH2-B:ASP295.OD2 12.39%, B:THR292.OG1-B:ASP 295.OD2 30.77%, B:THR111.OG1-B:ASP295.OD2 47.25%, B:THR111.OG1B:ASP295.OD1 14.99%, B:THR292.N-B:ASP295.OD2 38.26%, B:THR292.NB:ASP295.OD1 12.19%, B:GLN299.N-B:ASP295.O 33.27%, B:ARG298.NB:PHE294.O 49.75%, B:ARG298.NH1-B:MET6.O 15.48%), A:GLU55-A:ARG40/B:GLU55-B:ARG40 (not existing during MD; with HBs A:ARG40.NE-A:ASP187.OD2 73.63%, A:ARG40.NH2-A:ASP187.OD1 52.45%/B:ARG40.NE-B:ASP187.OD2 68.33%, B:ARG40.NH2-B:ASP187. OD1 54.25%), A:GLU288-A:LYS5/B:GLU288-B:LYS5 (with HBs A:LYS5.NZ-A:GLU288. OE2 29.37%, A:LYS5.NZ-A:GLU288.OE1 28.07%, A:LYS5.NZ-A:GLU290. OE1 43.96%, A:LYS5.NZ-A:GLU290.OE2 14.49%/B:LYS5.NZ-B:GLU288. OE1 26.17%, B:LYS5.NZ-B:GLU288.OE2 24.68%, B:LYS5.NZ-B:GLU290. OE1 36.46%, B:LYS5.NZ-B:GLU290.OE2 25.17%), A:GLU290-A:LYS5/B:GLU290-B:LYS5 (with HBs A:LYS5.NZ-A:GLU290. OE1 43.96%, A:LYS5.NZ-A:GLU290.OE2 14.49%, A:LYS5.NZ-A:GLU288. OE2 29.37%, A:LYS5.NZ-A:GLU288.OE1 28.07%/B:LYS5.NZ-B:GLU290. OE1 36.46%, B:LYS5.NZ-B:GLU290.OE2 25.17%, B:LYS5.NZ-B:GLU288. OE1 26.17%, B:LYS5.NZ-B:GLU288.OE2 24.68%);
50
2 3C-Like Protease (3CLpro)
where in each monomer, the polar contacts ASP34-LYS90, ASP48-ARG60, ASP92ARG76, ASP153-LYS102, ASP155-LYS100, ASP176-ARG105, ASP187-ARG40, ASP197-ARG131, ASP197-LYS137, ASP289-ARG131, ASP295-ARG298, GLU288-LYS5, and GLU290-LYS5 are strong and stable during the three sets of REMDs: rep0, rep1, and rep2. Table 2.7 lists the HBs with more than 50% occupancy rates during the three sets of 50 .μs’ REMD rep0-rep1-rep3 for the Evans-dimer model, where the HBs linking the two monomers (A-chain and B-chain) are the following: − 1. 2. 3.
.
4. 5. 6. 7.
8. 9. 10. .− 11. 12.
13. 14. 15. 16. 17.
in rep0: A:SER123.OG-B:VAL303.O 53.65%/B:SER123.OG-A:VAL303.O 53.35%, A:PHE305.N-B:PRO122.O 38.16%/B:PHE305.N-A:PRO122.O 31.27%, A:ARG4.NH1-B:GLU290.OE2 33.67%, A:ARG4.NH2-B:GLU290.OE1 22.68%, A:ARG4.NH1-B:GLU290.OE1 14.29%/B:ARG4.NH1-A:GLU290. OE2 37.56%, B:ARG4.NH2-A:GLU290.OE1 31.77%, B:ARG4.NH1-A:GLU 290.OE1 24.58%, B:ARG4.NH2-A:GLU290.OE2 19.48%, A:PHE140.N-B:SER1.O 29.57%/B:PHE140.N-A:SER1.O 17.58%, A:ALA7.N-B:VAL125.O 29.17%, B:VAL125.N-A:ALA7.O 20.58%/B:ALA7. N-A:VAL125.O 23.68%, A:GLY11.N-B:GLU14.OE2 22.78%/B:GLY11.N-A:GLU14.OE2 18.48%, A:SER1.N-B:GLU166.OE2 18.38%, A:SER1.N-B:GLU166.OE1 18.18%, A:SER1.OG-B:GLU166.OE2 10.49%, A:SER1.N-B:HSD172.NE2 17.18%, A:SER1.N-B:PHE140.O 12.59%/B:SER1.N-A:GLU166.OE2 24.68%, B:SER1.N-A:GLU166.OE1 22.18%, B:SER1.OG-A:GLU166.OE2 14.39%, B:SER1.OG-A:GLU166.OE1 10.79%, B:SER1.N-A:HSD172.NE2 37.86%, B:SER1.N-A:PHE140.O 21.68%, A:VAL125.N-B:ALA7.O 16.48%, A:SER139.OG-B:GLY2.O 15.58%, A:SER10.N-B:SER10.OG 10.79%; in rep1: A:SER123.OG-B:VAL303.O 55.44%/B:SER123.OG-A:VAL303.O 54.25%, A:ARG4.NH1-B:GLU290.OE2 33.87%, A:ARG4.NH2-B:GLU290.OE1 21.58%, A:ARG4.NH1-B:GLU290.OE1 14.99%, A:ARG4.NH2-B:GLU290. OE2 10.69%/B:ARG4.NH1-A:GLU290.OE2 39.56%, B:ARG4.NH2A:GLU290.OE1 32.77%, B:ARG4.NH1-A:GLU290.OE1 22.08%, B:ARG4. NH2-A:GLU290.OE2 19.28%, A:PHE305.N-B:PRO122.O 33.17%/B:PHE305.N-A:PRO122.O 29.37%, A:ALA7.N-B:VAL125.O 31.77%/B:ALA7.N-A:VAL125.O 26.57%, A:PHE140.N-B:SER1.O 28.57%, A:GLY11.N-B:GLU14.OE2 23.68%/B:GLY11.N-A:GLU14.OE2 21.68%, A:SER1.N-B:GLU166.OE1 19.18%, A:SER1.N-B:GLU166.OE2 17.18%, A:SER1.N-B:HSD172.NE2 16.28%, A:SER1.N-B:PHE140.O 10.39%/B:SER 1.N-A:GLU166.OE2 24.48%, B:SER1.OG-A:GLU166.OE1 13.39%, B:SER 1.OG-A:GLU166.OE2 13.09%, B:SER1.N-A:HSD172.NE2 34.17%, B:SER1.
2.3 Results and Discussions
18. .− 19. 20.
21. 22. 23. 24. 25.
26. 27. 28.
51
N-A:PHE140.O 21.18%, B:PHE140.N-A:SER1.O 16.98%, A:SER139.OGB:GLY2.O 18.58%, A:VAL125.N-B:ALA7.O 17.98%/B:VAL125.N-A:ALA7.O 20.48%, in rep2: A:SER123.OG-B:VAL303.O 49.45%/B:SER123.OG-A:VAL303.O 55.74%, A:ARG4.NH1-B:GLU290.OE2 36.06%, A:ARG4.NH2-B:GLU290.OE1 23.78%, A:ARG4.NH1-B:GLU290.OE1 13.99%, A:ARG4.NH2-B:GLU290. OE2 10.69%/B:ARG4.NH1-A:GLU290.OE2 38.76%, B:ARG4.NH2A:GLU290.OE1 30.17%, B:ARG4.NH1-A:GLU290.OE1 20.68%, B:ARG4. NH2-A:GLU290.OE2 19.28%, A:PHE305.N-B:PRO122.O 33.07%/B:PHE305.N-A:PRO122.O 26.37%, A:ALA7.N-B:VAL125.O 29.07%/B:ALA7.N-A:VAL125.O 28.37% / B:VAL 125.N-A:ALA7.O 21.38%, A:PHE140.N-B:SER1.O 24.88%/B:PHE140.N-A:SER1.O 17.38%, A:GLY11.N-B:GLU14.OE2 22.78%/B:GLY11.N-A:GLU14.OE2 21.08%, A:SER1.N-B:GLU166.OE2 20.68%, A:SER1.N-B:GLU166.OE1 17.78%, A:SER1.N-B:HSD172.NE2 17.68%, A:SER1.N-B:PHE140.O 11.99%/B:SER 1.N-A:GLU166.OE2 23.88%, B:SER1.N-A:GLU166.OE1 22.18%, B:SER1. OG-A:GLU166.OE2 12.19%, B:SER1.OG-A:GLU166.OE1 10.49%, B:SER 1.N-A:HSD172.NE2 33.47%, B:SER1.N-A:PHE140.O 22.58%, A:SER139.OG-B:GLY2.O 16.18%, A:VAL125.N-B:ALA7.O 15.98%, A:SER10.N-B:SER10.OG 10.19%.
The REMD secondary structural developments for rep0-rep2 can be seen from Fig. 2.10, where we know that segments A:TYR37-A:LYS61 and B:ILE43B:LEU67 and residues A:PHE181 and B:ASP187 have unstable secondary structures during 50 ns’ MD rep0-rep2.
Fig. 2.10 The secondary structural graphs for the three sets of 50 ns’ REMD data in [113] for the 3CLpro-dimer (where from left to right are for rep0, rep1, and rep2, respectively, and 1 ns has 20 frames)
For the Evans-dimer model, Fig. 2.11 shows an important SB between GLU290 and ARG4 linking the two monomers and the RMSD performance of the three sets of REMD data in [113]. The polar contact between GLU290 and ARG4 linking the two monomers are strong.
52
2 3C-Like Protease (3CLpro)
Fig. 2.11 The SBs A:GLU290-B:ARG4 and B:GLU290-A:ARG4 linking the two monomers of the Evans-dimer model during the three sets of 50 ns’ REMD production phase and the RMSDs of the three sets of REMDs
In [340], six 6LU7-3CLpro models monomer_apo (aa 1–306, 4682 atoms), monomer_N3 (aa 1–306 + N3I 307, 4780 atoms), dimer_apo (aa 1–306 + aa 307– 612, 9364 atoms), dimer_N3 (aa 1–306 + aa 307–612 + N3I 613, 9642 atoms), dimer_2N3 (aa 1–306 + N3I 307 + aa 308–613 + N3I 614, 9560 atoms), and dimer_2N3_covalent (aa 1–306 + N3I 145 + aa 307–612 + N3I 451, 9562 atoms) are presented. We optimized the six models and list all their SBs in Table 2.8, where all the above SBs can be confirmed. HBs of the optimized six models of [340] are listed in Tables 2.9, 2.10, and 2.11. The .π -cations and .π -.π stackings of each model optimized are the following: ◦ 6LU7_monomer_apo: PHE8-ARG298.NH2+-PHE294; PHE103-TYR37, PHE3-PHE291, PHE219-TYR218; .◦ 6LU7_monomer_N3: TYR54-ARG40.NH2+, TYR101-LYS100.NZ+; HIS164HIS41, PHE103-TYR37, TRP207-PHE291; .◦ 6LU7_dimer_apo: TYR360-ARG494.NH2+; PHE409-TYR343, HIS469PHE446-HIS478-HIS469, HIS163-PHE140-HIS172-HIS163, PHE291-PHE3TRP207, PHE597-PHE309-TRP513, PHE219-TRP218, PHE525-TRP524; .◦ 6LU7_dimer_N3: PHE314-ARG604.NH2+, TYR237-LYS236.NZ+; TYR343PHE409, HIS469-HIS478-PHE446-HIS469, HIS163-PHE140, PHE103TYR37, TRP207-PHE3-TRP207-PHE291; .◦ 6LU7_dimer_2N3: TRP525-ARG586.NH2+, PHE315-ARG605.NH2+; HIS 163-PHE140-HIS172-HIS163, TYR37-PHE103, PHE3-TRP207, HIS470PHE447-HIS479, HIS387-PHE373, HIS348-HIS471; .◦ 6LU7_dimer_2N3_covalent: PHE305-LYS12.NZ+; TYR37-PHE103, TYR54HIS41-HIS164-PHE181, HIS163-HIS172-PHE140-HIS163, TRP524-PHE525TRP524, TYR360-HIS347, HIS478-HIS469-PHE446-HIS478. .
For the optimized models, the residues binding with the ligand N3 are the following: ◦ 6LU7_monomer_N3: THR25, LEU27, HIS41, SER46, MET49, LEU50, PHE140, LEU141, ASN142, GLY143, SER144, CYS145, 164, 165, 168, GLU166, GLN189, THR190, ALA191;
.
2.3 Results and Discussions
53
◦ 6LU7_dimer_2N3-N3I307: THR25, LEU27, HIS41, MET49, TYR54, PHE140, LEU141, ASN142, GLY143, SER144, CYS145, HIS163, HIS164, MET165, GLU166, LEU167, PRO168, HIS172, PHE181, VAL186, ASP187, ARG188, GLN189, THR190, ALA191, GLN192, ALA193, SER308; .◦ 6LU7_dimer_2N3-N3I614: SER1, THR331, THR333, HIS348, MET356, GLY450, SER451, CYS452, HIS470, HIS471, MET472, GLU473, LEU474, PRO475, PHE488, VAL493, ASP494, ARG495, GLN496, THR497, ALA498, GLN499; .◦ 6LU7_dimer_2N3_covalent-N3I145: THR25, THR26, LEU27, ASN28, PRO39, HIS41, MET49, TYR54, TYR118, LEU141, ASN142, GLY143, SER144, GLY146, SER147, HIS163, HIS164, MET165, GLU166, LEU167, PRO168, PHE181, ASP187, GLN189, THR190, ALA191, GLN192; .◦ 6LU7_dimer_2N3_covalent-N3I451: THR331, THR332, LEU333, ASN334, PRO345, HIS347, VAL348, CYS350, MET355, TYR360, ASN448, GLY449, SER450, GLY452, SER453, HIS469, HIS470, MET471, GLU472, LEU473, PHE487, VAL492, ASP493, GLN495, THR496, ALA497, GLN498 .
and they are shown in Fig. 2.12.
Fig. 2.12 The ligand interaction diagrams for the optimized 6LU7_monomer_N3, 6LU7_dimer_2N3-N3I307, 6LU7_dimer_2N3-N3I614, 6LU7_dimer_2N3_covalent-N3I145, and 6LU7_dimer_2N3_covalent-N3I451 models of [340], respectively (from left to right in turns)
For the six optimized models of [340], we also find some differences among them in secondary structures and Ramachandran plot distributions (Fig. 2.13).
54
2 3C-Like Protease (3CLpro)
Fig. 2.13 The secondary structures and Ramachandran plot diagrams of the optimized six models of [340]
Tables 2.12, 2.13, 2.14, 2.15, 2.16, 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, and 2.23 list all the SBs and HBs of MDs of the six models of [340], where each MD has five sets
2.3 Results and Discussions
55
of simulations, i.e., rep1-rep5, and all the above SBs and HBs of 3CLpro should be able to be confirmed from these Tables. Figures 2.24 and 2.25 show the secondary structures and RMSF performances of the MDs of [340].
2.3.3 Comparison with SARS-CoV-1-Mpro The PDB entry 1q2w is the X-ray crystal structure of the SARS-CoV-1 Mpro; it has AB-chains; A-chain has aa PHE3-SER301, MPD307, and aa HOH308-541; and Bchain has aa [SER-1-LEU0-]SER1-SER301 and aa HOH307-528, and the monomer has aa SER1-GLY306. The PDB entry 6y2e is the X-ray structure unliganded SARS-CoV-2-Mpro; it has A-chain aa SER1-GLN306, aa HOH401-713. In [346] the dimeric and monomeric MD trajectories for SARS-CoV-1-Mpro and SARSCoV-2-Mpro are without any ligand; for each model, there are three MD replicates. We denote the models as follows: ◦ ◦ .◦ .◦ . .
SARS-CoV-1-Mpro-1q2w-monomer-rep1, -rep2, -rep3, SARS-CoV-2-Mpro-6y2e-monomer-rep1, -rep2, -rep3, SARS-CoV-1-Mpro-1q2w-dimer-rep1, -rep2, -rep3, SARS-CoV-2-Mpro-6y2e-dimer-rep1, -rep2, -rep3.
The MD secondary structural developments during the 12 sets of MD simulations are shown in Fig. 2.14, where we can see the following: ◦ for the “SARS1 monomer” and “SARS2 monomer,” their .α-helices at Nand C-terminal segments aa ALA7-VAL13, TRP37-ILE43, MET49-LYS61, and ASP295-GLY304 are unstable and sometimes unfold, .◦ for the “SARS1 dimer,” the .α -helices in A-chain aa VAL36-LEU58, B-chain aa TYR54-SER65, and TER285-SER301 are unstable, and .◦ for the “SARS2 dimer,” the N-terminals’ .α-helices aa TYR37-LYS41 of A-chain and aa IL43-GLU55 of B-chain are unstable. .
The MD RMSD values are generally leveling off. The RMSF performances of the 12 sets of MD show that the segment aa 41–51 and residue 221 have larger RMSF values. The SBs and HBs (with occupancy rates .≥20%) of the 12 sets of MD can be seen in Tables 2.24 (MD-SBs of monomer of SARS-CoV-1/2-Mpro), Table 2.25 (MD-SBs of dimer of SARS-CoV-1/2-Mpro), Tables 2.26 and 2.27 (MD-HBs of monomer of SARS-CoV-1/2-Mpro), Tables 2.28, 2.29, and 2.30 (MD-HBs of dimer of SARS-CoV-1-Mpro), Tables 2.31, 2.32, and 2.33 (MD-HBs of dimer of SARSCoV-2-Mpro).
56
2 3C-Like Protease (3CLpro)
Fig. 2.14 The MD secondary structural developments during 500 frames (with frame stride = 10) of the four models: SARS-CoV-1-Mpro-1q2w-monomer (denoted as “SARS1 monomer”), SARSCoV-2-Mpro-6y2e-monomer (denoted as “SARS2 monomer”), SARS-CoV-1-Mpro-1q2w-dimer (denoted as “SARS1 dimer”), and SARS-CoV-2-Mpro-6y2e-dimer (denoted as “SARS2 dimer”) (from up to down in turns)—each model has three sets of MD simulations, rep1-rep3 (from left to right in turns)
2.3.4 Comparison with SARS-CoV-1-Mpro-N3 The PDB entry 2hob is the X-ray crystal structure of the SARS-CoV-1 Mpro in complex with the inhibitor N3; it has AB-chains, A-chain has aa SER1-GLN306 and aa HOH401-707, and B-chain has aa 02J1-ALA2-VAL3-LEU4-PJE5-010-6 and HOH101; in the MD datasets of [346], the SARS-CoV-1-Mpro-N3 monomer has aa SER1-GLN306 and ligand LIG307, and its dimer has LIG307 and LIG308, A-chain has aa SER1-GLN306, and B-chain has aa SER1-GLN306. The PDB entry 6lu7 is the X-ray structure unliganded SARS-CoV-2-Mpro in complex with the inhibitor N3; A-chain has aa SER1-GLN306 and aa HOH401-484 and C-chain has 02J1ALA2-VAL3-LEU4-PJE5-010-6; in the MD datasets of [346], the SARS-CoV-2Mpro-N3 monomer has aa SER1-GLN306 and ligand LIG307, and its dimer has LIG307 and LIG308, A-chain has aa SER1-GLN306, and B-chain has aa SER1GLN306. In the dimeric and monomeric MD trajectories of SARS-CoV-1-Mpro-N3
2.3 Results and Discussions
57
and SARS-CoV-2-Mpro-N3, each model has three MD replicates. We denote the models as: ◦ ◦ .◦ .◦ . .
SARS-CoV-1-Mpro-N3-2hob-monomer-rep1, -rep2, -rep3, SARS-CoV-2-Mpro-N3-6lu7-monomer-rep1, -rep2, -rep3, SARS-CoV-1-Mpro-N3-2hob-dimer-rep1, -rep2, -rep3, SARS-CoV-2-Mpro-N3-6lu7-dimer-rep1, -rep2, -rep3.
The MD secondary structural developments during the 12 sets of MD simulations are shown in Fig. 2.15, where we can see the following: ◦ For “SARS1-N3 monomer,” the .α -helices aa ALA7-VAL13 and ILE43-LYS61 unfold. .◦ For “SARS2-N3 monomer,” the .α -helices aa ALA7-VAL13, ILE43-LYS61, and ASP295-GLN306 (rep1 and rep3) unfold. .◦ For “SARS1-N3 dimer,” the .α -helix aa A:TYR37-A:LYS61, around B:ASP295, unfolds. .◦ For “SARS2-N3 dimer,” the .α -helices A:TYR37-A:LYS61 and B:ILE43B:LEU67, around B:295 (rep1), unfold. .
The MD RMSD values are generally leveling off. The SBs and HBs (with occupancy rates .≥20%) of the 12 sets of MD can be seen in Table 2.34 (MDSBs of monomer of SARS-CoV-1/2-Mpro-N3), Table 2.35 (MD-SBs of dimer of SARS-CoV-1/2-Mpro-N3), Table 2.36 (MD-HBs linking the monomer of SARSCoV-1/2-Mpro and the ligand LIG307), Tables 2.37 and 2.38 (MD-HBs of monomer of SARS-CoV-1/2-Mpro), Table 2.39 (MD-HBs linking the dimer of SARS-CoV-1Mpro and the two ligands LIG307 and LIG308, where for rep3 the ligand LIG307 has not been binding any residue of the dimer ARS-CoV-1 during the MD of rep3), Tables 2.40, 2.41, and 2.42 (MD-HBs of dimer of SARS-CoV-1-Mpro-N3), Table 2.43 (MD-HBs linking the dimer of SARS-CoV-2-Mpro and the two ligands LIG307 and LIG308), and Tables 2.44, 2.45, and 2.46 (MD-HBs of dimer of SARSCoV-2-Mpro-N3). The MD-HBs between the ligands and the dimer the SARS-CoV-1-MproN3-2hob model (denoted as “SARS-CoV-1-N3 dimer”) and the SARS-CoV-2Mpro-N3-6lu7 model (denoted as “SARS-CoV-2-N3 dimer”) can be seen in Tables 2.39, 2.40, 2.41, 2.42, and 2.43. The MD-SBs-HBs between the two monomers (denoted as A-chain and B-chain) of dimer the SARS-CoV-1-Mpro-N32hob model (denoted as “SARS-CoV-1-N3 dimer”) and the SARS-CoV-2-MproN3-6lu7 model (denoted as “SARS-CoV-2-N3 dimer”) can be seen in Table 2.48. Similarly, the MD-SBs-HBs polar contacts between the two monomers (denoted as A-chain and B-chain) of dimer the SARS-CoV-1-Mpro-1q2w model (denoted as “SARS-CoV-1 dimer”) and the SARS-CoV-2-Mpro-6y2e model (denoted as “SARS-CoV-2 dimer”) can be seen in Table 2.47. From these tables, we can easily know that the strong polar contact GLU290-ARG4 linking the two monomers of SARS-CoV-1-Mpro/SARS-CoV-2-Mpro/SARS-CoV-1-Mpro-N3/SARS-CoV-2Mpro-N3 dimer (Table 2.48).
58
2 3C-Like Protease (3CLpro)
Fig. 2.15 The MD secondary structural developments during 500 frames (with frame stride = 10) of the four models: SARS-CoV-1-Mpro-N3-2hob-monomer (denoted as “SARS1-N3 monomer”), SARS-CoV-2-Mpro-N3-6lu7-monomer (denoted as “SARS2-N3 monomer”), SARSCoV-1-Mpro-N3-2hob-dimer (denoted as “SARS1-N3 dimer”), and SARS-CoV-2-Mpro-N3-6lu7dimer (denoted as “SARS2-N3 dimer”) (from up to down in turns)—each model has three sets of MD simulations, rep1-rep3 (from left to right in turns). In the dimers, we denote the two monomers CD as A-chain and B-chain, respectively
We optimized the A-chain aa PHE3-SER301 of 1q2w.pdb (SARS-CoV1-Mpro) and the A-chain aa SER1-GLN306 with B-chain aa 02J1-ALA2VAL3-LEU4-PJE5-010-6 of 2hob.pdb (SARS-CoV-1-Mpro-N3). The 2hobmodel (SARS-CoV-1-Mpro-N3) has 4 .π -.π stackings, TRP218-PHE219, HID172-PHE140-HID163, PHE181-HID164-HID41, and PHE103-TYR37; 2 + + .π -cations, ARG298.NH2. -PHE8 and ARG105.NH2. -TYR182; and 14 SBs ASP34-LYS90, ASP56-ARG60, ASP92-ARG76, ASP153-LYS102, ASP155LYS12, ASP176-ARG105, ASP187-ARG40, ASP197-ARG131, ASP197LYS137, ASP229-LYS269, ASP289-ARG131, GLU288-LYS5, GLU290LYS5, and GLU290-ARG131;the SARS-CoV-1-Mpro residues (Fig. 2.16) bind with: ◦ 02J1: GLN192, THR190, ALA191, PRO168, B:ALA2, B:VAL3,
.
2.3 Results and Discussions
59
◦ ALA2-VAL3-LEU4: LEU167, GLN192, GLN189, THR190, ARG188, MET49, HID41, HID164, GLU166, MET165, .◦ PJE5: THR26, HID41, SER144, HID163, CYS145, PHE140, HID172, GLU166, LEU141, B:VAL3, B:LEU4, ASN142, HID164, LEU27, GLY143, MET49, .◦ 02J1-ALA2-VAL3-LEU4-PJE5-010-6: GLN189, LEU167, GLN192, THR190, PRO168, ALA191, HID41, MET49, HID164, ARG188, THR26, GLY143, LEU27, GLU166, PHE140, HID172, LEU141, CYS145, HID163, ASN142, SER144, MET165. .
The 1q2w-model (SARS-CoV-1-Mpro) has 2 .π -.π stackings, PHE103-TYR37 and HID172-PHE140-HID163, 1 .π -cation LYS236.NZ.+ -TYR237, and 14 SBs ASP34-LYS90, GLU55-ARG40, ASP56-ARG60, ASP92-ARG76, ASP153-LYS102, ASP155-LYS12, ASP176-ARG105, GLU178-LYS180, ASP187-ARG40, ASP197-ARG131, GLU288-LYS5, ASP289-ARG131, GLU290-LYS5, and ASP295-ARG298. Both the 2hob-
model (SARS-CoV-1-Mpro-N3) and the 1q2w-model (SARS-CoV-1-Mpro) have the same segment, i.e., ALA193-ALA194-GLY195, with low SASA values. Detailed MD-results of all these Mpro-wt monomer/dimer with/without ligand can be seen from Figs. 2.17, 2.18, 2.19, 2.20, 2.21, 2.22, 2.23, 2.24, and 2.25.
Fig. 2.16 The SARS-CoV-1-Mpro residues binding with the ligand N3 in the optimized 2hobmodel (SARS-CoV-1-Mpro-N3)
2.3.5 Variants 7BB2.pdb is the X-ray diffraction crystal structure of the main protease (3CLpro/Mpro) of SARS-COV-2 at 1.6 Å resolution (spacegroup P2(1)2(1)2(1)) [77], binding the model of MG-132 both to the Mpro of SARS-CoV-2 and to the human cathepsin L. MG-132 fits well into the Mpro active site, forming a covalent bond with Cys145 independently from reducing agents and crystallization conditions; docking of MG-132 into cathepsin L matches well with a covalent binding to the catalytic cysteine; and MG-132 inhibits cathepsin L with nanomolar potency and reversibly inhibits Mpro with micromolar potency [77]. 7BB2.pdb is the structure of Mpro-dimer with A-chain aa SER1-GLN306 and B-chain aa SER1-SER301. In [238], it is reported that the transmissible SARS-CoV-2 variants Mpro-delP168, Mpro-a173v, and Mpro-delP168-and-
60
2 3C-Like Protease (3CLpro)
a173v (Mpro-dm) have resistance to clinical protease inhibitors. Mpro-variants T45I, S46F, E47K, D48Y, M49I/L/T/V, S144A, M165I, P168S, .ΔP168, T169I, V171I, A173V/T/S, .ΔP168/A173V, T45I/M49L, T45I/A173V, T45I/.ΔP168, D48Y/.ΔP168, M49I/.ΔP168, and M49L/.ΔP168 are listed in Tables 1–3 of [238]. In the website amarolab.ucsd.edu/covid19.php, an openly accessible database “TRAJECTORIES_INPUTS_DATA_mpro_wt_variants_amarolab.tar.gz,” is listed, presenting the MD trajectories of the two monomers—in fact, we prefer the MD trajectories of the dimer. As follows we first build the three Mpro-variants by the use of 7BB2.pdb and then present some basic structural bioinformatics of the variants and the wild type (wt), confirmed by the analyses of the tar.gz file (Figs. 2.26, 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33 and 2.34). We built the dimers of the three models, Mpro-dm, Mpro-delP168, and Mpro-a173v, from 7BB2.pdb and then we optimized the four Mpro-wt, Mprodm, Mpro-delP168, and Mpro-a173v models with RMSD values 0.383307, 4.387699, 4.388842, and 4.382586 Å, respectively, from the unoptimized ones. For the optimized four models, it seems that they all have the same Na.+ ion binding residues, B:ASN221, B:PHE223, and B:ASP263 (B:ASN221.O, B:ASN221.OD1, B:PHE223.O, B:ASP263.O, B:ASP263.OD2 (salt bridge)), the same two .π -cations A:ARG222.NH2+-A:PHE223 and A:ARG298.NH2+A:PHE8, and the same 12 .π -.π stackings, B:TRP218-B:PHE219-B:TRP218, B:HIS163-B:HIS172-B:PHE140-B:HIS163, B:PHE181-B:HIS164, B:PHE103B:TYR37, A:HIS163-A:HIS172-A:PHE140-A:HIS163, A:PHE181-A:HIS164, and A:PHE103-A:TYR37. In addition, the optimized Mpro-wt model has one additional .π -.π stacking, A:PHE219-A:TRP218, and the optimized Mpro-a173v model has two additional .π -.π stackings, A:TRP218-A:PHE219-A:TRP218. All the four models have the low-SASA-value residues A:ALA193-A:ALA194-A:GLY195. All the four optimized models have the SBs A:GLU14-B:LYS12, A:GLU290B:ARG4, and B:GLU290-A:ARG4 linking the two monomers (Table 2.1) and there exist SBs ASP155-LYS100, ASP176-ARG105, ASP187-ARG40, ASP197ARG131, ASP197-LYS137, ASP289-ARG131, ASP34-LYS90, ASP56-ARG60, ASP92-ARG76, GLU166-HIS172, GLU288-LYS5, and GLU290-LYS5 within each monomer (Table 2.1). Besides the SBs A:GLU14-B:LYS12, A:GLU290-B:ARG4, and B:GLU290A:ARG4 linking the two monomers (Table 2.1), there are some HBs linking the two monomers (Table 2.2); we may easily see that the polar contacts between residues GLU290 and ARG4 contribute to the linkage of the two monomers. For the optimized models of the three variants and its wild type, Mpro-dm has an .α-helix aa A:GLY11-A:GLU14 around residue A:LYS12, but the .α-helix of the wt, delP168, a173v models seems to be turn-and-.310 -helix structures (Fig. 2.26). To confirm all the above structural bioinformatics of the wt and its three variants, we analyze the MD trajectories of the A-chain and B-chain. The 550 ns MDSB and MD-HB results can be seen in Tables 2.49, 2.50, 2.51, 2.52, 2.53, 2.54, 2.55, and 2.56. The SBs ASP155-LYS100, ASP176-ARG105, ASP187-ARG40, ASP197-ARG131, ASP197-LYS137, ASP289-ARG131, ASP34-LYS90, ASP56ARG60, ASP92-ARG76, GLU166-HIS172, GLU288-LYS5, and GLU290-LYS5
2.4 Concluding Remarks
61
within each monomer can be confirmed from Tables 2.49, 2.50, 2.51, and 2.52. The 550 ns MD secondary structures and MD-RMSF results are shown in Figs. 2.27, 2.28, 2.29, 2.30, 2.31, 2.32, 2.33, and 2.34. We know that for both the A-chain and B-chain, the segment aa TYR37-LYS61 is unstable during the 550 ns MDs, where aa TYR37-LYS61 consists of two .310 -helices, aa TYR37-ILE43 and aa ASP48-LEU50, and one .α-helix, aa ASP56-ILE59. The loop aa TYR182-ARG188 is also unstable for both monomers. In Fig. 2.29 for rep2, the B-chain C-terminal .α-helix aa 290-VAL296 sometimes unfolds into turns or .310 -helix during 0–303 ns. The MD-RMSF values are larger around residues ASN51, ALA191, and the C-terminals (Figs. 2.31, 2.32, 2.33, and 2.34); this agrees with the observations from Fig. 4A of [238]. For the SARS-CoV-2-Mpro 6lu7-monomer/dimer models without ligand, three sets (sim1-sim3) of 1ms MD databases are presented by the same first author of [353]. From the MD secondary structure performances, we may know the unstable segments are ILE43-LYS61 (sim1-sim3), SER139-CYS145 (sim2), ASP295-GLN306 (sim1, sim3) for the monomer-models, TYR37-LYS61 for the dimer A-chain, and ILE43-LEU67 and C-terminal around ASP295 for the dimer Bchain. The SBs GLU290-ARG4 (very strong) and GLU14-LYS12 (weak) link the two monomers. The linkage GLU290-ARG4 is a strong polar contact; between GLU290 and ARG4 there are HBs A:ARG4.NH2-B:GLU290.OE2 41.16%, A:ARG4.NH1-B:GLU290.OE1 37.46%, B:ARG4.NH1-A:GLU290.OE2 31.47%, B:ARG4.NH2-A:GLU290.OE1 27.57%, B:ARG4.NH1-A:GLU290.OE1 14.39%, A:ARG4.NH1-B:GLU290.OE2 13.49%, B:ARG4.NH2-A:GLU290.OE2 11.19%, A:ARG4.NH2-B:GLU290.OE1 10.99% in sim1; A:ARG4.NH2-B:GLU290.OE1 39.72%, A:ARG4.NH1-B:GLU290.OE2 35.33%, B:ARG4.NH1-A:GLU290.OE1 29.64%, B:ARG4.NH2-A:GLU290.OE2 29.14%, B:ARG4.NH1-A:GLU290.OE2 19.36%, B:ARG4.NH2-A:GLU290.OE1 16.57%,A:ARG4.NH1-B:GLU290.OE1 12.28% in sim2; and B:ARG4.NH1-A:GLU290.OE1 40.82%, B:ARG4.NH2A:GLU290.OE2 36.03%, A:ARG4.NH2-B:GLU290.OE2 22.75%, A:ARG4.NH1B:GLU290.OE1 22.36%, A:ARG4.NH1-B:GLU290.OE2 17.37%, A:ARG4.NH2B:GLU290.OE1 11.58% in sim3. It is also worth keeping an eye on all the HBs linking the two monomers.
2.4 Concluding Remarks This chapter studied the Mpro molecular structures with pdb entries 6LU7, 7BQY, 7BUY, 6Y84, and 7BB2 by optimization and MD strategies. In common, from almost all the models of the 3CLpro dimer, we found that sometimes, there are two polar contacts between GLU290 and ARG4 linking the two monomers. In comparison, in this chapter, we also studies the SARS-CoV-1-Mpro and SARSCoV-1-Mpro-N3 by optimization and MD strategies.
62
2 3C-Like Protease (3CLpro)
Supplementary Information
Fig. 2.17 Some SBs of the monomer 6LU7optimized model during the 100 ns MD production phase (where in all there are 1000 frames and the frame interval is 0.1 ns)
2.4 Concluding Remarks
63
Fig. 2.18 The secondary structural developments for the 6LU7optimized model during 100 ns MD
B:GLU290-A:ARG4
B:GLU290-A:ARG4
B:GLU290-A:ARG4
B:ASP229-B:LYS269
B:GLU166-B:HIS172
B:GLU288-B:LYS5
B:GLU290-B:LYS5
A:GLU166-A:HIS172
A:GLU288-A:LYS5
A:GLU290-A:LYS5
B:ASP56-B:ARG60
B:ASP92-B:ARG76
A:ASP56-A:ARG60
B:ASP48-B:ARG60
B:ASP34-B:LYS90
B:ASP295-B:ARG298
B:ASP289-B:ARG131
A:ASP92-A:ARG76
A:ASP34-A:LYS90
A:ASP289-A:ARG131
B:ASP197-B:ARG131
B:ASP197-B:LYS137
A:ASP197-A:ARG131
A:ASP197-A:LYS137 B:ASP229-B:LYS269
B:GLU290-B:LYS5
B:GLU166-B:HIS172 B:GLU288-B:LYS5
A:GLU166-A:HIS172
A:GLU288-A:LYS5
A:GLU290-A:LYS5
B:ASP92-B:ARG76
B:ASP56-B:ARG60
B:ASP48-B:ARG60
B:ASP34-B:LYS90
B:ASP295-B:ARG298
B:ASP289-B:ARG131
A:ASP92-A:ARG76
A:ASP56-A:ARG60
A:ASP34-A:LYS90
A:ASP289-A:ARG131
B:ASP197-B:ARG131 B:ASP197-B:LYS137
A:ASP197-A:ARG131
A:ASP197-A:LYS137
A:GLU290-A:LYS5
A:GLU288-A:LYS5
A:GLU166-A:HIS172
A:ASP92-A:ARG76
A:ASP56-A:ARG60
A:ASP34-A:LYS90
A:ASP289-A:ARG131
A:ASP197-A:LYS137
A:ASP197-A:ARG131
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP187-A:ARG40
A:ASP155-A:LYS12 A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP155-A:LYS12
A:ASP176-A:ARG105
A:ASP155-A:LYS12
A:ASP176-A:ARG105
B:ASP176-B:ARG105
B:ASP155-B:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS100
A:ASP155-A:LYS100
A:ASP155-A:LYS100
A:GLU290-B:ARG4
A:GLU290-B:ARG4
A:GLU290-B:ARG4
B:ASP153-B:LYS102
A:GLU14-B:LYS12
A:GLU14-B:LYS12
A:GLU14-B:LYS12
B:ASP153-B:LYS102
delP168-Mpro-7bb2
dm-Mpro-7bb2
wt-Mpro-7bb2
B:GLU290-B:LYS5
B:GLU288-B:LYS5
B:GLU166-B:HIS172
B:ASP92-B:ARG76
B:ASP56-B:ARG60
B:ASP48-B:ARG60
B:ASP34-B:LYS90
B:ASP295-B:ARG298
B:ASP289-B:ARG131
B:ASP229-B:LYS269
B:ASP197-B:LYS137
B:ASP197-B:ARG131
B:ASP187-B:ARG40
B:ASP176-B:ARG105
B:ASP155-B:LYS100
B:ASP153-B:LYS102
A:GLU290-A:LYS5
A:GLU288-A:LYS5
A:GLU166-A:HIS172
A:ASP92-A:ARG76
A:ASP56-A:ARG60
A:ASP34-A:LYS90
A:ASP289-A:ARG131
A:ASP197-A:LYS137
A:ASP197-A:ARG131
A:ASP187-A:ARG40
A:ASP176-A:ARG105
A:ASP155-A:LYS12
A:ASP155-A:LYS100
B:GLU290-A:ARG4
A:GLU290-B:ARG4
A:GLU14-B:LYS12
a173v-Mpro-7bb2
Table 2.1 All the SBs in the Mpro-wt, Mpro-delP168-and-a173v, Mpro-delP168, and Mpro-a173v dimer models are optimized
B:ASP153-B:LYS102
B:GLU290-B:LYS5
B:GLU288-B:LYS5
B:GLU166-B:HIS172
B:ASP92-B:ARG76
B:ASP56-B:ARG60
B:ASP48-B:ARG60
B:ASP34-B:LYS90
B:ASP295-B:ARG298
B:ASP289-B:ARG131
B:ASP229-B:LYS269
B:ASP197-B:LYS137
B:ASP197-B:ARG131
B:ASP187-B:ARG40
B:ASP176-B:ARG105
B:ASP155-B:LYS100
64 2 3C-Like Protease (3CLpro)
2.4 Concluding Remarks
65
Table 2.2 All the HBs linking the two monomers in the optimized Mpro-wt, Mpro-delP168-anda173v, Mpro-delP168, and Mpro-a173v dimer models wt-Mpro-7bb2
dm-Mpro-7bb2
delP168-Mpro-7bb2
a173v-Mpro-7bb2
A:ARG298.NH2-B:SER123.O
A:ARG298.NH2-B:SER123.O
A:ARG4.NH1-B:GLU290.OE2
A:ARG298.NH2-B:SER123.O
A:ARG4.NH1-B:GLU290.OE2
A:ARG4.NH1-B:GLU290.OE2
A:ARG4.NH2-B:GLU290.OE1
A:ARG4.NH1-B:GLU290.OE2
A:ARG4.NH2-B:GLU290.OE1
A:ARG4.NH2-B:GLU290.OE1
A:GLU290.OE1-B:ARG4.NH2
A:ARG4.NH2-B:GLU290.OE1
A:GLU290.OE1-B:ARG4.NH2
A:GLU290.OE1-B:ARG4.NH2
A:GLU290.OE2-B:ARG4.NH1
A:GLU290.OE1-B:ARG4.NH2
A:GLU290.OE2-B:ARG4.NH1
A:GLU290.OE2-B:ARG4.NH1
A:GLY11.N-B:GLU14.OE2
A:GLU290.OE2-B:ARG4.NH1
A:GLY11.N-B:GLU14.OE2
A:GLY11.N-B:GLU14.OE2
A:SER1.N-B:PHE140.O
A:GLY11.N-B:GLU14.OE2
A:SER1.N-B:PHE140.O
A:SER1.N-B:PHE140.O
A:SER1.OG-B:GLU166.OE2
A:SER1.N-B:PHE140.O
A:SER1.OG-B:GLU166.OE2
A:SER1.OG-B:GLU166.OE2
A:SER10.N-B:SER10.OG
A:SER1.OG-B:GLU166.OE2
A:SER10.N-B:SER10.OG
A:SER10.N-B:SER10.OG
A:SER139.OG-B:GLN299.OE1
A:SER10.N-B:SER10.OG
A:SER139.OG-B:GLN299.OE1
A:SER139.OG-B:GLN299.OE1
A:VAL125.N-B:ALA7.O
A:VAL125.N-B:ALA7.O
B:ALA7.N-A:VAL125.O
B:ALA7.N-A:VAL125.O
A:VAL125.N-B:ALA7.O
A:SER139.OG-B:GLN299.OE1
B:ALA7.N-A:VAL125.O
B:ALA7.N-A:VAL125.O
A:VAL125.N-B:ALA7.O
B:ARG4.NH1-A:GLU290.OE2
B:ARG4.NH1-A:GLU290.OE2
B:ARG4.NH1-A:GLU290.OE2
B:ARG4.NH1-A:GLU290.OE2
B:ARG4.NH2-A:GLU290.OE1
B:ARG4.NH2-A:GLU290.OE1
B:ARG4.NH2-A:GLU290.OE1
B:ARG4.NH2-A:GLU290.OE1
B:GLU290.OE1-A:ARG4.NH2
B:GLU290.OE1-A:ARG4.NH2
B:GLU290.OE1-A:ARG4.NH2
B:GLU290.OE1-A:ARG4.NH2
B:GLY11.N-A:GLU14.OE2
B:PHE140.N-A:SER1.O
B:GLY11.N-A:GLU14.OE2
B:PHE140.N-A:SER1.O
B:PHE140.N-A:SER1.O
B:SER1.N-A:PHE140.O
B:PHE140.N-A:SER1.O
B:SER1.N-A:PHE140.O
B:SER1.N-A:PHE140.O
B:SER1.OG-A:GLU166.OE2
B:SER1.N-A:PHE140.O
B:SER1.OG-A:GLU166.OE2
B:SER1.OG-A:GLU166.OE2
B:SER139.OG-A:GLN299.OE1
B:SER1.OG-A:GLU166.OE2
B:SER139.OG-A:GLN299.OE1
B:SER139.OG-A:GLN299.OE1
B:SER139.OG-A:GLN299.OE1
Fig. 2.19 Some SBs of the dimer 6Y84optimized model during the 100 μs MD production phase
66
Fig. 2.19 (continued)
2 3C-Like Protease (3CLpro)
2.4 Concluding Remarks
67
Fig. 2.20 The secondary structural developments for dimeric 3CLpro of the 6Y84optimized model during 100 μs MD
68
2 3C-Like Protease (3CLpro)
Fig. 2.21 Some SBs of the dimer 6LU7optimized model during the 10,000 ns MD-Traj1 production phase
2.4 Concluding Remarks
69
Fig. 2.22 Some SBs of the dimer 6LU7optimized model during the 10,000 ns MD-Traj2 production phase
70
2 3C-Like Protease (3CLpro)
Fig. 2.23 Some SBs of the Evans-dimer model during the three sets of 50 ns REMD production phase
2.4 Concluding Remarks
Fig. 2.23 (continued)
71
72 Table 2.3 The HBs with occupancy rate greater than 50% of the MD of [102] for the 6LU7optimized model
Table 2.4 The HBs with more than 50% occupancy rates during the 100 μs MD simulations for the 6Y84-dimer model
2 3C-Like Protease (3CLpro) Occupancy
Donor-acceptor
85.91%
A:ARG131@NH2-A:ASP289.OD2
80.62%
A:ARG40.NH2-A:ASP187.OD1
80.22%
A:ARG131.NH1-A:ASP289.OD1
68.63%
A:TRP31.N-A:CYS16.O
66.73%
A:VAL36.N-A:LEU89.O
65.53%
A:ILE78.N-A:LYS90.O
64.24%
A:ASN95.N-A:ASP33.O
60.84%
A:THR201.OG1-A:GLU240.O
60.84%
A:LEU87.N-A:CYS38.O
59.04%
A:VAL114.N-A:TYR126.O
58.34%
A:HIP164.NE2-A:ASP187.OD2
58.24%
A:PHE8.N-A:SER113.OG
58.04%
A:ARG131.N-A:THR135.O
57.54%
A:ARG40.NE-A:ASP187.OD2
56.54%
A:ALA70.N-A:VAL73.O
56.24%
A:GLN256.NE2-A:VAL303.O
55.94%
A:LYS88.N-A:SER81.O
54.65%
A:TYR182.OH-A:CYS160.O
54.15%
A:GLN83.N-A:VAL86.O
53.15%
A:LEU89.N-A:VAL36.O
53.15%
A:VAL20.N-A:LEU27.O
51.35%
A:LYS5.NZ-A:GLU288.OE2
51.05%
A:ASN221.N-A:SER267.OG
50.95%
A:ASN231.N-A:LEU227.O
50.55%
A:ARG105.NH2-A:PHE181.O
50.35%
A:ALA116.N-A:GLY124.O
50.25%
A:HIS163.N-A:SER147.O
50.15%
A:SER267.OG-A:ASP263.O
49.75%
A:ASN28.ND2-A:CYS145.O
49.05%
A:TYR209.OH-A:ILE259.O
Donor
Acceptor
Occupancy
TRP31.N
CYS16.O
93.41%
GLY149.N
TYR161.O
91.91%
LYS88.N
SER81.O
88.71%
TYR182.OH
CYS160.O
87.31%
GLY109.N
MET130.O
86.81%
VAL36.N
LEU89.O
86.61%
VAL114.N
TYR126.O
85.91%
LEU89.N
VAL36.O
84.72%
PHE8.N
SER113.OG
84.42%
VAL157.N
LYS100.O
84.12%
THR201.OG1
GLU240.O
83.12%
LEU167.N
VAL171.O
81.22%
SER123.N
ALA116.O
80.82%
LEU87.N
CYS38.O
80.82%
LEU75.N
VAL68.O
80.72%
ALA210.N
ALA206.O
80.12%
GLN299.NE2
ARG4.O
79.72%
MET130.N
GLN110.O
78.82%
LEU30.N
TYR37.O
76.92%
GLN256.N
PRO252.O
76.82%
TYR37.N
LEU30.O
76.52%
GLN83.N
VAL86.O
76.12%
ASN231.N
LEU227.O
75.32%
TYR182.N
GLY174.O
74.63%
LYS269.N
CYS265.O
73.73%
HIS163.N
SER147.O
73.53%
TYR209.OH
ILE259.O
73.43%
LEU268.N
MET264.O
73.03%
(continued)
2.4 Concluding Remarks Table 2.4 (continued)
73
Donor
Acceptor
Occupancy
TYR54.OH
ASP187.O
72.83%
TYR118.N
SER121.O
71.83%
LEU115.N
VAL148.O
71.83%
VAL91.N
ASP34.O
71.53%
ASN95.N
ASP33.O
71.33%
ALA255.N
GLY251.O
71.03%
VAL20.N
LEU27.O
70.73%
ALA234.N
PHE230.O
70.73%
ARG40.NH2
ASP187.OD1
70.63%
LEU242.N
ASN231.OD1
70.43%
TYR239.N
ALA234.O
70.23%
THR21.N
LEU67.O
69.83%
ALA70.N
VAL73.O
69.73%
ARG40.NE
ASP187.OD2
69.63%
LEU27.N
VAL20.O
69.53%
ARG298.N
PHE294.O
69.23%
ILE78.N
LYS90.O
69.03%
GLY29.N
VAL18.O
67.53%
SER113.N
PHE150.O
67.33%
ASN95.ND2
TRP31.O
67.23%
ALA173.N
MET165.O
67.03%
SER254.OG
ILE259.O
67.03%
SER10.OG
GLU14.OE1
66.93%
GLN19.N
GLN69.O
66.03%
ARG105.NH2
PHE181.O
65.83%
CYS265.N
VAL261.O
65.03%
CYS22.N
THR25.O
64.64%
LYS90.N
GLY79.O
64.44%
PHE150.N
SER113.O
63.84%
CYS128.N
PHE112.O
63.54%
ASP153.N
CYS156.O
62.84%
GLN273.N
LYS269.O
62.04%
VAL18.N
GLY29.O
61.04%
ALA206.N
VAL202.O
61.04%
LEU205.N
THR201.O
59.74%
HIS80.ND1
ASN63.OD1
59.24%
SER254.N
LEU250.O
58.74%
ILE213.N
TYR209.O
58.44%
ARG4.N
GLN299.OE1
58.24%
HIS41.NE2
HIS164.O
58.04%
VAL297.N
PRO293.O
57.54%
ILE281.N
SER284.O
57.34%
LEU57.N
ASN53.O
57.14%
GLY11.N
GLU14.OE1
56.44%
TYR209.N
LEU205.O
56.14%
ASP248.N
GLN244.O
55.14%
SER158.N
ASN151.O
54.85%
LYS5.NZ
GLU290.OE2
54.25%
THR199.N
ASN238.O
53.75%
LEU67.N
THR21.O
53.65%
LEU272.N
LEU268.O
53.45%
ASN221.N
SER267.OG
53.25%
ASN274.N
GLU270.O
53.15%
LYS5.NZ
GLU290.OE1
52.95%
LEU32.N
VAL35.O
52.65%
GLN107.N
GLN110.OE1
52.25%
MET235.N
ASN231.O
51.75%
THR257.OG1
LEU253.O
51.25%
ASN214.N
ALA210.O
51.15%
CYS160.N
GLY149.O
50.85%
GLY120.N
ASN28.OD1
50.55%
GLN192.NE2
VAL186.O
50.35%
CYS300.N
VAL296.O
50.25%
LYS102.N
VAL157.O
50.15%
PHE134.N
ARG131.O
50.15%
74 Table 2.5 The HBs with more than 50% occupancy rates during the 10 μs Traj1-MD simulations for the 6LU7-dimer model
2 3C-Like Protease (3CLpro) Donor
Acceptor
Occupancy
SER10.OG
GLU14.OE2
89.81%
TYR209.OH
ILE259.O
87.51%
SER267.OG
ASP263.O
87.31%
TYR182.OH
CYS160.O
84.22%
ILE78.N
LYS90.O
82.72%
TRP31.N
CYS16.O
82.42%
THR201.OG1
GLU240.O
81.32%
SER147.OG
SER144.O
80.32%
HIS163.N
SER147.O
79.72%
THR257.OG1
LEU253.O
78.42%
VAL36.N
LEU89.O
77.02%
VAL114.N
TYR126.O
75.62%
LYS88.N
SER81.O
73.93%
LEU87.N
CYS38.O
73.43%
LEU27.N
VAL20.O
72.93%
TYR37.N
LEU30.O
72.83%
VAL157.N
LYS100.O
72.53%
LEU115.N
VAL148.O
72.23%
LEU89.N
VAL36.O
71.33%
GLY149.N
TYR161.O
70.13%
GLN19.N
GLN69.O
69.93%
PHE150.N
SER113.O
69.53%
ASP153.N
CYS156.O
69.33%
LYS90.N
GLY79.O
68.53%
LEU242.N
ASN231.OD1
68.33%
ASN95.N
ASP33.O
67.73%
ALA70.N
VAL73.O
67.63%
CYS128.N
PHE112.O
67.33%
LEU75.N
VAL68.O
66.93%
VAL20.N
LEU27.O
66.33%
SER123.N
ALA116.O
66.13%
THR175.OG1
ASP176.O
65.93%
HIS172.N
ILE136.O
65.93%
THR135.OG1
ASN133.OD1
65.43%
ILE281.N
SER284.O
65.13%
TYR118.N
SER121.O
64.94%
ASN203.ND2
ASP289.O
64.64%
ALA173.N
MET165.O
64.44%
LEU167.N
VAL171.O
63.94%
VAL18.N
GLY29.O
63.44%
THR199.N
ASN238.O
62.94%
GLN83.N
VAL86.O
62.64%
LEU30.N
TYR37.O
62.24%
GLY146.N
HIS163.O
61.94%
ASN28.ND2
CYS145.O
61.54%
VAL91.N
ASP34.O
60.84%
GLY109.N
MET130.O
60.34%
TYR182.N
GLY174.O
59.94%
LEU205.N
THR201.O
59.74%
GLN192.NE2
VAL186.O
58.54%
TYR239.N
ALA234.O
58.54%
ARG131.N
THR135.O
58.34%
LEU32.N
VAL35.O
57.64%
ASN203.ND2
GLY109.O
57.34%
PHE8.N
SER113.OG
57.14%
PHE112.N
CYS128.O
56.94%
ASN95.ND2
TRP31.O
56.54%
GLU14.N
SER10.O
55.24%
THR45.OG1
ASP48.OD2
53.55%
SER158.N
ASN151.O
53.15%
ASN231.N
LEU227.O
53.05%
THR21.N
LEU67.O
51.95%
CYS160.N
GLY149.O
50.15%
2.4 Concluding Remarks Table 2.6 The HBs with more than 50% occupancy rates during the 10 μs Traj2-MD simulations for the 6LU7-dimer model
75 Donor
Acceptor
Occupancy
SER10.OG
GLU14.OE1
88.91%
TYR209.OH
ILE259.O
88.71%
SER267.OG
ASP263.O
87.51%
TRP31.N
CYS16.O
86.11%
THR201.OG1
GLU240.O
85.21%
TYR182.OH
CYS160.O
83.82%
ILE78.N
LYS90.O
80.42%
THR257.OG1
LEU253.O
78.72%
VAL114.N
TYR126.O
76.92%
VAL36.N
LEU89.O
76.52%
HIS163.N
SER147.O
75.62%
SER123.N
ALA116.O
75.12%
SER147.OG
SER144.O
74.43%
LEU89.N
VAL36.O
73.73%
TYR37.N
LEU30.O
73.03%
LYS88.N
SER81.O
71.43%
LEU167.N
VAL171.O
71.03%
PHE150.N
SER113.O
70.63%
LEU87.N
CYS38.O
70.43%
LEU27.N
VAL20.O
70.43%
GLY149.N
TYR161.O
69.23%
ASN95.N
ASP33.O
69.03%
LEU115.N
VAL148.O
68.43%
GLN19.N
GLN69.O
68.13%
LYS90.N
GLY79.O
68.03%
GLY109.N
MET130.O
67.93%
VAL20.N
LEU27.O
67.43%
LEU75.N
VAL68.O
66.93%
ALA70.N
VAL73.O
66.73%
VAL157.N
LYS100.O
66.43%
THR175.OG1
ASP176.O
66.03%
TYR118.N
SER121.O
65.53%
HIS172.N
ILE136.O
65.33%
CYS128.N
PHE112.O
65.13%
PHE8.N
SER113.OG
64.14%
GLY146.N
HIS163.O
64.04%
ASP153.N
CYS156.O
64.04%
ASN28.ND2
CYS145.O
63.74%
TYR182.N
GLY174.O
63.64%
PHE112.N
CYS128.O
62.94%
ASN203.ND2
ASP289.O
61.54%
GLN83.N
VAL86.O
61.34%
ALA173.N
MET165.O
61.34%
LEU30.N
TYR37.O
61.04%
ASN95.ND2
TRP31.O
60.94%
LEU32.N
VAL35.O
60.14%
THR199.N
ASN238.O
59.84%
VAL18.N
GLY29.O
59.54%
ILE281.N
SER284.O
59.34%
ARG105.NH2
PHE181.O
58.14%
VAL91.N
ASP34.O
57.54%
THR135.OG1
ASN133.OD1
56.34%
LEU205.N
THR201.O
56.34%
GLU14.N
SER10.O
55.54%
THR21.N
LEU67.O
54.65%
SER158.N
ASN151.O
54.35%
LEU242.N
ASN231.OD1
53.35%
ASN231.N
LEU227.O
50.75%
THR292.OG1
ASP295.OD1
50.15%
76
2 3C-Like Protease (3CLpro)
Table 2.7 The HBs with more than 50% occupancy rates during the three sets of 50 μs REMD rep0-rep1-rep3 for the Evans-dimer model rep0
rep1
rep2
A:ARG40.NE-A:ASP187.OD2 79.12%
A:ARG40.NE-A:ASP187.OD2 77.32%
A:TRP31.N-A:CYS16.O 75.02%
A:TRP31.N-A:CYS16.O 73.83%
A:TRP31.N-A:CYS16.O 77.02%
A:ARG40.NE-A:ASP187.OD2 73.63%
A:HSD163.N-A:SER147.O 69.33%
A:HSD163.N-A:SER147.O 69.43%
A:HSD163.N-A:SER147.O 68.53%
A:VAL36.N-A:LEU89.O 68.83%
A:VAL36.N-A:LEU89.O 69.43%
A:VAL36.N-A:LEU89.O 67.23%
A:TYR182.OH-A:CYS160.O 67.23%
A:TYR182.OH-A:CYS160.O 68.93%
A:TYR182.OH-A:CYS160.O 66.63%
A:GLY149.N-A:TYR161.O 65.73%
A:VAL20.N-A:LEU27.O 63.04%
A:TYR37.N-A:LEU30.O 61.64%
A:LEU89.N-A:VAL36.O 64.54%
A:GLY149.N-A:TYR161.O 61.94%
A:LEU89.N-A:VAL36.O 60.64%
A:SER267.OG-A:ASP263.O 61.84%
A:TYR37.N-A:LEU30.O 61.04%
A:VAL20.N-A:LEU27.O 60.64%
A:ASN95.N-A:ASP33.O 61.24%
A:SER267.OG-A:ASP263.O 60.94%
A:SER254.OG-A:ILE259.O 58.14%
A:VAL20.N-A:LEU27.O 61.24%
A:ASN95.N-A:ASP33.O 59.64%
A:SER267.OG-A:ASP263.O 57.44%
A:SER254.OG-A:ILE259.O 61.14%
A:LEU89.N-A:VAL36.O 58.74%
A:ASN95.N-A:ASP33.O 57.04%
A:TYR37.N-A:LEU30.O 59.94%
A:ARG40.NH2-A:ASP187.OD1 58.54%
A:GLY146.N-A:HSD163.O 56.84%
A:ARG40.NH2-A:ASP187.OD1 58.84%
A:SER254.OG-A:ILE259.O 58.14%
A:GLY149.N-A:TYR161.O 56.84%
A:GLY146.N-A:HSD163.O 57.34%
A:THR21.N-A:LEU67.O 56.04%
A:LYS88.N-A:SER81.O 56.44%
A:LEU167.N-A:VAL171.O 57.34%
A:SER123.OG-B:VAL303.O 55.44%
A:ARG105.NH2-A:PHE181.O 56.24%
A:ALA173.N-A:MET165.O 56.94%
A:GLY146.N-A:HSD163.O 55.04%
A:THR257.OG1-A:LEU253.O 55.24%
A:ARG105.NH2-A:PHE181.O 56.74%
A:LYS88.N-A:SER81.O 54.95%
A:ALA173.N-A:MET165.O 55.04%
A:LYS88.N-A:SER81.O 54.95%
A:LEU167.N-A:VAL171.O 54.75%
A:LEU167.N-A:VAL171.O 53.35%
A:THR257.OG1-A:LEU253.O 54.85%
A:ARG105.NH2-A:PHE181.O 54.15%
A:ARG40.NH2-A:ASP187.OD1 52.45%
A:VAL114.N-A:TYR126.O 54.25%
A:VAL157.N-A:LYS100.O 54.05%
A:ARG131.NH2-A:ASP289.OD2 52.15%
A:ASN180.N-A:ASP176.OD1 53.85%
A:ALA173.N-A:MET165.O 52.95%
A:SER10.OG-A:GLU14.OE2 51.45%
A:ARG298.N-A:PHE294.O 53.75%
A:THR257.OG1-A:LEU253.O 52.45%
A:SER144.OG-A:LEU141.O 51.45%
A:SER123.OG-B:VAL303.O 53.65%
A:VAL114.N-A:TYR126.O 52.35%
A:THR21.N-A:LEU67.O 51.15%
A:SER144.OG-A:LEU141.O 53.65%
A:ASN180.N-A:ASP176.OD1 52.15%
A:LYS90.N-A:GLY79.O 50.45%
A:LYS90.N-A:GLY79.O 52.15%
A:ASN231.N-A:LEU227.O 51.95%
A:VAL114.N-A:TYR126.O 50.15%
A:ILE78.N-A:LYS90.O 51.95%
A:ARG131.NH2-A:ASP289.OD2 51.85%
A:ASN231.N-A:LEU227.O 51.85%
A:SER144.OG-A:LEU141.O 51.65%
A:THR21.N-A:LEU67.O 51.55%
A:ILE78.N-A:LYS90.O 50.65%
A:SER301.OG-A:VAL297.O 50.05%
A:LYS90.N-A:GLY79.O 50.45%
B:TRP31.N-B:CYS16.O 74.23%
B:TRP31.N-B:CYS16.O 73.63%
B:TRP31.N-B:CYS16.O 73.43%
B:VAL36.N-B:LEU89.O 71.13%
B:VAL36.N-B:LEU89.O 70.53%
B:VAL36.N-B:LEU89.O 70.83%
B:ARG40.NE-B:ASP187.OD2 68.23%
B:HSD163.N-B:SER147.O 68.23%
B:ARG40.NE-B:ASP187.OD2 68.33%
B:HSD163.N-B:SER147.O 68.13%
B:TYR182.OH-B:CYS160.O 65.33%
B:HSD163.N-B:SER147.O 66.43%
B:SER267.OG-B:ASP263.O 64.34%
B:ARG40.NE-B:ASP187.OD2 65.23%
B:TYR182.OH-B:CYS160.O 64.64%
B:TYR182.OH-B:CYS160.O 63.44%
B:SER267.OG-B:ASP263.O 61.94%
B:TYR37.N-B:LEU30.O 60.14%
B:TYR37.N-B:LEU30.O 62.84%
B:TYR37.N-B:LEU30.O 61.34%
B:GLY146.N-B:HSD163.O 59.04%
B:SER254.OG-B:ILE259.O 62.44%
B:SER10.OG-B:GLU14.OE2 61.04%
B:ASN95.N-B:ASP33.O 58.64%
B:SER10.OG-B:GLU14.OE2 60.54%
B:ASN95.N-B:ASP33.O 60.84%
B:LEU89.N-B:VAL36.O 58.14%
B:ASN95.N-B:ASP33.O 59.54%
B:GLY146.N-B:HSD163.O 60.34%
B:SER267.OG-B:ASP263.O 57.44%
B:LEU89.N-B:VAL36.O 58.94%
B:LEU89.N-B:VAL36.O 59.74%
B:GLY149.N-B:TYR161.O 57.14%
B:VAL20.N-B:LEU27.O 58.44%
B:GLY149.N-B:TYR161.O 58.44%
B:ARG131.NH2-B:ASP289.OD2 57.04%
B:GLY146.N-B:HSD163.O 57.24%
B:ARG131.NH2-B:ASP289.OD2 58.24%
B:SER254.OG-B:ILE259.O 56.04%
B:GLY149.N-B:TYR161.O 57.14%
B:VAL20.N-B:LEU27.O 56.94%
B:SER123.OG-A:VAL303.O 55.74%
B:SER301.OG-B:VAL297.O 57.14%
B:LEU167.N-B:VAL171.O 56.84%
B:LEU167.N-B:VAL171.O 55.24%
B:LEU167.N-B:VAL171.O 56.44%
B:SER254.OG-B:ILE259.O 56.74%
B:SER10.OG-B:GLU14.OE2 55.04%
B:ARG131.NH2-B:ASP289.OD2 55.84%
B:ARG40.NH2-B:ASP187.OD1 55.54%
B:ALA173.N-B:MET165.O 54.95%
B:LEU87.N-B:CYS38.O 55.74%
B:LEU87.N-B:CYS38.O 55.34%
B:VAL20.N-B:LEU27.O 54.65%
B:LYS88.N-B:SER81.O 55.14%
B:ARG105.NH2-B:PHE181.O 55.24%
B:LEU87.N-B:CYS38.O 54.45%
B:ALA173.N-B:MET165.O 54.15%
B:SER301.OG-B:VAL297.O 54.95%
B:ARG40.NH2-B:ASP187.OD1 54.25%
B:SER123.OG-A:VAL303.O 53.35%
B:VAL114.N-B:TYR126.O 54.35%
B:ILE78.N-B:LYS90.O 53.85%
B:VAL114.N-B:TYR126.O 52.75%
B:SER123.OG-A:VAL303.O 54.25%
B:ARG105.NH2-B:PHE181.O 53.35%
B:ARG105.NH2-B:PHE181.O 52.65%
B:ALA173.N-B:MET165.O 53.85%
B:SER301.OG-B:VAL297.O 52.05%
B:LYS90.N-B:GLY79.O 52.45%
B:ILE78.N-B:LYS90.O 53.15%
B:VAL114.N-B:TYR126.O 52.05%
B:ASN231.N-B:LEU227.O 51.85%
B:ARG298.N-B:PHE294.O 52.75%
B:THR257.OG1-B:LEU253.O 51.05%
B:SER144.OG-B:LEU141.O 51.75%
B:LYS90.N-B:GLY79.O 52.75%
B:ARG40.NH2-B:ASP187.OD1 51.65%
B:SER144.OG-B:LEU141.O 51.45%
B:LEU75.N-B:VAL68.O 51.55%
B:ASN231.N-B:LEU227.O 51.05%
B:THR257.OG1-B:LEU253.O 51.25%
B:THR111.OG1-B:ASP295.OD2 50.85%
B:ARG298.N-B:PHE294.O 50.75%
B:THR257.OG1-B:LEU253.O 50.65%
B:THR201.OG1-B:GLU240.O 50.75%
B:THR201.OG1-B:GLU240.O 50.45% B:LYS88.N-B:SER81.O 50.15%
2.4 Concluding Remarks
77
Table 2.8 SBs of the optimized six models of [340] Monomer-apo
Monomer-N3
Dimer-apo
Dimer-N3
Dimer-2N3
Dimer-2N3-covalent
ASP153-LYS102
ASP155-LYS12
A-B-chains
A-B-chains
A-B-chains
A-B-chains
ASP155-LYS100
ASP187-ARG188
GLU14-LYS318
GLU290-ARG310
GLU14-LYS319
GLU290-ARG310
ASP176-ARG105
ASP187-ARG40
GLU596-ARG4
GLU320-LYS12
GLU290-ARG311
In A-chain
ASP187-ARG40
ASP187-HIS41
In A-chain
GLU596-ARG4
GLU597-ARG4
ASP34-LYS90
ASP197-ARG131
ASP197-ARG131
ASP34-LYS90
In A-chain
In A-chain
ASP48-LYS61
ASP197-LYS137
ASP197-LYS137
ASP48-LYS61
ASP34-LYS90
ASP34-LYS90
GLU55-ARG188
ASP229-LYS269
ASP229-LYS269
ASP56-ARG60
ASP48-ARG60
GLU55-ARG40
ASP56-ARG60
ASP289-ARG131
ASP263-ARG222
ASP92-ARG76
ASP48-LYS61
ASP56-ARG60
ASP92-ARG76
ASP295-ARG298
ASP289-ARG131
ASP153-LYS102
GLU55-ARG188
ASP92-ARG76
ASP153-LYS102
ASP34-LYS90
ASP295-ARG298
ASP155-LYS100
ASP92-ARG76
ASP153-LYS102
ASP155-LYS100
ASP56-ARG60
ASP34-LYS90
GLU166-HIS172
ASP153-LYS102
ASP155-LYS12
GLU166-HIS172
ASP92-ARG76
ASP56-ARG60
ASP176-ARG105
ASP155-LYS100
ASP155-LYS100
ASP176-ARG105
GLU290-ARG131
ASP92-ARG76
ASP187-ARG40
GLU166-HIS172
GLU166-HIS172
GLU178-LYS88
GLU166-HIS172
ASP197-ARG131
ASP176-ARG105
ASP176-ARG105
ASP187-ARG40
GLU178-LYS88
ASP229-LYS269
ASP187-ARG40
GLU178-LYS88
ASP187-ARG188
GLU288-LYS5
GLU270-ARG222
ASP197-ARG131
ASP187-ARG40
ASP197-ARG131
GLU290-ARG131 GLU290-LYS5
GLU288-LYS5
ASP245-HIS246
ASP197-ARG131
ASP263-ARG222
ASP289-ARG131
ASP263-ARG222
ASP197-LYS137
GLU270-LYS269
GLU290-LYS5
GLU270-LYS269
GLU270-LYS269
GLU288-LYS5
GLU290-ARG310
GLU288-LYS5
GLU288-LYS5
GLU288-LYS137
ASP295-ARG298
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
In B-chain
GLU290-LYS5
GLU290-LYS5
GLU290-LYS5
GLU320-LYS12
ASP295-ARG298
In B-chain
ASP295-ARG298
ASP362-ARG366
In B-chain
ASP341-LYS397
In B-Chain
ASP340-LYS396
GLU361-ARG346
ASP355-ARG367
ASP340-LYS396
ASP398-ARG382
GLU361-ARG494
ASP363-ARG367
ASP354-LYS367
ASP461-LYS406
ASP340-LYS396
ASP399-ARG383
GLU361-ARG346
GLU472-HIS469
ASP362-ARG366
ASP460-LYS409
ASP362-ARG366
ASP482-ARG411
ASP398-ARG382
ASP462-LYS407
ASP398-ARG382
GLU484-LYS408
ASP459-LYS408
GLU473-HIS479
ASP459-LYS408
ASP493-ARG346
ASP461-LYS318
ASP483-ARG412
ASP461-LYS318
ASP503-ARG437
ASP461-LYS406
GLU485-LYS395
GLU472-HIS478
ASP503-LYS443
GLU472-HIS478
ASP494-ARG347
ASP482-ARG411
ASP569-ARG528
ASP482-ARG411
ASP504-ARG438
GLU484-LYS394
GLU594-LYS311
GLU484-ARG411
ASP504-LYS444
ASP493-ARG346
ASP595-ARG437
ASP493-ARG346
GLU577-LYS576
ASP493-HIS347
GLU596-LYS311
ASP503-ARG437
GLU595-LYS312
ASP503-ARG437
ASP601-ARG604
ASP535-LYS575
ASP596-ARG438
ASP503-LYS443
ASP595-ARG437
GLU597-LYS312
ASP535-LYS575
GLU594-LYS311
ASP602-ARG605
ASP569-ARG528
GLU596-LYS311
GLU594-LYS311 ASP595-ARG437 GLU596-ARG4 GLU596-LYS311 ASP601-ARG604
ARG105.NH2-PHE181.O ARG131.NH2-ASP289.OD1 ARG131.N-THR135.O ARG298.NH2-ASP295.OD1 ARG310.N-GLN605.OE1 ARG310.NH1-GLU290.OE1 ARG310.NH2-GLU290.OE2
ALA210.N-ALA206.O ALA211.N-TRP207.O ALA234.N-PHE230.O ALA255.N-GLY251.O ALA313.N-VAL125.O ALA512.N-VAL508.O ALA516.N-ALA512.O
ARG131.NH1-ASP289.OD1
ARG131.NH2-ASP289.OD2
ARG188.NE-ASN51.OD1
ARG298.NH2-ASP295.OD2
ARG76.NH1-ASP92.OD1
ASN119.ND2-GLN19.OE1
ASN133.ND2-GLY195.O
ALA211.N-TRP207.O
ALA234.N-PHE230.O
ALA255.N-GLY251.O
ALA266.N-LEU262.O
ALA70.N-VAL73.O
ARG105.NH1-ASP176.OD2
GLY283.N-THR280.O
CYS128.N-PHE112.O
HIS172.N-ILE136.O
GLY146.N-HIS163.O
CYS117.N-SER147.OG
CYS300.N-VAL296.O
ASN274.ND2-GLU270.O ASN274.N-GLU270.O
ASN221.ND2-PHE223.O ASN231.ND2-LEU242.O
GLY120.N-ASN28.OD1
ASP92.N-ARG76.O
GLY29.N-VAL18.O
GLY109.N-MET130.O
ASN95.ND2-TRP31.O
HIS163.N-SER147.O
GLU290.N-GLU288.OE2
ASN95.ND2-GLY15.O
CYS22.N-THR25.O
GLU240.N-THR199.O
ASN95.N-ASP33.O
CYS265.N-VAL261.O
ASN238.ND2-ASP197.O
ASN214.ND2-ASP216.OD1
GLU178.N-ASP176.OD2
ASN65.N-SER62.O
ASN277.ND2-ASN274.O
ASN231.N-LEU227.O
ASN214.N-ALA210.O
ASN231.N-LEU227.O
ASN231.ND2-LEU242.O
ASN203.ND2-GLY109.O
ASN214.ND2-ASP216.OD2
ASN142.ND2-GLY608.O
ASN221.N-SER267.OG
ASN180.ND2-ASP176.OD1
ASN133.ND2-GLY195.O ASN203.ND2-ASP289.O
ASN151.ND2-THR111.O
ARG76.NH1-GLN74.OE1
ASN133.ND2-GLY195.O
ARG604.N-PHE600.O
GLN83.N-VAL86.O
ASN119.N-GLY143.O
ASN28.N-CYS145.O
ASN119.ND2-THR26.OG1
ARG604.NH1-ASP601.OD1
GLN69.N-GLN19.O
GLN83.NE2-GLU178.OE1
ASN231.N-LEU227.O
ASN274.N-GLU270.O
ARG60.NH2-ASP56.OD2
ARG585.NE-ASN583.O ARG604.NH1-MET312.O ARG604.NH2-SER123.O
ARG4.NH1-GLU596.OE1 ARG40.NH2-ASP187.OD1 ARG494.NH2-ASP354.O
ASP229.N-THR226.OG1
CYS16.N-VAL13.O
GLN189.N-MET49.O
ASN214.ND2-ALA210.O
ASN221.N-SER267.OG
ARG523.NH1-GLN612.O ARG523.NH2-GLN612.OXT
ARG366.N-ASP362.O ARG382.NH1-ASP398.OD1
ARG437.N-THR441.O ARG494.NH1-GLU361.OE2
ARG310.NH1-GLU290.OE2 ARG346.NH2-ASP493.OD1
ARG40.NH2-ASP187.OD1 ARG437.NH1-ASP595.OD1
ARG222.NE-GLU270.OE2 ARG298.NH2-MET6.O
ARG40.N-CYS85.O ARG40.NE-ASP187.OD2
ARG131.NE-ASP197.OD2 ARG188.NE-MET49.O
ASN231.ND2-LEU242.O
ASN65.N-SER62.O
ASP216.N-ALA211.O
ASN180.N-ASP176.OD1
ASN277.ND2-LEU272.O
ASN53.ND2-ASP56.OD1
ASN133.ND2-GLY195.O
ASN151.N-SER158.O
ASN203.ND2-GLY109.O
ASN231.N-LEU227.O
ASN274.N-GLU270.O
ARG40.NH2-ASP187.OD1
ARG60.NH2-ASP56.OD2
ASN214.ND2-ALA210.O
ASN231.ND2-LEU242.O
ARG40.N-CYS85.O
ARG366.NH1-ASP362.OD2 ARG382.NH2-ASP398.OD2
ALA70.N-VAL73.O ARG105.NH2-PHE181.O
ASN180.ND2-ASP176.OD1
ASN203.ND2-GLY109.O
ARG298.NH2-MET6.O
ARG298.N-PHE294.O
ARG40.NE-ASP187.OD2
ARG346.NE-ASP493.OD1 ARG346.NH2-ASP493.OD2 ARG366.NE-ASP362.OD1
ALA540.N-ASN537.O ALA572.N-LEU568.O ALA7.N-VAL431.O
ASN151.ND2-THR111.O
ASN151.N-SER158.O
ASN180.N-ASP176.OD1
ARG131.N-THR135.O
ARG217.NH2-GLN306.OXT
ARG105.NH2-PHE181.O
ALA479.N-MET471.O
ALA206.N-VAL202.O
ALA194.N-THR169.OG1
ALA210.N-ALA206.O
Dimer-N3 ALA173.N-MET165.O
ALA173.N-MET165.O
Dimer-apo ALA173.N-MET165.O
Monomer-N3
ALA173.N-MET165.O
Monomer-apo
ALA129.N-GLU290.OE1
Table 2.9 HBs of the optimized six models of [340] Dimer-2N3
ASN581.ND2-GLU577.O
ASN538.N-LEU534.O
ASN538.ND2-LEU549.O
ASN510.ND2-GLY416.O
ASN458.ND2-THR418.O
ASN440.ND2-GLY502.O
ASN370.ND2-VAL384.O
ASN335.ND2-CYS452.O
ASN335.N-CYS452.O
ASN274.N-GLU270.O
ASN238.ND2-ASP197.O
ASN231.ND2-LEU242.O
ASN221.ND2-ALA266.O
ASN214.ND2-ASP216.OD2
ASN180.ND2-GLY179.O
ARG524.NH1-GLN613.OE1
ARG438.N-THR442.O
ARG438.NH1-ASP596.OD1
ARG438.NE-ASP504.OD1
ARG412.NH2-PHE488.O
ARG4.NH2-GLU597.OE2
ARG4.NH1-GLU597.OE1
ARG4.N-GLN299.OE1
ARG383.NE-ASP399.OD1
ARG367.NH2-ASP363.OD1
ARG367.NH1-ASP355.OD2
ARG367.NE-ASP363.OD2
ARG347.NH2-ASP494.OD1
ARG311.NH2-GLU290.OE2
ARG311.NH1-GLU290.OE1
ARG311.N-GLN606.OE1
ARG279.NH1-ASN277.O
ARG131.N-THR135.O
ARG131.NH2-ASP289.OD2
ARG131.NH1-ASP289.OD1
ALA480.N-MET472.O
ALA255.N-GLY251.O
ALA234.N-PHE230.O
Dimer-2N3-covalent
LYS443.NZ-ASP503.OD2
ASN214.ND2-ALA210.O
ALA255.N-GLY251.O
MET541.N-ASN537.O
ASN221.N-SER267.OG
PHE223.N-ASN221.OD1
LEU381.N-VAL374.O
TYR343.OH-GLU484.OE2
LYS394.NZ-GLU484.OE2
LEU336.N-TYR343.O
GLY335.N-VAL324.O
GLU484.N-ASP482.OD1
ASN425.ND2-GLN306.OE1
HIS469.N-SER453.O
PHE446.N-SER1.O
GLN256.NE2-CYS300.O
ARG222.NE-ASP263.OD2
LEU395.N-VAL342.O
TYR424.OH-ASN448.O
SER450.N-LEU447.O
HIS478.N-ILE442.O
ASN439.ND2-GLY501.O
ILE384.N-LYS396.O
LYS394.N-SER387.OG
LEU373.N-THR327.O
LEU473.N-VAL477.O
MET388.N-GLN389.OE1
ARG346.N-CYS391.O
ASN371.N-SER368.O
THR331.OG1-CYS350.O
ARG346.NH2-ASP493.OD1
GLN498.NE2-VAL492.O
GLU361.N-GLU361.OE2
ASN359.ND2-GLU361.OE2
THR351.N-ASP354.OD1
ASN359.N-ASN357.OD1
ARG366.NE-ASP362.OD1
ASN357.ND2-ASP362.OD2
78 2 3C-Like Protease (3CLpro)
TRP207.NE1-PHE3.O
TRP218.N-ASP216.OD1
TYR209.OH-ILE259.O
TYR237.N-ALA234.O
VAL18.N-GLY29.O
VAL20.N-LEU27.O
VAL35.N-LEU32.O
VAL91.N-ASP34.O
LEU268.N-MET264.O
LEU272.N-LEU268.O
LEU30.N-TYR37.O
LEU57.N-ASN53.O
LEU58.N-TYR54.O
LEU67.N-THR21.O
LEU75.N-VAL68.O
LEU87.N-CYS38.O
GLY149.N-TYR161.O GLY29.N-VAL18.O
GLN192.NE2-ALA193.O
GLY146.N-HIS163.O
CYS606.N-VAL602.O GLN19.N-GLN69.O
GLY11.N-GLU320.OE1
CYS571.N-VAL567.O
GLU546.N-THR505.O
CYS423.N-SER453.OG
GLY109.N-MET130.O
GLU353.N-GLU353.OE1
CYS38.N-LEU87.O CYS434.N-PHE418.O
GLU290.N-GLU288.OE1
CYS350.N-HIS347.O
GLU240.N-THR199.O
THR45.N-ASP48.OD2
LEU242.N-ASN231.OD1
CYS344.N-LEU393.O
THR292.N-ASP295.OD1
LEU208.N-VAL204.O GLN83.N-VAL86.O
GLN74.NE2-GLN69.OE1
CYS322.N-VAL319.O
THR25.OG1-CYS44.O
LEU205.N-THR201.O CYS328.N-THR331.O
GLN416.NE2-THR417.O GLN562.NE2-VAL609.O
CYS265.N-VAL261.O CYS300.N-VAL296.O
THR111.OG1-ASP295.OD1
THR21.N-LEU67.O
LEU141.N-TYR118.OH
LEU167.N-VAL171.O
GLN19.NE2-ASN119.O GLN244.NE2-ASP248.OD1 GLN389.N-VAL392.O
CYS117.N-SER147.OG CYS128.N-PHE112.O CYS156.N-ASP153.O
MET235.N-ASN231.O
SER254.N-LEU250.O
SER62.N-ASN65.OD1
ILE136.N-HIS172.O
LEU115.N-VAL148.O
ILE106.N-TYR182.OH
CYS434.N-PHE418.O GLN107.NE2-GLN110.OE1
ASP56.N-ASN53.OD1 ASP92.N-ARG76.O
MET162.N-THR175.O
MET165.N-ALA173.O
HIS164.N-ALA173.O
HIS80.ND1-ASN63.OD1
CYS322.N-VAL319.O CYS423.N-SER453.OG
ASN95.ND2-GLY15.O ASN95.ND2-TRP31.O
LYS5.NZ-GLU288.OE2
LYS90.NZ-ASP34.CG
GLY29.N-VAL18.O
HIS163.N-SER147.O
CYS156.N-ASP153.O CYS16.N-VAL13.O
ASN580.N-GLU576.O ASN95.N-ASP33.O
LYS12.NZ-ASP155.OD1
LYS269.NZ-THR225.OG1
GLY149.N-TYR161.O
GLY15.N-GLY11.O
ASP354.N-THR351.O CYS128.N-PHE112.O
ASN537.N-LEU533.O ASN580.ND2-GLY581.O
LYS102.N-VAL157.O
LYS102.NZ-PHE103.O
GLY120.N-ASN28.OD1
ASN65.N-SER62.O ASP153.N-CYS156.O
ASN520.ND2-ALA516.O ASN537.ND2-LEU548.O
GLY146.N-HIS163.O
LYS100.N-ASP155.OD2
LYS100.NZ-TYR101.O
GLU290.N-GLU288.OE2
GLY109.N-MET130.O
HIS172.N-ILE136.O
GLY565.N-SER561.O
GLY486.N-ASP483.OD1
GLY456.N-TYR468.O
GLY416.N-MET437.O
GLY336.N-VAL325.O
GLY318.N-GLU14.OE1
GLY29.N-VAL18.O
GLY215.N-ALA211.O
GLY149.N-TYR161.O
GLY146.N-HIS163.O
GLY120.N-ASN28.OD1
GLY109.N-MET130.O
GLU547.N-THR506.O
GLU290.N-GLU288.OE1
GLN83.N-VAL86.O
GLN69.N-GLN19.O
GLN613.NE2-THR564.O
GLN563.NE2-VAL610.O
GLN563.NE2-CYS607.O
GLN551.NE2-ASP555.OD1
GLN499.NE2-VAL493.O
GLN496.N-MET356.O
GLN417.NE2-THR418.O
GLN376.NE2-GLY378.O
GLN299.NE2-ASP295.O
GLN19.NE2-THR26.OG1
GLN189.N-MET49.O
GLN107.N-GLN110.OE1
ASN53.ND2-ASP56.OD1 ASN537.ND2-LEU548.O ASN63.ND2-ILE78.O
ASN457.N-SER464.O ASN509.ND2-ASP595.O ASN509.ND2-GLY415.O
LEU32.N-VAL35.O
LEU87.N-CYS38.O
LEU89.N-VAL36.O
GLU14.N-SER10.O
GLU240.N-THR199.O
GLN273.N-LYS269.O
CYS435.N-PHE419.O CYS607.N-VAL603.O
ASN509.ND2-GLY415.O
CYS424.N-SER454.OG
CYS160.N-GLY149.O
ASP460.N-CYS463.O
ASN95.ND2-TRP31.O
ASN95.ND2-GLY15.O
ASN65.N-SER62.O
ASN527.N-SER573.OG
ASN401.ND2-TRP337.O ASN439.ND2-GLY501.O
LEU27.N-VAL20.O
LEU30.N-TYR37.O
GLN192.NE2-VAL186.O
ASN486.ND2-ARG411.NH2
GLN256.NE2-VAL303.O
ASN457.N-SER464.O
ASN390.ND2-GLY485.O ASN401.ND2-GLY321.O
LEU141.N-TYR118.OH
LEU167.N-VAL171.O
GLN189.N-MET49.O
ASN439.ND2-GLY501.O
ASN371.N-SER368.O
ILE78.N-LYS90.O
GLN127.NE2-ASP295.OD1
GLN19.N-GLN69.O
ASN390.ND2-GLY485.O
ASN334.ND2-CYS451.O
ILE43.N-ARG40.O
GLN107.N-GLN110.OE1
ASN334.ND2-CYS451.O
ASN28.ND2-CYS145.O
ILE213.N-TYR209.O
ASN28.ND2-CYS145.O
ASN274.ND2-GLU270.O
ILE136.N-HIS172.O
CYS44.N-HIS41.O
CYS85.N-GLY179.O
PHE8.N-SER113.OG
(continued)
THR598.N-ASP601.OD1
TRP513.N-ASN509.O
LYS5.NZ-GLU288.OE1
LYS575.N-CYS571.O
ASN231.N-LEU227.O
ARG585.NH2-ASN580.OD1
VAL233.N-PHE230.O
LYS408.NZ-ASP459.OD2
ARG298.NH2-ASP295.OD1
GLN550.NE2-ASP551.OD1
ASP295.N-THR292.O
GLU596.N-GLU594.OE1
THR532.N-ASP535.OD2
GLY584.N-ALA285.O
ASN228.ND2-ASP229.OD1
ARG298.NH1-SER429.O
GLN299.NE2-ARG4.O
LEU593.N-GLY283.O
LEU268.N-MET264.O
THR226.N-ASP229.OD2
ASN401.ND2-TRP337.O
SER427.OG-PHE305.O
CYS466.N-GLY455.O
SER429.N-ALA422.O
GLY415.N-MET436.O
ARG4.NH2-GLU596.OE2
SER445.OG-GLN299.OE1
ARG437.NH1-ASP595.OD2
ASN537.ND2-LEU548.O
ALA376.N-VAL379.O
TRP337.N-CYS322.O
GLY426.N-ASN334.OD1
GLY455.N-TYR467.O
TYR424.N-SER427.O
SER445.N-TYR432.OH
CYS300.N-VAL296.O
2.4 Concluding Remarks 79
GLN299.NE2-ARG4.O GLN325.N-GLN375.O GLN375.NE2-ASN378.O GLN375.N-GLN325.O GLN389.NE2-LEU483.O GLN413.N-GLN416.OE1
LYS102.N-VAL157.O
LYS236.N-LEU232.O
LYS88.N-SER81.O
MET165.N-ALA173.O
MET17.N-GLU14.O
MET235.N-ASN231.O
Dimer-apo GLN256.N-PRO252.O
Monomer-N3
LEU89.N-VAL36.O
Monomer-apo
Table 2.9 (continued)
HIS172.N-ILE136.O
HIS164.ND1-MET162.O
HIS163.N-SER147.O
GLY455.N-TYR467.O
GLY452.N-HIS469.O
GLY415.N-MET436.O
GLY335.N-VAL324.O
Dimer-N3
LEU242.N-ASN231.OD1
ILE78.N-LYS90.O
ILE556.N-ASP552.O
ILE507.N-ASP596.OD2
ILE200.N-ASP289.OD2
HIS80.ND1-ASN63.OD1
HIS371.ND1-SER369.OG
Dimer-2N3
ARG131.NH1-ASP289.OD1
VAL463.N-LYS406.O
LYS100.NZ-ASP155.OD2
SER316.N-SER10.OG
LYS12.NZ-ASP155.O
CYS156.N-ASP153.O
PHE314.N-SER419.OG
Dimer-2N3-covalent
80 2 3C-Like Protease (3CLpro)
LYS88.N-SER81.O LYS90.N-GLY79.O MET165.N-ALA173.O MET471.N-ALA479.O PHE223.N-ASN221.OD1 PHE305.N-GLY302.O PHE440.N-ARG437.O PHE529.N-ASN527.OD1 PHE611.N-GLN562.O PHE66.N-ASN63.O SER284.N-ILE281.O SER368.N-ASN371.OD1
HIS163.N-SER147.O HIS469.N-SER453.O HIS478.N-ILE442.O HIS80.ND1-ASN63.OD1 ILE136.N-HIS172.O ILE249.N-ASP245.O ILE384.N-LYS396.O ILE412.N-TYR488.OH ILE442.N-HIS478.O ILE78.N-LYS90.O LEU115.N-VAL148.O LEU167.N-VAL171.O
TYR126.OH-LYS137.O
TYR161.OH-PHE134.O
TYR182.N-GLY174.O
TYR182.OH-CYS160.O
TYR209.N-LEU205.O
TYR209.OH-ILE259.O
TYR239.N-ALA234.O
TYR37.N-LEU30.O
VAL104.N-PHE159.O
VAL114.N-TYR126.O
VAL157.N-LYS100.O
LYS102.NZ-ASP153.OD2
GLY415.N-MET436.O
THR25.N-CYS22.O
TYR118.N-SER121.O
LEU89.N-VAL36.O
GLY335.N-VAL324.O
THR21.OG1-THR26.OG1
LYS575.NZ-ASP535.OD2
LEU574.N-MET570.O
GLY29.N-VAL18.O
THR21.N-LEU67.O
GLY608.N-GLN605.O
LEU473.N-VAL477.O
GLY275.N-LEU271.O
THR111.OG1-ASP295.OD2
TYR101.OH-ASP33.OD2
LEU395.N-VAL342.O
GLY149.N-TYR161.O
SER81.N-LYS88.O
LYS443.NZ-GLY283.O
LEU381.N-VAL374.O
GLY146.N-HIS163.O
SER62.N-ASN65.OD1
GLY521.N-VAL518.O
LEU363.N-ASN359.O
GLY120.N-ASN28.OD1
SER267.N-ASP263.O
TRP31.N-CYS16.O
LEU32.N-VAL35.O
GLY11.N-GLU320.OE1
SER254.N-LEU250.O
LYS406.NZ-ASP461.OD1
LEU282.N-ASP216.OD1
GLU596.N-GLU594.OE1
SER158.N-ASN151.O
GLY455.N-TYR467.O
LEU27.N-VAL20.O
GLU320.N-SER316.O
SER147.OG-SER144.O
TRP218.NE1-THR280.O
LEU268.N-MET264.O
GLU290.N-GLU288.OE2
SER123.N-ALA116.O
LYS269.NZ-GLU270.OE2
LEU167.N-VAL171.O
GLU270.N-ALA266.O
LYS394.N-SER387.O
ILE506.N-ASP595.OD2
GLU240.N-THR199.O
PHE8.N-SER113.OG
SER113.OG-GLN127.OE1
GLY426.N-ASN334.OD1
ILE384.N-LYS396.O
GLU14.N-SER10.O
PHE230.N-THR226.O
GLY452.N-HIS469.O
ILE249.N-ASP245.O
GLN83.N-VAL86.O
PHE223.N-ASN221.OD1
TRP207.N-ASN203.O
HIS478.N-ILE442.O
GLN69.N-GLN19.O
THR25.OG1-CYS44.O
HIS470.N-ALA479.O
GLN579.NE2-GLU576.OE1
PHE150.N-SER113.O
HIS386.ND1-ASN369.OD1
Dimer-N3
PHE112.N-CYS128.O
Dimer-apo GLN498.NE2-VAL492.O
Monomer-N3
MET264.N-ALA260.O
Monomer-apo
Table 2.10 HBs of the optimized six models of [340] (continuation 1)
SER1.OG-GLU473.OE2
PHE530.N-ASN528.OD1
PHE466.N-LYS409.O
PHE441.N-ARG438.O
PHE230.N-THR226.O
PHE140.N-SER308.O
PHE134.N-ARG131.O
MET437.N-GLN417.O
MET235.N-ASN231.O
LYS90.NZ-ASP34.OD1
LYS90.N-GLY79.O
LYS88.NZ-GLU178.OE1
LYS88.N-SER81.O
LYS576.N-CYS572.O
LYS543.N-VAL540.O
LYS5.NZ-GLU290.OE1
LYS444.NZ-ASP504.OD2
LYS395.NZ-GLN390.OE1
LYS395.N-SER388.O
LYS236.NZ-LEU232.O
LYS137.NZ-ASP197.OD1
LYS102.NZ-ASP153.OD2
LYS100.NZ-ASP155.OD1
LEU75.N-VAL68.O
LEU589.N-ASP523.OD2
LEU578.N-SER574.O
LEU575.N-MET571.O
LEU512.N-THR508.O
LEU396.N-VAL343.O
LEU394.N-CYS345.O
LEU365.N-TYR361.O
LEU337.N-TYR344.O
LEU334.N-VAL327.O
LEU282.N-ASP216.OD1
LEU268.N-MET264.O
Dimer-2N3
Dimer-2N3-covalent
GLY179.N-ASP176.O
ASN180.N-ASP176.OD2
TYR182.N-GLY174.O
ARG105.NH2-PHE181.O
ALA173.N-MET165.O
LEU167.N-VAL171.O
SER121.N-TYR118.O
GLY120.N-ASN28.OD1
HIS163.N-SER147.O
ASN133.ND2-GLY195.O
(continued)
TYR101.OH-ASP33.OD1
ILE106.N-TYR182.OH
ARG131.N-THR135.O
PHE134.N-ARG131.O
GLY521.N-ALA517.O
SER123.N-ALA116.O
CYS160.N-GLY149.O
GLN107.N-GLN110.OE1
GLY109.N-MET130.O
ARG131.NE-ASP197.OD2
ASN238.ND2-ASP197.O
CYS128.N-PHE112.O
ALA516.N-ALA512.O
ARG310.NH2-GLU290.OE2
TYR515.OH-ILE565.O
LYS137.NZ-GLY589.O
LEU588.N-ASP522.OD1
ARG131.NH2-ASP197.OD1
TRP524.NE1-THR586.O
GLU240.N-THR199.O
THR199.N-ASN238.O
SER158.N-ASN151.O
ASN151.ND2-THR111.O
ASN203.ND2-ASP289.O
ASN203.ND2-GLY109.O
2.4 Concluding Remarks 81
THR21.N-LEU67.O THR332.OG1-CYS351.O THR352.N-ASP355.OD1 THR405.OG1-ASP340.OD1 THR45.N-ASP48.OD1 THR533.N-ASP536.OD1 THR98.OG1-ASP33.OD1 TRP218.NE1-THR280.O TRP338.N-CYS323.O TRP514.N-ASN510.O TYR101.OH-ASP33.OD2 TYR182.N-GLY174.O TYR209.OH-ILE259.O TYR344.N-LEU337.O TYR489.N-GLY481.O TYR54.OH-ASP187.O
THR98.OG1-ASP33.OD2 TRP31.N-CYS16.O TRP337.N-CYS322.O TRP524.NE1-THR586.O TYR118.N-SER121.O TYR118.OH-ARG604.O TYR182.N-GLY174.O TYR209.OH-ILE259.O TYR239.N-ALA234.O TYR488.N-GLY480.O TYR488.OH-CYS466.O VAL18.N-GLY29.O VAL20.N-LEU27.O VAL324.N-GLY335.O VAL342.N-LEU395.O VAL36.N-LEU89.O
LEU250.N-HIS246.O
LEU268.N-MET264.O
LEU27.N-VAL20.O
LEU272.N-LEU268.O
LEU282.N-ASP216.OD2
LEU30.N-TYR37.O
LEU32.N-VAL35.O
LEU333.N-VAL326.O
LEU336.N-TYR343.O
LEU338.N-VAL341.O
LEU364.N-TYR360.O
LEU373.N-THR327.O
LEU381.N-VAL374.O
LEU393.N-CYS344.O
LEU395.N-VAL342.O
LEU421.N-VAL454.O
LEU447.N-SER450.OG
LEU511.N-THR507.O
LEU514.N-VAL510.O
VAL297.N-PRO293.O
VAL35.N-LEU32.O
VAL36.N-LEU89.O
VAL91.N-ASP34.O
THR598.N-ASP601.OD2
THR531.N-LEU568.O
THR404.OG1-ASP339.OD1
THR292.N-ASP295.OD2
THR199.N-ASN238.O
SER446.N-TYR433.OH
SER420.OG-GLN434.OE1
SER301.N-GLN306.OXT
SER284.N-ILE281.O
LEU232.N-ASN228.O
THR25.OG1-CYS44.O
VAL212.N-LEU208.O
SER139.OG-GLN606.OE1
THR199.N-ASN238.O
LEU208.N-VAL204.O
Dimer-2N3
Dimer-N3
VAL20.N-LEU27.O
Dimer-apo
LEU205.N-THR201.O
Monomer-N3
VAL18.N-GLY29.O
Monomer-apo
Table 2.10 (continued)
ARG60.NH2-ASP56.OD1
ASN51.N-ASP48.O
ASN65.N-SER62.O
THR45.N-ASP48.OD1
ARG188.NH1-GLU55.OE1
GLN189.NE2-MET49.O
GLN189.NE2-TYR54.OH
TYR54.OH-ASP187.O
ARG188.NH1-ASP187.OD2
ARG40.NH2-ASP187.OD1
ASN63.ND2-VAL77.O
GLN192.NE2-THR190.O
GLN192.NE2-VAL186.O
LYS88.N-SER81.O
GLN83.N-VAL86.O
CYS85.N-GLY179.O
VAL91.N-ASP34.O
GLN19.NE2-THR26.OG1
LEU27.N-VAL20.O
VAL20.N-LEU27.O
GLY29.N-VAL18.O
GLN83.NE2-GLU178.OE2
Dimer-2N3-covalent
82 2 3C-Like Protease (3CLpro)
VAL20.N-LEU27.O
VAL68.N-LEU75.O
VAL411.N-PHE466.O VAL464.N-LYS407.O
LEU592.N-SER590.OG
LEU67.N-THR21.O
LYS90.N-GLY79.O
LYS88.N-SER81.O
LYS61.N-LEU58.O
LYS575.N-CYS571.O
LYS5.NZ-GLU290.OE2
LYS443.NZ-ASP503.OD2
LYS406.NZ-ASP461.OD2
LYS403.N-ASN401.OD1
LYS396.N-GLY385.O
LYS394.NZ-GLN389.OE1
LYS394.N-SER387.O
LYS269.NZ-THR225.OG1
LYS269.N-CYS265.O
LYS102.N-VAL157.O
LEU89.N-VAL36.O
LEU75.N-VAL68.O
VAL327.N-LEU334.O VAL398.N-ASP341.O
LEU578.N-LEU574.O
LEU588.N-ASP522.OD2
VAL247.N-GLN244.O VAL320.N-SER317.O
LEU57.N-ASN53.O
LEU574.N-MET570.O
LEU577.N-SER573.O
VAL104.N-PHE159.O VAL18.N-GLY29.O
VAL397.N-ASP340.O VAL603.N-PRO599.O
LEU538.N-ASN534.O
LEU548.N-ASN537.OD1
ARG60.NE-ASP56.OD2
2.4 Concluding Remarks 83
84
2 3C-Like Protease (3CLpro)
Table 2.11 HBs of the optimized six models of [340] (continuation 2) Monomer-apo
Monomer-N3
Dimer-apo
Dimer-N3
Dimer-2N3
Dimer-2N3-covalent
LYS97.N-ASN95.OD1 LYS97.NZ-ASN95.OD1 MET162.N-THR175.O MET165.N-ALA173.O MET235.N-ASN231.O MET264.N-ALA260.O MET355.N-THR351.O MET468.N-THR481.O PHE112.N-CYS128.O PHE150.N-SER113.O PHE309.N-LEU588.O PHE314.N-SER419.OG PHE418.N-CYS434.O PHE456.N-SER419.O PHE536.N-THR532.O PHE8.N-SER113.OG SER10.OG-GLU14.OE1 SER113.OG-GLN127.OE1 SER139.N-TYR126.OH SER147.N-SER144.O SER158.N-ASN151.O SER254.N-LEU250.O SER254.OG-ILE259.O SER267.N-ASP263.O SER307.OG-GLU166.OE1 SER387.N-LYS394.O SER387.OG-HIS386.O SER419.OG-GLN433.OE1 SER445.N-TYR432.OH SER450.N-LEU447.O SER573.N-ASP569.O SER607.N-VAL603.O THR111.OG1-ASP295.OD2 THR175.N-MET162.O THR190.OG1-GLN189.O THR21.N-LEU67.O THR257.OG1-LEU253.O THR327.N-LEU373.O THR331.N-CYS328.O THR404.OG1-ASN401.O THR481.N-MET468.O THR481.OG1-ASN486.O THR507.OG1-GLU546.O THR532.N-ASP535.OD1 TRP207.N-ASN203.O TRP218.NE1-THR280.O TRP31.N-CYS16.O TRP513.N-ASN509.O TRP524.NE1-THR586.O TYR118.N-SER121.O TYR182.N-GLY174.O TYR182.OH-CYS160.O TYR209.N-LEU205.O TYR209.OH-ILE259.O TYR239.N-ALA234.O TYR343.N-LEU336.O TYR37.N-LEU30.O TYR407.OH-ASP339.OD2 TYR424.N-SER427.O
(continued)
2.4 Concluding Remarks
85
Table 2.11 (continued) Monomer-apo
Monomer-N3
Dimer-apo
Dimer-N3
Dimer-2N3
Dimer-2N3-covalent
TYR432.N-VAL420.O TYR488.N-GLY480.O TYR488.OH-CYS466.O TYR515.N-LEU511.O TYR515.OH-ILE565.O VAL114.N-TYR126.O VAL125.N-ALA313.O VAL157.N-LYS100.O VAL18.N-GLY29.O VAL20.N-LEU27.O VAL204.N-ILE200.O VAL324.N-GLY335.O VAL326.N-LEU333.O VAL341.N-LEU338.O VAL342.N-LEU395.O VAL36.N-LEU89.O VAL392.N-GLN389.O VAL397.N-ASP340.O VAL410.N-PHE465.O VAL420.N-TYR432.O VAL431.N-ALA7.O VAL463.N-LYS406.O VAL492.N-GLN498.OE1 VAL91.N-ASP34.O
Table 2.12 SBs of MDs of the monomer-apo model of [340] rep1
rep2
rep3
rep4
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP155-LYS100
rep5
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS12
ASP155-LYS12
ASP155-LYS102
ASP155-LYS12
ASP155-LYS12
ASP176-ARG105
ASP176-ARG105
ASP155-LYS12
ASP176-ARG105
ASP176-ARG105
ASP187-ARG188
ASP187-ARG188
ASP176-ARG105
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP197-ARG131
ASP197-ARG131
ASP187-ARG40
ASP197-ARG131
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP216-ARG279
ASP216-ARG279
ASP197-LYS137
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP229-LYS269
ASP216-ARG279
ASP229-LYS269
ASP229-ARG222
ASP263-ARG222
ASP263-ARG222
ASP229-LYS269
ASP263-ARG222
ASP229-LYS269
ASP289-ARG131
ASP289-ARG131
ASP263-ARG222
ASP289-ARG131
ASP263-ARG222
ASP289-LYS137
ASP289-LYS137
ASP289-ARG131
ASP289-LYS137
ASP289-ARG131
ASP295-ARG298
ASP295-ARG298
ASP289-LYS137
ASP295-ARG298
ASP289-LYS137
ASP34-LYS90
ASP295-ARG4
ASP295-ARG298
ASP34-LYS90
ASP295-ARG298
ASP48-ARG60
ASP34-LYS90
ASP34-LYS90
ASP48-ARG60
ASP34-LYS90
ASP48-LYS61
ASP48-ARG60
ASP48-ARG60
ASP48-LYS61
ASP48-ARG60
ASP56-ARG60
ASP48-LYS61
ASP48-LYS61
ASP56-ARG60
ASP48-LYS61
ASP92-ARG76
ASP56-ARG60
ASP56-ARG60
ASP92-ARG76
ASP56-ARG60
GLU14-LYS97
ASP92-ARG76
ASP92-ARG76
GLU178-ARG105
ASP92-ARG76
GLU178-ARG105
GLU14-LYS97
GLU178-ARG105
GLU178-LYS88
GLU178-ARG105
GLU178-LYS88
GLU178-ARG105
GLU178-LYS88
GLU270-ARG222
GLU270-ARG222
GLU270-LYS269
GLU178-LYS88
GLU270-ARG279
GLU270-LYS269
GLU270-LYS269
GLU288-LYS137
GLU270-ARG222
GLU270-LYS269
GLU288-LYS137
GLU288-LYS137
GLU288-LYS5
GLU270-LYS269
GLU288-LYS137
GLU288-LYS5
GLU288-LYS5
GLU290-ARG131
GLU288-ARG4
GLU288-LYS5
GLU290-ARG131
GLU290-ARG131
GLU290-LYS137
GLU288-LYS137
GLU290-ARG131
GLU290-LYS137
GLU290-LYS137
GLU290-LYS5
GLU288-LYS5
GLU290-LYS137
GLU290-LYS5
GLU290-LYS5
GLU55-ARG40
GLU290-ARG131
GLU290-LYS5
GLU47-LYS61
GLU290-LYS137
GLU47-ARG188
GLU55-ARG188
GLU290-LYS5
GLU55-ARG188
GLU55-ARG40
GLU55-ARG188
GLU55-ARG40
GLU55-ARG40
86
2 3C-Like Protease (3CLpro)
Table 2.13 SBs of MDs of the monomer-N3 model of [340] rep1
rep2
rep3
rep4
ASP153-LYS102
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP155-LYS100
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
rep5
ASP155-LYS102
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS12
ASP155-LYS102
ASP155-LYS102
ASP155-LYS102
ASP155-LYS12
ASP176-ARG105
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP176-ARG105
ASP187-ARG188
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP187-ARG188
ASP187-ARG40
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP197-ARG131
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP197-ARG131
ASP197-LYS137
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-LYS137
ASP216-ARG279
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP216-ARG279
ASP229-LYS269
ASP216-ARG279
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP263-ARG222
ASP229-LYS269
ASP229-LYS269
ASP229-LYS269
ASP263-ARG222
ASP289-ARG131
ASP263-ARG222
ASP263-ARG222
ASP263-ARG222
ASP289-ARG131
ASP295-ARG298
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP289-LYS137
ASP34-LYS90
ASP295-ARG298
ASP289-LYS137
ASP289-LYS137
ASP295-ARG298
ASP48-ARG60
ASP34-LYS90
ASP295-ARG298
ASP295-ARG298
ASP34-LYS90
ASP295-ARG4
ASP48-ARG60
ASP48-LYS61
ASP48-ARG60
ASP295-LYS5
ASP56-ARG60
ASP48-LYS61
ASP34-LYS90
ASP34-LYS90
ASP48-LYS61
ASP92-ARG76
ASP56-ARG60
ASP48-ARG60
ASP48-ARG60
ASP56-ARG60
GLU178-ARG105
ASP92-ARG76
ASP48-LYS61
ASP48-LYS61
ASP92-ARG76
GLU178-LYS88
GLU178-ARG105
ASP56-ARG60
ASP56-ARG60
GLU178-ARG105
GLU270-ARG222
GLU270-ARG222
ASP92-ARG76
ASP92-ARG76
GLU178-LYS88
GLU270-LYS269
GLU270-LYS269
GLU178-ARG105
GLU14-LYS97
GLU270-ARG279
GLU288-ARG4
GLU288-LYS5
GLU178-LYS88
GLU178-ARG105
GLU270-LYS269
GLU288-LYS137
GLU290-ARG131
GLU270-ARG222
GLU178-LYS88
GLU288-ARG4 GLU288-LYS137
GLU288-LYS5
GLU290-LYS137
GLU270-LYS269
GLU270-ARG222
GLU290-ARG131
GLU290-LYS5
GLU288-ARG4
GLU270-LYS269
GLU288-LYS5
GLU290-LYS137
GLU55-ARG40
GLU288-LYS137
GLU288-LYS137
GLU290-ARG131
GLU288-LYS5
GLU288-LYS5
GLU290-LYS5
GLU290-LYS137
GLU55-ARG188
GLU290-ARG131
GLU290-ARG131
GLU290-LYS5
GLU55-ARG40
GLU290-ARG4
GLU290-LYS137
GLU55-ARG40
GLU290-LYS137
GLU290-LYS5
GLU290-LYS5
GLU55-ARG40
GLU55-ARG40
2.4 Concluding Remarks
87
Table 2.14 SBs of MDs of the dimer-apo model of [340] rep1
rep2
rep3
rep4
rep5
ASP153-LYS102
ASP153-LYS102
ASP153-ARG298
ASP153-ARG298
ASP153-LYS102
ASP155-LYS100
ASP155-LYS100
ASP153-LYS102
ASP153-LYS102
ASP155-LYS100
ASP155-LYS12
ASP155-LYS12
ASP155-LYS100
ASP155-LYS100
ASP155-LYS12
ASP176-ARG105
ASP176-ARG105
ASP155-LYS12
ASP155-LYS12
ASP176-ARG105
ASP187-ARG188
ASP187-ARG188
ASP176-ARG105
ASP176-ARG105
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP197-ARG131
ASP197-ARG131
ASP187-ARG40
ASP187-ARG40
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP197-ARG131
ASP197-ARG131
ASP197-LYS137
ASP216-ARG217
ASP216-ARG279
ASP197-LYS137
ASP197-LYS137
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP229-LYS269
ASP263-ARG222
ASP229-LYS269
ASP229-LYS269
ASP263-ARG222
ASP263-ARG222
ASP289-ARG131
ASP263-ARG222
ASP263-ARG222
ASP289-ARG131
ASP289-ARG131
ASP295-ARG298
ASP289-ARG131
ASP289-ARG131
ASP295-ARG298
ASP295-ARG298
ASP340-LYS396
ASP289-LYS137
ASP295-ARG298
ASP340-LYS396
ASP340-LYS396
ASP34-LYS90
ASP295-ARG298
ASP340-LYS396
ASP34-LYS90
ASP34-LYS90
ASP354-ARG366
ASP295-LYS5
ASP34-LYS90
ASP354-ARG366
ASP354-ARG366
ASP354-LYS367
ASP340-LYS396
ASP354-ARG366
ASP354-LYS367
ASP354-LYS367
ASP362-ARG366
ASP34-LYS90
ASP354-LYS367
ASP362-ARG366
ASP362-ARG366
ASP398-ARG382
ASP354-ARG366
ASP362-ARG366
ASP398-ARG382
ASP398-ARG382
ASP459-LYS408
ASP354-LYS367
ASP362-LYS367
ASP459-LYS408
ASP459-LYS408
ASP461-LYS318
ASP362-ARG366
ASP398-ARG382
ASP461-LYS318
ASP461-LYS318
ASP461-LYS406
ASP398-ARG382
ASP459-ARG604
ASP461-LYS406
ASP461-LYS406
ASP482-ARG411
ASP459-LYS408
ASP459-LYS408
ASP482-ARG411
ASP482-ARG411
ASP48-ARG60
ASP461-LYS318
ASP461-LYS318
ASP48-ARG60
ASP48-ARG60
ASP48-LYS61
ASP461-LYS406
ASP461-LYS406
ASP493-ARG346
ASP48-LYS61
ASP493-ARG346
ASP482-ARG411
ASP461-LYS408
ASP493-ARG494
ASP493-ARG346
ASP493-ARG494
ASP48-ARG60
ASP482-ARG411
ASP503-ARG437
ASP493-ARG494
ASP503-ARG437
ASP48-LYS61
ASP48-ARG60
ASP503-LYS443
ASP503-ARG437
ASP503-LYS443
ASP493-ARG346
ASP48-LYS61
ASP522-ARG585
ASP503-LYS443
ASP522-ARG585
ASP493-ARG494
ASP493-ARG346
ASP535-LYS575
ASP522-ARG585
ASP535-LYS575
ASP503-ARG437
ASP493-ARG494
ASP569-ARG528
ASP535-LYS575
ASP569-ARG528
ASP503-LYS443
ASP503-ARG437
ASP56-ARG60
ASP569-ARG528
ASP56-ARG60
ASP522-ARG585
ASP503-LYS443
ASP595-ARG437
ASP56-ARG60
ASP595-ARG437
ASP535-LYS575
ASP522-ARG585
ASP601-ARG604
ASP595-ARG437
ASP601-ARG604
ASP569-ARG528
ASP535-LYS575
ASP92-ARG76
ASP601-ARG604
ASP601-LYS311
ASP56-ARG60
ASP569-ARG528
GLU178-ARG105
ASP92-ARG76
ASP92-ARG76
ASP595-ARG437
ASP56-ARG60
GLU178-LYS88
GLU178-ARG105
GLU14-LYS318
ASP601-ARG604
ASP595-ARG437
GLU270-ARG222
GLU178-LYS88
GLU178-ARG105
ASP92-ARG76
ASP601-ARG604
GLU270-LYS269
GLU270-ARG222
GLU178-LYS88
GLU178-ARG105
ASP92-ARG76
GLU288-LYS5
GLU270-LYS269
GLU270-LYS269
GLU178-LYS88
GLU178-ARG105
GLU290-ARG131
GLU288-LYS5
GLU288-LYS5
GLU270-ARG222
GLU178-LYS88
GLU290-ARG310
GLU290-ARG131
GLU290-ARG131
GLU270-ARG279
GLU270-ARG222
GLU290-LYS137
GLU290-ARG310
GLU290-ARG310
GLU270-LYS269
GLU270-ARG279
GLU290-LYS5
GLU290-LYS5
GLU290-LYS5
GLU288-LYS137
GLU270-LYS269
GLU353-LYS367
GLU361-ARG346
GLU320-LYS12
GLU288-LYS5
GLU288-LYS5
GLU361-ARG346
GLU484-ARG411
GLU353-ARG366
GLU290-ARG310
GLU290-ARG131
GLU484-ARG411
GLU576-ARG528
GLU353-LYS367
GLU290-LYS137
GLU290-ARG310
GLU484-LYS394
GLU576-LYS575
GLU361-ARG346
GLU290-LYS5
GLU290-LYS5
GLU55-ARG188
GLU594-LYS311
GLU361-ARG494
GLU320-LYS12
GLU320-LYS12
GLU55-ARG40
GLU594-LYS443
GLU47-ARG60
GLU353-LYS367
GLU353-ARG366
GLU576-ARG528
GLU596-ARG4
GLU47-LYS61
GLU361-ARG346
GLU361-ARG346
GLU576-ARG585
GLU596-ARG437
GLU484-ARG411
GLU47-LYS61
GLU361-ARG366
GLU576-LYS575
GLU596-LYS311
GLU484-LYS394
GLU484-ARG411
GLU47-LYS61
GLU594-LYS311
GLU55-ARG188
GLU484-LYS394
GLU484-ARG411
GLU596-ARG4
GLU576-ARG528
GLU576-ARG528
GLU484-LYS394
GLU596-ARG437
GLU576-LYS575
GLU576-LYS575
GLU55-ARG188
GLU596-LYS311
GLU594-LYS311
GLU594-ARG4
GLU576-ARG528
GLU596-LYS443
GLU594-LYS443
GLU594-LYS311
GLU576-LYS575
GLU596-ARG4
GLU594-LYS443
GLU594-LYS311
GLU596-ARG437
GLU594-LYS5
GLU596-ARG4
GLU596-LYS311
GLU596-ARG4
GLU596-ARG437
GLU596-LYS443
GLU596-ARG437
GLU596-LYS311
GLU596-LYS311
GLU596-LYS443
88
2 3C-Like Protease (3CLpro)
Table 2.15 SBs of MDs of the dimer-N3 model of [340] rep1
rep2
rep3
rep4
rep5
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-LYS102
ASP153-ARG298
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP155-LYS100
ASP153-LYS102
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS102
ASP155-LYS100
ASP155-LYS12
ASP155-LYS102
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP176-ARG105
ASP155-LYS12
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP187-ARG188
ASP176-ARG105
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP197-ARG131
ASP187-ARG40
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-LYS137
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP216-ARG279
ASP197-LYS137
ASP216-ARG279
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP216-ARG279
ASP229-LYS269
ASP229-LYS269
ASP229-LYS269
ASP263-ARG222
ASP229-LYS269
ASP263-ARG222
ASP263-ARG222
ASP263-ARG222
ASP289-ARG131
ASP263-ARG222
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP295-ARG298
ASP289-ARG131
ASP289-LYS137
ASP295-ARG298
ASP295-ARG298
ASP340-LYS396
ASP295-ARG298
ASP295-ARG298
ASP340-LYS396
ASP340-LYS396
ASP34-LYS90
ASP340-LYS396
ASP340-LYS396
ASP34-LYS90
ASP34-LYS90
ASP354-ARG366
ASP34-LYS90
ASP34-LYS90
ASP354-ARG366
ASP354-ARG366
ASP354-LYS367
ASP354-ARG366
ASP354-ARG366
ASP354-LYS367
ASP354-LYS367
ASP362-ARG366
ASP354-LYS367
ASP354-LYS367
ASP362-ARG366
ASP362-ARG366
ASP398-ARG382
ASP362-ARG366
ASP362-ARG366
ASP398-ARG382
ASP398-ARG382
ASP459-LYS408
ASP398-ARG382
ASP398-ARG382
ASP459-LYS408
ASP459-ARG604
ASP461-LYS318
ASP459-LYS408
ASP459-ARG604
ASP461-LYS318
ASP459-LYS408
ASP461-LYS406
ASP461-LYS318
ASP459-LYS408
ASP461-LYS406
ASP461-LYS318
ASP482-ARG411
ASP461-LYS406
ASP461-LYS318
ASP482-ARG411
ASP461-LYS406
ASP48-ARG60
ASP461-LYS408
ASP461-LYS406
ASP48-ARG60
ASP461-LYS408
ASP48-LYS61
ASP482-ARG411
ASP482-ARG411
ASP48-LYS61
ASP482-ARG411
ASP493-ARG346
ASP48-ARG60
ASP48-ARG60
ASP493-ARG346
ASP48-ARG60
ASP493-ARG494
ASP48-LYS61
ASP48-LYS61
ASP493-ARG494
ASP48-LYS61
ASP503-ARG437
ASP493-ARG346
ASP493-ARG346
ASP503-ARG437
ASP493-ARG346
ASP503-LYS443
ASP493-ARG494
ASP493-ARG494
ASP503-LYS443
ASP493-ARG494
ASP522-ARG585
ASP503-ARG437
ASP503-ARG437
ASP522-ARG585
ASP503-ARG437
ASP535-LYS575
ASP503-LYS443
ASP503-LYS443
ASP535-LYS575
ASP503-LYS443
ASP569-ARG528
ASP522-ARG585
ASP522-ARG585
ASP569-ARG528
ASP522-ARG585
ASP56-ARG60
ASP535-LYS575
ASP535-LYS575
ASP56-ARG60
ASP535-LYS575
ASP56-LYS61
ASP569-ARG528
ASP569-ARG528
ASP595-ARG437
ASP569-ARG528
ASP595-ARG437
ASP56-ARG60
ASP56-ARG60
ASP601-ARG604
ASP56-ARG60
ASP601-ARG604
ASP595-ARG437
ASP595-ARG437
ASP92-ARG76
ASP595-ARG437
ASP92-ARG76
ASP601-ARG604
ASP601-ARG604
GLU14-LYS318
ASP601-ARG604
GLU14-LYS318
ASP92-ARG76
ASP92-ARG76
GLU178-ARG105
ASP92-ARG76
GLU178-LYS88
GLU178-ARG105
GLU178-ARG105
GLU178-LYS88
GLU178-ARG105
GLU270-LYS269
GLU178-LYS88
GLU178-LYS88
GLU270-ARG222
GLU178-LYS88
GLU288-ARG310
GLU270-ARG222
GLU270-LYS269
GLU270-LYS269
GLU270-ARG222
GLU288-LYS5
GLU270-ARG279
GLU288-LYS137
GLU288-LYS5
GLU270-LYS269
GLU290-ARG131
GLU270-LYS269
GLU288-LYS5
GLU290-ARG131
GLU288-LYS137
GLU290-ARG310
GLU288-LYS5
GLU290-ARG131
GLU290-ARG310
GLU288-LYS5
GLU290-LYS5
GLU290-ARG131
GLU290-ARG310
GLU290-LYS5
GLU290-ARG131
GLU361-ARG346
GLU290-ARG310
GLU290-LYS137
GLU361-ARG346
GLU290-ARG310
GLU361-ARG494
GLU290-LYS5
GLU290-LYS5
GLU484-ARG411
GLU290-LYS137
GLU47-LYS61
GLU320-LYS12
GLU361-ARG346
GLU484-LYS394
GLU290-LYS5
GLU484-ARG411
GLU361-ARG346
GLU47-ARG60
GLU55-ARG188
GLU320-LYS12
GLU484-LYS394
GLU484-ARG411
GLU47-LYS61
GLU55-ARG40
GLU361-ARG346
GLU55-ARG188
GLU484-LYS394
GLU484-ARG411
GLU576-ARG585
GLU361-ARG494
GLU55-ARG40
GLU55-ARG40
GLU484-LYS394
GLU576-LYS575
GLU47-ARG60
GLU55-ARG60
GLU576-LYS575
GLU55-ARG188
GLU594-LYS311
GLU47-LYS61
GLU576-ARG528
GLU594-LYS311
GLU55-ARG40
GLU596-ARG4
GLU484-ARG411
GLU576-ARG585
GLU596-ARG4
GLU576-ARG528
GLU596-LYS311
GLU484-LYS394
GLU576-LYS575
GLU596-ARG437
GLU576-LYS575
GLU55-ARG188
GLU594-LYS311
GLU596-LYS311
GLU594-LYS311
GLU55-ARG40
GLU596-ARG4
GLU596-ARG4
GLU576-ARG528
GLU596-ARG437
GLU596-ARG437
GLU576-LYS575
GLU596-LYS311
GLU596-LYS311
GLU594-ARG4
GLU596-LYS443
GLU596-LYS443
GLU594-LYS311 GLU596-ARG4 GLU596-ARG437 GLU596-LYS311
2.4 Concluding Remarks
89
Table 2.16 SBs of MDs of the dimer-2N3 model of [340] rep1
rep2
rep3
rep4
rep5
ASP153-LYS102
ASP153-ARG298
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP155-LYS100
ASP153-LYS102
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS12
ASP155-LYS100
ASP155-LYS102
ASP155-LYS12
ASP155-LYS102
ASP176-ARG105
ASP155-LYS102
ASP155-LYS12
ASP176-ARG105
ASP155-LYS12
ASP187-ARG188
ASP155-LYS12
ASP176-ARG105
ASP187-ARG188
ASP176-ARG105
ASP187-ARG40
ASP176-ARG105
ASP187-ARG188
ASP187-ARG40
ASP187-ARG188
ASP197-ARG131
ASP187-ARG188
ASP187-ARG40
ASP197-ARG131
ASP187-ARG40
ASP197-LYS137
ASP187-ARG40
ASP197-ARG131
ASP197-LYS137
ASP197-ARG131
ASP216-ARG279
ASP197-ARG131
ASP197-LYS137
ASP216-ARG279
ASP197-LYS137
ASP229-LYS269
ASP197-LYS137
ASP216-ARG279
ASP229-LYS269
ASP216-ARG217
ASP263-ARG222
ASP216-ARG279
ASP229-LYS269
ASP263-ARG222
ASP216-ARG279
ASP289-ARG131
ASP229-LYS269
ASP263-ARG222
ASP289-ARG131
ASP229-LYS269
ASP295-ARG298
ASP263-ARG222
ASP289-ARG131
ASP295-ARG298
ASP263-ARG222
ASP341-LYS397
ASP289-ARG131
ASP295-ARG298
ASP341-LYS397
ASP289-ARG131
ASP34-LYS90
ASP295-ARG298
ASP341-LYS397
ASP34-LYS90
ASP289-LYS137
ASP355-ARG367
ASP341-LYS397
ASP34-LYS90
ASP355-ARG367
ASP295-ARG298
ASP355-LYS368
ASP34-LYS90
ASP355-ARG367
ASP355-LYS368
ASP341-LYS397
ASP363-ARG367
ASP355-ARG367
ASP355-LYS368
ASP363-ARG367
ASP34-LYS90
ASP399-ARG383
ASP355-LYS368
ASP363-ARG367
ASP399-ARG383
ASP355-ARG367
ASP460-LYS409
ASP363-ARG367
ASP399-ARG383
ASP460-ARG605
ASP355-LYS368
ASP462-LYS319
ASP399-ARG383
ASP460-ARG605
ASP460-LYS409
ASP363-ARG367
ASP462-LYS407
ASP460-LYS409
ASP460-LYS409
ASP462-LYS319
ASP399-ARG383
ASP483-ARG412
ASP462-LYS319
ASP462-LYS319
ASP462-LYS407
ASP460-LYS409
ASP48-ARG60
ASP462-LYS407
ASP462-LYS407
ASP462-LYS409
ASP462-LYS319
ASP48-LYS61
ASP483-ARG412
ASP462-LYS409
ASP483-ARG412
ASP462-LYS407
ASP494-ARG347
ASP48-ARG60
ASP483-ARG412
ASP48-ARG60
ASP483-ARG412
ASP494-ARG495
ASP48-LYS61
ASP48-ARG60
ASP48-LYS61
ASP48-ARG60
ASP504-ARG438
ASP494-ARG347
ASP48-LYS61
ASP494-ARG347
ASP48-LYS61
ASP504-LYS444
ASP494-ARG495
ASP494-ARG347
ASP494-ARG495
ASP494-ARG347
ASP523-ARG524
ASP504-ARG438
ASP494-ARG495
ASP504-ARG438
ASP494-ARG495
ASP523-ARG586
ASP504-LYS444
ASP504-ARG438
ASP504-LYS444
ASP504-ARG438
ASP536-LYS576
ASP536-LYS576
ASP504-LYS444
ASP523-ARG586
ASP504-LYS444
ASP56-ARG60
ASP56-ARG60
ASP523-ARG586
ASP536-LYS576
ASP523-ARG586
ASP570-ARG529
ASP570-ARG529
ASP536-LYS576
ASP56-ARG60
ASP536-LYS576
ASP596-ARG438
ASP596-ARG438
ASP56-ARG60
ASP570-ARG529
ASP56-ARG60
ASP602-ARG605
ASP602-ARG605
ASP570-ARG529
ASP596-ARG438
ASP570-ARG529
ASP92-ARG76
ASP92-ARG76
ASP596-ARG438
ASP602-ARG605
ASP596-ARG438
GLU178-ARG105
GLU14-LYS319
ASP602-ARG605
ASP92-ARG76
ASP596-LYS444
GLU178-LYS88
GLU178-ARG105
ASP92-ARG76
GLU14-LYS319
ASP602-ARG605
GLU270-LYS269
GLU178-LYS88
GLU14-LYS319
GLU178-ARG105
ASP92-ARG76
GLU288-LYS5
GLU270-ARG222
GLU178-ARG105
GLU178-LYS88
GLU14-LYS319
GLU290-ARG131
GLU270-LYS269
GLU178-LYS88
GLU270-ARG222
GLU178-ARG105
GLU290-ARG311
GLU288-LYS5
GLU270-ARG222
GLU270-LYS269
GLU178-LYS88
GLU290-LYS5
GLU290-ARG131
GLU270-LYS269
GLU288-LYS5
GLU270-ARG279
GLU354-LYS368
GLU290-ARG311
GLU288-LYS5
GLU290-ARG131
GLU270-LYS269
GLU362-ARG347
GLU290-LYS5
GLU290-ARG131
GLU290-ARG311
GLU288-LYS137
GLU362-ARG495
GLU321-LYS12
GLU290-ARG311
GLU290-LYS5
GLU288-LYS5
GLU485-ARG412
GLU362-ARG347
GLU290-LYS137
GLU321-LYS12
GLU290-ARG131
GLU485-LYS395
GLU47-ARG60
GLU290-LYS5
GLU362-ARG347
GLU290-ARG311
GLU55-ARG188
GLU47-LYS61
GLU321-LYS12
GLU485-ARG412
GLU290-LYS137
GLU55-ARG40
GLU485-ARG412
GLU362-ARG347
GLU485-LYS395
GLU290-LYS5
GLU577-ARG529
GLU485-LYS395
GLU47-ARG60
GLU55-ARG188
GLU321-LYS12
GLU577-LYS576
GLU55-ARG188
GLU485-ARG412
GLU55-ARG40
GLU362-ARG347
GLU595-LYS312
GLU55-ARG40
GLU485-LYS395
GLU577-ARG586
GLU362-ARG495
GLU597-ARG4
GLU577-ARG529
GLU55-ARG188
GLU577-LYS576
GLU485-ARG412
GLU597-ARG438
GLU577-LYS576
GLU55-ARG40
GLU595-ARG4
GLU485-LYS395
GLU597-LYS312
GLU595-ARG4
GLU577-LYS576
GLU595-LYS312
GLU55-ARG188
GLU595-LYS312
GLU595-LYS312
GLU597-ARG4
GLU55-ARG40
GLU597-ARG4
GLU595-LYS444
GLU597-ARG438
GLU577-ARG529
GLU597-ARG438
GLU597-ARG4
GLU597-LYS312
GLU577-LYS576
GLU597-LYS312
GLU597-ARG438
GLU595-LYS312
GLU597-LYS312
GLU595-LYS444 GLU597-ARG4 GLU597-ARG438 GLU597-LYS312 GLU597-LYS444
90
2 3C-Like Protease (3CLpro)
Table 2.17 SBs of MDs of the dimer-2N3-covalent model of [340] rep1
rep2
rep3
rep4
rep5
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-ARG298
ASP153-LYS102
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP153-LYS102
ASP155-LYS100
ASP155-LYS12
ASP155-LYS102
ASP155-LYS12
ASP155-LYS100
ASP155-LYS12
ASP176-ARG105
ASP155-LYS12
ASP176-ARG105
ASP155-LYS12
ASP176-ARG105
ASP187-ARG188
ASP176-ARG105
ASP187-ARG188
ASP176-ARG105
ASP187-ARG188
ASP187-ARG40
ASP187-ARG188
ASP187-ARG40
ASP187-ARG188
ASP187-ARG40
ASP197-ARG131
ASP187-ARG40
ASP197-ARG131
ASP187-ARG40
ASP197-ARG131
ASP197-LYS137
ASP197-ARG131
ASP197-LYS137
ASP197-ARG131
ASP197-LYS137
ASP216-ARG279
ASP197-LYS137
ASP216-ARG279
ASP197-LYS137
ASP216-ARG279
ASP229-LYS269
ASP216-ARG279
ASP229-LYS269
ASP216-ARG279
ASP229-LYS269
ASP263-ARG222
ASP229-LYS269
ASP263-ARG222
ASP229-LYS269
ASP263-ARG222
ASP289-ARG131
ASP263-ARG222
ASP289-ARG131
ASP263-ARG222
ASP289-ARG131
ASP295-ARG298
ASP289-ARG131
ASP289-LYS137
ASP289-ARG131
ASP295-ARG298
ASP340-LYS396
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP340-LYS396
ASP34-LYS90
ASP340-LYS396
ASP340-LYS396
ASP340-LYS396
ASP34-LYS90
ASP354-ARG366
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP354-ARG366
ASP354-LYS367
ASP354-ARG366
ASP354-ARG366
ASP354-ARG366
ASP354-LYS367
ASP362-ARG366
ASP354-LYS367
ASP354-LYS367
ASP354-LYS367
ASP362-ARG366
ASP398-ARG382
ASP362-ARG366
ASP362-ARG366
ASP362-ARG366
ASP398-ARG382
ASP459-ARG604
ASP398-ARG382
ASP398-ARG382
ASP362-LYS367
ASP459-ARG604
ASP459-LYS408
ASP459-ARG604
ASP459-ARG604
ASP398-ARG382
ASP459-LYS408
ASP461-LYS318
ASP459-LYS408
ASP459-LYS408
ASP459-LYS408
ASP461-LYS318
ASP461-LYS406
ASP461-LYS318
ASP461-LYS318
ASP461-LYS318
ASP461-LYS406
ASP461-LYS408
ASP461-LYS406
ASP461-LYS406
ASP461-LYS406
ASP461-LYS408
ASP482-ARG411
ASP482-ARG411
ASP461-LYS408
ASP482-ARG411
ASP482-ARG411
ASP48-ARG60
ASP48-ARG60
ASP482-ARG411
ASP48-ARG60
ASP48-ARG60
ASP48-LYS61
ASP48-LYS61
ASP48-ARG60
ASP48-LYS61
ASP48-LYS61
ASP493-ARG346
ASP493-ARG346
ASP48-LYS61
ASP493-ARG346
ASP493-ARG346
ASP493-ARG494
ASP493-ARG494
ASP493-ARG346
ASP493-ARG494
ASP493-ARG494
ASP503-ARG437
ASP503-ARG437
ASP493-ARG494
ASP503-ARG437
ASP503-ARG437
ASP503-LYS443
ASP503-LYS443
ASP503-ARG437
ASP503-LYS443
ASP503-LYS443
ASP535-LYS575
ASP522-ARG585
ASP503-LYS443
ASP522-ARG585
ASP522-ARG585
ASP569-ARG528
ASP535-LYS575
ASP522-ARG585
ASP535-LYS575
ASP535-LYS575
ASP56-ARG60
ASP569-ARG528
ASP535-LYS575
ASP569-ARG528
ASP569-ARG528
ASP595-ARG437
ASP56-ARG60
ASP569-ARG528
ASP56-ARG60
ASP56-ARG60
ASP601-ARG604
ASP595-ARG437
ASP56-ARG60
ASP595-ARG437
ASP595-ARG437
ASP92-ARG76
ASP601-ARG604
ASP595-ARG437
ASP601-ARG604
ASP595-LYS443
GLU14-LYS318
ASP92-ARG76
ASP601-ARG604
ASP92-ARG76
ASP601-ARG604
GLU178-ARG105
GLU14-LYS318
ASP92-ARG76
GLU14-LYS318
ASP92-ARG76
GLU178-LYS88
GLU178-ARG105
GLU14-LYS318
GLU178-ARG105
GLU178-ARG105
GLU270-ARG222
GLU178-LYS88
GLU178-ARG105
GLU178-LYS88
GLU178-LYS88
GLU270-LYS269
GLU270-LYS269
GLU178-LYS88
GLU270-ARG222
GLU270-LYS269
GLU288-LYS137
GLU288-LYS137
GLU270-LYS269
GLU270-LYS269
GLU288-LYS5
GLU288-LYS5
GLU288-LYS5
GLU288-LYS5
GLU288-LYS5
GLU290-ARG310
GLU290-ARG131
GLU290-ARG131
GLU290-ARG131
GLU290-ARG131
GLU290-LYS5
GLU290-ARG310
GLU290-ARG310
GLU290-ARG310
GLU290-ARG310
GLU353-LYS367
GLU290-LYS5
GLU290-LYS137
GLU290-LYS137
GLU290-LYS5
GLU361-ARG346
GLU320-LYS12
GLU290-LYS5
GLU290-LYS5
GLU353-LYS367
GLU361-ARG494
GLU353-LYS367
GLU361-ARG346
GLU320-LYS12
GLU361-ARG346
GLU484-ARG411
GLU361-ARG346
GLU361-ARG494
GLU361-ARG346
GLU361-ARG366
GLU484-LYS394
GLU361-ARG494
GLU484-ARG411
GLU361-ARG494
GLU47-LYS61
GLU55-ARG188
GLU47-ARG60
GLU484-LYS394
GLU484-ARG411
GLU484-ARG411
GLU55-ARG40
GLU484-ARG411
GLU55-ARG188
GLU484-LYS394
GLU484-LYS394
GLU576-LYS575
GLU484-LYS394
GLU55-ARG40
GLU55-ARG188
GLU55-ARG188
GLU594-LYS311
GLU55-ARG188
GLU576-ARG528
GLU55-ARG40
GLU55-ARG40
GLU596-ARG4
GLU55-ARG40
GLU576-ARG585
GLU576-ARG528
GLU576-ARG528
GLU596-ARG437 GLU596-LYS311
GLU576-ARG585
GLU576-LYS575
GLU576-ARG585
GLU576-ARG585
GLU576-LYS575
GLU594-LYS311
GLU576-LYS575
GLU576-LYS575
GLU594-LYS311
GLU594-LYS443
GLU594-LYS311
GLU594-LYS311
GLU596-ARG4
GLU596-ARG4
GLU596-ARG4
GLU596-ARG4
GLU596-ARG437
GLU596-ARG437
GLU596-LYS311
GLU596-LYS311
GLU596-LYS311 GLU596-LYS443
GLU596-LYS311 GLU596-LYS443
THR201.OG1-GLU240.O 59.0 TRP31.N-CYS16.O 57.5
THR201.OG1-GLU240.O 61.0 SER267.OG-ASP263.O 59.5 VAL36.N-LEU89.O 57.5 SER147.OG-SER144.O 56.0
TYR182.OH-CYS160.O 60.0
SER267.OG-ASP263.O 57.0
TRP31.N-CYS16.O 52.0
TRP31.N-CYS16.O 60.0
TYR182.OH-CYS160.O 58.5
GLY149.N-TYR161.O 47.0
VAL91.N-ASP34.O 38.5
CYS22.N-THR25.O 37.0 ASN151.N-SER158.O 36.5 HIE172.N-ILE136.O 36.5
GLY109.N-MET130.O 39.5 ASN28.ND2-CYS145.O 39.0 ARG131.N-THR135.O 39.0
LEU167.N-VAL171.O 37.0
ASN133.ND2-GLY195.O 36.5
ASN95.ND2-TRP31.O 36.5
GLY146.N-HIE163.O 38.0
ASN203.ND2-ASP289.O 38.0 GLY109.N-MET130.O 38.0
LEU115.N-VAL148.O 39.5 SER254.OG-ILE259.O 39.5
GLY109.N-MET130.O 39.0
ARG131.N-THR135.O 38.0
LEU268.N-MET264.O 38.0
TYR209.OH-ILE259.O 38.0
ARG40.NH2-ASP187.OD2 37.5
ASP176.N-ASN180.O 40.0 ALA70.N-VAL73.O 39.5
VAL157.N-LYS100.O 40.0 GLY146.N-HIE163.O 40.0
VAL18.N-GLY29.O 39.5
SER144.OG-LEU141.O 39.0
LEU208.N-VAL204.O 38.5
ALA234.N-PHE230.O 38.5
THR175.OG1-ASP176.O 37.5
LEU32.N-VAL35.O 38.5
ILE78.N-LYS90.O 40.0 PHE112.N-CYS128.O 40.0
GLU240.N-THR199.O 41.0 ASN95.ND2-TRP31.O 40.5
ASN231.N-LEU227.O 40.5
VAL91.N-ASP34.O 40.0
LEU89.N-VAL36.O 40.0
VAL18.N-GLY29.O 41.0
TYR126.N-VAL114.O 38.5
ILE200.N-ASP289.OD2 38.5
GLN19.N-GLN69.O 39.5
SER254.OG-ILE259.O 39.5
LEU30.N-TYR37.O 40.0
LYS269.N-CYS265.O 40.5
LEU115.N-VAL148.O 40.5
GLY149.N-TYR161.O 40.5
LYS88.N-SER81.O 39.5
LYS88.N-SER81.O 41.0 LEU30.N-TYR37.O 40.5
ILE78.N-LYS90.O 42.0
ASN28.ND2-CYS145.O 41.0
ASN231.N-LEU227.O 42.0
VAL20.N-LEU27.O 41.0
LEU75.N-VAL68.O 41.5
ALA255.N-GLY251.O 41.5
TYR37.N-LEU30.O 41.5
VAL20.N-LEU27.O 42.0
ASN95.N-ASP33.O 42.0
LEU205.N-THR201.O 42.5
ASP176.N-ASN180.O 44.0
GLY146.N-HIE163.O 44.0
LYS88.N-SER81.O 44.0
HIE163.N-SER147.O 44.5
LEU167.N-VAL171.O 46.5
LEU89.N-VAL36.O 46.5
LEU27.N-VAL20.O 47.0
TYR209.OH-ILE259.O 47.0
HIE172.N-ILE136.O 47.5
THR175.OG1-ASP176.O 49.0
TRP31.N-CYS16.O 50.5
VAL114.N-TYR126.O 51.0
ILE78.N-LYS90.O 51.0
SER267.OG-ASP263.O 52.5
THR257.OG1-LEU253.O 52.5
THR201.OG1-GLU240.O 59.5
VAL36.N-LEU89.O 60.0
TYR182.OH-CYS160.O 66.5
rep5
LEU75.N-VAL68.O 41.5
TYR209.OH-ILE259.O 41.0
LEU89.N-VAL36.O 41.5 LEU115.N-VAL148.O 41.5 ASN95.N-ASP33.O 41.0
LEU89.N-VAL36.O 42.5 LEU205.N-THR201.O 41.5 LEU75.N-VAL68.O 41.0
GLU14.N-SER10.O 42.5
LEU75.N-VAL68.O 42.0
VAL20.N-LEU27.O 43.0
GLY146.N-HIE163.O 42.0
LEU27.N-VAL20.O 43.5 VAL157.N-LYS100.O 43.0
LYS88.N-SER81.O 43.0 CYS128.N-PHE112.O 42.5
LEU30.N-TYR37.O 42.5
GLY149.N-TYR161.O 42.5
LEU27.N-VAL20.O 44.5
PHE150.N-SER113.O 43.5
ARG131.N-THR135.O 42.5
THR257.OG1-LEU253.O 44.0 LEU32.N-VAL35.O 43.5
LEU30.N-TYR37.O 44.5 HIE163.N-SER147.O 44.5
LEU27.N-VAL20.O 43.0
CYS128.N-PHE112.O 42.5
LEU30.N-TYR37.O 45.5
SER254.OG-ILE259.O 45.0
ASN203.ND2-ASP289.O 42.0
LEU205.N-THR201.O 45.0 VAL114.N-TYR126.O 44.5
TYR37.N-LEU30.O 45.0 LEU27.N-VAL20.O 45.0
PHE150.N-SER113.O 44.0
LEU115.N-VAL148.O 43.0
LEU205.N-THR201.O 46.5
ILE78.N-LYS90.O 46.0
ASN231.N-LEU227.O 45.5 ASN203.ND2-GLY109.O 45.5
THR135.OG1-ASN133.OD1 46.5
SER254.OG-ILE259.O 44.5
ASN95.N-ASP33.O 44.0
TYR182.N-GLY174.O 46.5 VAL114.N-TYR126.O 45.5
TYR37.N-LEU30.O 45.5 VAL20.N-LEU27.O 45.5
ILE78.N-LYS90.O 48.0 PHE150.N-SER113.O 48.0
ASN95.N-ASP33.O 46.5
TYR209.OH-ILE259.O 45.5
VAL157.N-LYS100.O 45.0
THR257.OG1-LEU253.O 48.0
VAL157.N-LYS100.O 46.5
TYR209.OH-ILE259.O 46.0 SER254.OG-ILE259.O 46.0
ASN95.N-ASP33.O 51.0 THR175.OG1-ASP176.O 50.5 LEU167.N-VAL171.O 49.0
LEU205.N-THR201.O 47.0
VAL114.N-TYR126.O 47.0
SER147.OG-SER144.O 46.0
TYR37.N-LEU30.O 50.0
SER147.OG-SER144.O 48.5
HIE163.N-SER147.O 48.5
HIE163.N-SER147.O 49.5 PHE150.N-SER113.O 47.5
THR257.OG1-LEU253.O 54.5 GLY149.N-TYR161.O 51.5
HIE163.N-SER147.O 49.0
THR257.OG1-LEU253.O 47.0
GLY149.N-TYR161.O 54.5
VAL114.N-TYR126.O 52.5
VAL36.N-LEU89.O 51.0 SER147.OG-SER144.O 50.0
TRP31.N-CYS16.O 55.5
THR135.OG1-ASN133.OD1 51.0
VAL36.N-LEU89.O 50.0
VAL36.N-LEU89.O 58.0
THR135.OG1-ASN133.OD1 57.5
TYR182.OH-CYS160.O 56.0
THR135.OG1-ASN133.OD1 59.5
SER267.OG-ASP263.O 63.0
rep4
THR201.OG1-GLU240.O 65.0
THR201.OG1-GLU240.O 67.5 TYR182.OH-CYS160.O 63.0
rep2
rep1
rep3
Table 2.18 HBs with more than 30% occupancy rates during the five sets (each set runs for 200 ns) of MDs of the monomer-apo model of [340]
(continued)
2.4 Concluding Remarks 91
ALA234.N-PHE230.O 35.0
ALA173.N-MET165.O 37.0
LEU75.N-VAL68.O 36.0
ASN231.N-LEU227.O 34.5
ASN133.ND2-GLY195.O 32.0
CYS265.N-VAL261.O 33.5
SER10.OG-GLU14.OE2 30.0 ILE281.N-SER284.O 30.0 ALA173.N-MET165.O 30.0 LYS90.N-GLY79.O 30.0
LEU67.N-THR21.O 32.0 PHE159.N-LYS102.O 32.0 PHE112.N-CYS128.O 31.5 TYR54.OH-ASP187.OD2 31.0
PHE112.N-CYS128.O 31.0
CYS160.N-GLY149.O 31.0
LEU272.N-LEU268.O 31.0
ALA173.N-MET165.O 31.0
LEU242.N-ASN231.OD1 30.5
TYR239.N-ALA234.O 30.0
ASN133.ND2-GLY195.O 30.0
GLN19.N-GLN69.O 29.5
ASN133.ND2-GLY195.O 30.0
TRP207.N-ASN203.O 29.5
TYR182.N-GLY174.O 29.0
TYR239.N-ALA234.O 29.0
GLY120.N-ASN28.OD1 27.5
ILE200.N-ASP289.OD2 27.5
SER123.N-ALA116.O 27.5
THR21.N-LEU67.O 30.0
ALA210.N-ALA206.O 29.5
LEU57.N-ASN53.O 28.0
ASN151.N-SER158.O 28.0
TYR118.N-SER121.O 30.0
TYR239.N-ALA234.O 30.0
SER113.N-PHE150.O 30.0
LYS102.N-VAL157.O 30.0
LYS269.N-CYS265.O 29.5
TRP207.N-ASN203.O 29.5
TYR209.N-LEU205.O 29.5
ALA211.N-TRP207.O 29.5
CYS128.N-PHE112.O 30.0 ALA255.N-GLY251.O 29.5
ARG131.NH2-ASP289.OD1 31.0 TYR126.N-VAL114.O 30.5
SER10.OG-GLU14.OE1 30.5
ALA255.N-GLY251.O 30.5
THR175.OG1-ASP176.O 30.5
PHE112.N-CYS128.O 29.0
ALA266.N-LEU262.O 29.0
VAL297.N-PRO293.O 30.5
TYR118.N-SER121.O 28.5
ASN203.ND2-GLY109.O 32.5
GLU14.N-SER10.O 31.0 ARG131.N-THR135.O 31.0
GLN83.N-VAL86.O 30.5
SER123.N-ALA116.O 33.0 GLN83.N-VAL86.O 32.5
TYR118.N-SER121.O 32.0
LEU208.N-VAL204.O 31.5
VAL18.N-GLY29.O 31.0
ASP153.N-CYS156.O 31.5
TYR126.N-VAL114.O 31.5
TYR54.OH-ASP187.OD1 32.0
GLN192.NE2-VAL186.O 33.0
LEU268.N-MET264.O 33.0
ASP176.N-ASN180.O 33.5
GLN127.NE2-GLU290.O 31.0
CYS22.N-THR25.O 32.5
SER10.OG-GLU14.OE2 32.0
ALA210.N-ALA206.O 32.0
CYS22.N-THR25.O 32.0
ASP176.N-ASN180.O 33.0
GLN69.N-GLN19.O 32.5
VAL91.N-ASP34.O 32.5
CYS128.N-PHE112.O 32.5
GLY146.N-HIE163.O 32.5 GLN69.N-GLN19.O 32.5 ASN28.ND2-CYS145.O 32.0
VAL91.N-ASP34.O 34.0 CYS22.N-THR25.O 34.0 PHE8.N-SER113.OG 33.5
ALA234.N-PHE230.O 34.0
GLU240.N-THR199.O 33.5
LEU32.N-VAL35.O 33.0
GLN19.N-GLN69.O 33.5
VAL91.N-ASP34.O 33.0
LEU167.N-VAL171.O 33.0
GLN83.N-VAL86.O 33.5
ALA210.N-ALA206.O 34.0
VAL18.N-GLY29.O 33.5
THR21.N-LEU67.O 34.0
VAL18.N-GLY29.O 35.5
LEU32.N-VAL35.O 33.5
ASN151.N-SER158.O 34.5
LEU89.N-VAL36.O 34.0
ALA255.N-GLY251.O 34.5
ASN95.ND2-TRP31.O 34.0
LEU87.N-CYS38.O 35.0 LEU32.N-VAL35.O 34.5
SER113.OG-GLN127.OE1 35.0
ASN203.ND2-ASP289.O 35.0
LYS269.N-CYS265.O 35.5
ASP153.N-CYS156.O 35.0
ASN95.ND2-TRP31.O 34.5
THR175.OG1-ASP176.O 34.0
TRP207.N-ASN203.O 35.0
THR111.OG1-ASP295.OD1 35.5
VAL20.N-LEU27.O 35.5
SER144.OG-LEU141.O 36.0
TYR239.N-ALA234.O 34.5
ALA173.N-MET165.O 35.5
ALA234.N-PHE230.O 36.0
LEU268.N-MET264.O 36.0
SER123.N-ALA116.O 36.0
THR21.N-LEU67.O 36.0
LEU115.N-VAL148.O 36.0
TYR182.N-GLY174.O 36.0 LEU87.N-CYS38.O 35.5
GLU14.N-SER10.O 38.0 TYR182.N-GLY174.O 37.5 ASN203.ND2-ASP289.O 37.5
LYS269.N-CYS265.O 36.0
PHE8.N-SER113.OG 36.0
CYS265.N-VAL261.O 36.0
TYR37.N-LEU30.O 36.0
ALA70.N-VAL73.O 38.5
ILE200.N-ASP289.OD2 36.0
GLN19.N-GLN69.O 38.5
ARG40.NE-ASP187.OD1 36.5
LEU87.N-CYS38.O 36.5
ASN28.ND2-CYS145.O 37.0
rep4
rep3
ALA70.N-VAL73.O 36.5
LYS88.N-SER81.O 36.5
LEU167.N-VAL171.O 37.0
LEU87.N-CYS38.O 36.0
rep2
rep1
Table 2.18 (continued)
MET235.N-ASN231.O 29.5
CYS265.N-VAL261.O 29.5
ASN28.ND2-CYS145.O 29.5
SER113.N-PHE150.O 30.0
GLN83.N-VAL86.O 30.5
THR21.N-LEU67.O 30.5
ASN95.ND2-TRP31.O 30.5
LEU268.N-MET264.O 30.5
ASN203.ND2-ASP289.O 30.5
THR135.OG1-ASN133.OD1 31.0
HID164.ND1-ASP187.O 31.5
TYR209.N-LEU205.O 31.5
TYR154.OH-PRO9.O 32.0
THR292.OG1-ASP295.OD1 32.0
ALA70.N-VAL73.O 32.0
CYS160.N-GLY149.O 32.0
TYR239.N-ALA234.O 32.5
SER147.OG-SER144.O 33.0
LEU272.N-LEU268.O 33.0
PHE112.N-CYS128.O 33.5
ARG131.N-THR135.O 33.5
ALA116.N-GLY124.O 33.5
ALA173.N-MET165.O 34.5
ASN151.N-SER158.O 34.5
TYR182.N-GLY174.O 35.0
GLU14.N-SER10.O 35.0
ALA234.N-PHE230.O 35.5
PHE150.N-SER113.O 35.5
ASN231.N-LEU227.O 36.0
ALA210.N-ALA206.O 36.0
GLY120.N-ASN28.OD1 36.0
VAL157.N-LYS100.O 36.0
THR111.OG1-ASP295.OD2 37.0
LEU87.N-CYS38.O 37.5
rep5
92 2 3C-Like Protease (3CLpro)
rep3
rep4
LEU32.N-VAL35.O 38.0
LEU205.N-THR201.O 37.5
VAL20.N-LEU27.O 37.0
GLN189.N-MET49.O 37.0
GLY109.N-MET130.O 37.0
LEU242.N-ASN231.OD1 38.5
ILE200.N-ASP289.OD1 38.0
SER113.OG-GLN127.OE1 37.5
LEU75.N-VAL68.O 37.5
ALA234.N-PHE230.O 34.0 LYS269.N-CYS265.O 33.5
LEU268.N-MET264.O 34.0
TYR37.N-LEU30.O 37.0 THR175.OG1-ASP176.O 37.0
TYR54.OH-ASP187.OD1 35.0
SER144.OG-LEU141.O 38.5
THR292.OG1-ASP295.OD1 36.5
LEU87.N-CYS38.O 36.0
ASN95.N-ASP33.O 38.5
VAL91.N-ASP34.O 36.5
LEU89.N-VAL36.O 39.0
LYS102.N-VAL157.O 36.5
SER113.OG-GLN127.OE1 38.0
ASN231.N-LEU227.O 39.5
ASN95.ND2-TRP31.O 39.0
ASN203.ND2-ASP289.O 38.5
LEU27.N-VAL20.O 39.5
ALA70.N-VAL73.O 39.0
CYS128.N-PHE112.O 39.0
CYS160.N-GLY149.O 36.5
SER147.OG-SER144.O 37.0
LYS88.N-SER81.O 40.0
GLY146.N-HIE163.O 39.0
LEU32.N-VAL35.O 40.5
TYR54.OH-ASP187.OD2 40.0 VAL18.N-GLY29.O 39.5
LEU89.N-VAL36.O 37.5 VAL157.N-LYS100.O 37.5
VAL20.N-LEU27.O 40.5 ALA234.N-PHE230.O 40.0
LEU89.N-VAL36.O 40.0
LEU75.N-VAL68.O 40.0
LEU115.N-VAL148.O 41.5
GLY146.N-HIE163.O 41.0
ASP176.N-ASN180.O 38.5 GLY149.N-TYR161.O 38.0
ALA173.N-MET165.O 41.0
LEU30.N-TYR37.O 40.5
GLU14.N-SER10.O 40.0
ILE78.N-LYS90.O 42.0
GLN19.N-GLN69.O 42.0
LEU115.N-VAL148.O 40.5
LEU205.N-THR201.O 42.5
ILE136.N-HIE172.O 38.5
SER254.OG-ILE259.O 40.5
THR25.OG1-CYS44.O 43.0
PHE150.N-SER113.O 39.0
THR257.OG1-LEU253.O 42.0
LEU89.N-VAL36.O 41.0
ASN95.ND2-TRP31.O 41.0
LEU87.N-CYS38.O 43.5
LYS88.N-SER81.O 39.0
CYS128.N-PHE112.O 42.0
ILE78.N-LYS90.O 40.5
ASN95.N-ASP33.O 41.5
SER254.OG-ILE259.O 43.5
LEU205.N-THR201.O 39.0
ASN203.ND2-ASP289.O 43.0
PHE112.N-CYS128.O 38.5
LYS88.N-SER81.O 41.5
TYR37.N-LEU30.O 43.5
TYR182.N-GLY174.O 40.5
LEU27.N-VAL20.O 43.0
LEU75.N-VAL68.O 41.5
LEU87.N-CYS38.O 43.0
ASN95.N-ASP33.O 43.5
SER254.OG-ILE259.O 42.0
GLY146.N-HIE163.O 43.5
LEU75.N-VAL68.O 38.5
ASN28.ND2-CYS145.O 44.0
ASN95.N-ASP33.O 42.0
LEU115.N-VAL148.O 43.5
VAL157.N-LYS100.O 46.0
LEU30.N-TYR37.O 43.5
LEU27.N-VAL20.O 44.5
VAL114.N-TYR126.O 47.0
LEU205.N-THR201.O 41.5
THR175.OG1-ASP176.O 44.5
THR175.OG1-ASP176.O 45.5
SER144.OG-LEU141.O 44.5
ASN28.ND2-GLY146.O 42.5
GLU14.N-SER10.O 44.0
HIE163.N-SER147.O 45.0
VAL114.N-TYR126.O 46.5
TYR37.N-LEU30.O 45.0
VAL114.N-TYR126.O 46.0
LEU167.N-VAL171.O 46.0
LEU115.N-VAL148.O 45.0
LEU27.N-VAL20.O 46.5
VAL157.N-LYS100.O 47.0
HIE163.N-SER147.O 45.5
LEU167.N-VAL171.O 46.5
LYS88.N-SER81.O 47.0
CYS128.N-PHE112.O 45.5
ILE78.N-LYS90.O 43.0 VAL20.N-LEU27.O 43.0
ILE78.N-LYS90.O 45.5 ARG131.N-THR135.O 45.0
TYR209.OH-ILE259.O 47.5
TYR209.OH-ILE259.O 47.5
LEU30.N-TYR37.O 45.0
THR135.OG1-ASN133.OD1 47.5
LEU30.N-TYR37.O 48.0 TYR209.OH-ILE259.O 48.0
PHE150.N-SER113.O 48.0 THR175.OG1-ASP176.O 46.0
THR257.OG1-LEU253.O 49.5
GLY149.N-TYR161.O 52.5
SER147.OG-SER144.O 48.5
THR135.OG1-ASN133.OD1 48.5 ASP176.N-ASN180.O 50.0
TRP31.N-CYS16.O 50.5
SER267.OG-ASP263.O 54.0
THR257.OG1-LEU253.O 49.5
GLY149.N-TYR161.O 49.0
THR257.OG1-LEU253.O 48.5 TYR37.N-LEU30.O 46.5
HIE163.N-SER147.O 52.0 VAL114.N-TYR126.O 51.5
TRP31.N-CYS16.O 57.0 VAL36.N-LEU89.O 56.0
GLY149.N-TYR161.O 50.0
VAL157.N-LYS100.O 49.5
VAL36.N-LEU89.O 53.5
VAL20.N-LEU27.O 52.5
SER113.OG-GLN127.OE1 50.5
SER267.OG-ASP263.O 54.0 TYR209.OH-ILE259.O 53.5
TYR182.OH-CYS160.O 58.0 SER147.OG-SER144.O 58.0
VAL36.N-LEU89.O 56.0
SER267.OG-ASP263.O 55.0
SER147.OG-SER144.O 55.0
TRP31.N-CYS16.O 54.5
THR201.OG1-GLU240.O 60.0 VAL36.N-LEU89.O 55.5
HIE163.N-SER147.O 59.0 THR135.OG1-ASN133.OD1 59.0
TRP31.N-CYS16.O 60.0
TYR182.OH-CYS160.O 60.0
TYR182.OH-CYS160.O 62.5
SER267.OG-ASP263.O 60.5
THR201.OG1-GLU240.O 61.5
THR201.OG1-GLU240.O 61.0
rep2
THR201.OG1-GLU240.O 62.5
rep1
TYR182.OH-CYS160.O 63.0
VAL18.N-GLY29.O 39.0
GLN83.N-VAL86.O 39.0
GLY146.N-HIE163.O 39.0
ALA234.N-PHE230.O 39.0
GLU14.N-SER10.O 39.5
ASN95.N-ASP33.O 39.5
LEU205.N-THR201.O 39.5
ASN95.ND2-TRP31.O 40.0
LEU89.N-VAL36.O 40.5
PHE150.N-SER113.O 40.5
HIE163.N-SER147.O 40.5
THR175.N-MET162.O 41.0
SER144.OG-LEU141.O 42.0
SER254.OG-ILE259.O 42.0
LEU75.N-VAL68.O 43.0
VAL157.N-LYS100.O 43.0
LYS88.N-SER81.O 43.5
ILE78.N-LYS90.O 43.5
LEU27.N-VAL20.O 44.0
TYR37.N-LEU30.O 44.0
(continued)
SER113.OG-GLN127.OE1 46.0
CYS128.N-PHE112.O 46.0
LEU167.N-VAL171.O 46.5
VAL114.N-TYR126.O 46.5
LEU30.N-TYR37.O 47.0
LEU115.N-VAL148.O 47.0
GLY149.N-TYR161.O 47.0
TYR209.OH-ILE259.O 48.0
THR175.OG1-ASP176.O 48.5
SER267.OG-ASP263.O 48.5
ASP176.N-ASN180.O 48.5
VAL36.N-LEU89.O 51.5
SER147.OG-SER144.O 52.0
THR257.OG1-LEU253.O 52.5
LEU87.N-CYS38.O 53.0
TYR182.OH-CYS160.O 55.0
THR135.OG1-ASN133.OD1 57.0
TRP31.N-CYS16.O 59.0
THR201.OG1-GLU240.O 65.0
rep5
Table 2.19 HBs with more than three occupancy rates during the five sets (each set runs for 200 ns) of MDs of monomer-N3 model of [340]
2.4 Concluding Remarks 93
SER254.OG-ILE259.O 36.0
LEU167.N-VAL171.O 30.5 LEU67.N-THR21.O 30.5
LEU32.N-VAL35.O 33.0 TYR118.N-SER121.O 33.0
TYR182.N-GLY174.O 35.0
LEU67.N-THR21.O 35.0
THR111.OG1-ASP295.OD2 35.0
LYS269.N-CYS265.O 34.5
TYR182.N-GLY174.O 36.0
ASN95.ND2-TRP31.O 35.0
ASN28.ND2-CYS145.O 34.0
LYS90.N-GLY79.O 27.0
ALA255.N-GLY251.O 31.0
ASP176.N-ASN180.O 32.0
LYS90.N-GLY79.O 31.5
GLU240.N-THR199.O 31.5
GLY109.N-MET130.O 31.5
GLN189.N-MET49.O 30.0 THR111.OG1-ASP295.OD2 29.5
ALA173.N-MET165.O 30.5
LEU208.N-VAL204.O 30.0
ILE136.N-HIE172.O 30.0
TRP207.N-ASN203.O 29.0
GLN299.N-ASP295.O 28.5
LEU242.N-ASN231.OD1 28.0
SER10.OG-GLU14.OE2 30.0
VAL91.N-ASP34.O 30.0
ASN214.N-ALA210.O 30.0
ALA255.N-GLY251.O 29.5
THR21.N-LEU67.O 29.5
ALA210.N-ALA206.O 29.5
LYS102.N-VAL157.O 31.0
LEU67.N-THR21.O 29.5
MET235.N-ASN231.O 30.0
THR25.OG1-CYS44.O 30.0
GLY109.N-MET130.O 30.5
GLU240.N-THR199.O 30.5
TYR126.N-VAL114.O 31.0
THR25.OG1-CYS44.O 31.0
MET235.N-ASN231.O 30.5
LEU272.N-LEU268.O 31.0
LYS269.N-CYS265.O 32.0
LEU268.N-MET264.O 32.0
LEU67.N-THR21.O 30.5
ASN231.N-LEU227.O 31.5
ASN133.ND2-GLY195.O 32.0
ALA70.N-VAL73.O 31.5
LEU268.N-MET264.O 31.5
TYR126.N-VAL114.O 28.0 GLY29.N-VAL18.O 27.5
ASN28.ND2-CYS145.O 31.5 GLN192.NE2-VAL186.O 31.5
ALA70.N-VAL73.O 32.5
PHE8.N-SER113.OG 31.5
CYS22.N-THR25.O 31.0
VAL104.N-PHE159.O 28.0
ASN214.N-ALA210.O 32.0
GLN83.N-VAL86.O 33.0
ARG131.NH2-ASP289.OD1 32.0
CYS265.N-VAL261.O 31.0
THR21.N-LEU67.O 29.5 LEU272.N-LEU268.O 29.5
ASN151.N-SER158.O 25.5
GLN192.NE2-VAL186.O 26.0
CYS128.N-PHE112.O 26.0
ARG131.N-THR135.O 26.0
THR111.OG1-THR292.OG1 26.5
GLN299.N-ASP295.O 26.5
ASN231.N-LEU227.O 26.5
SER123.N-ALA116.O 26.5
THR199.N-ASN238.O 27.0
ASN203.ND2-ASP289.O 28.5
GLU14.N-SER10.O 29.0
LEU32.N-VAL35.O 29.5
PHE8.N-SER113.OG 32.0 GLN19.N-GLN69.O 32.0 LYS90.N-GLY79.O 32.0
TYR118.N-SER121.O 34.0
THR21.N-LEU67.O 34.0
SER113.N-PHE150.O 33.0
GLY146.N-HIE163.O 30.0
TYR239.N-ALA234.O 33.0
TYR182.N-GLY174.O 32.5
ARG40.NH2-ASP187.OD1 32.5
ARG40.NE-ASP187.OD2 33.0
LEU57.N-ASN53.O 29.5
GLN83.N-VAL86.O 32.5
VAL91.N-ASP34.O 34.5
ALA234.N-PHE230.O 34.0
ASN203.ND2-ASP289.O 33.5
ARG40.NH2-ASP187.OD2 30.0
GLY120.N-ASN28.OD1 33.0
THR21.N-LEU67.O 33.0
VAL18.N-GLY29.O 34.5
SER123.N-ALA116.O 34.5
GLU14.N-SER10.O 33.5
THR175.N-MET162.O 31.0
THR45.OG1-ASP48.OD1 31.0
ALA255.N-GLY251.O 31.0
ALA173.N-MET165.O 33.5
PHE112.N-CYS128.O 33.5
ASN231.N-LEU227.O 34.0
VAL91.N-ASP34.O 34.0
GLN189.N-MET49.O 32.0 GLN83.N-VAL86.O 32.0
ASN95.ND2-TRP31.O 32.0
LYS269.N-CYS265.O 36.0
HIE172.N-ILE136.O 34.5
LEU87.N-CYS38.O 35.5
SER144.OG-LEU141.O 35.5
ARG131.NH2-ASP289.OD2 35.5
GLN19.N-GLN69.O 35.0
ARG131.N-THR135.O 36.5 ALA210.N-ALA206.O 35.5
CYS300.N-VAL296.O 33.0 CYS265.N-VAL261.O 32.5
LEU268.N-MET264.O 36.0
PHE150.N-SER113.O 36.0
ASP176.N-ASN180.O 36.0
LEU272.N-LEU268.O 36.0
ASN203.ND2-GLY109.O 36.0
ALA234.N-PHE230.O 37.0
VAL18.N-GLY29.O 36.5
rep4 ARG40.NE-ASP187.OD1 33.5
rep3 LEU167.N-VAL171.O 36.0
rep2
ARG131.N-THR135.O 36.5
rep1
PHE150.N-SER113.O 37.0
Table 2.19 (continued) rep5
LYS90.N-GLY79.O 30.0
GLY120.N-ASN28.OD1 30.0
ALA210.N-ALA206.O 30.5
TYR209.N-LEU205.O 30.5
MET235.N-ASN231.O 32.0
ALA255.N-GLY251.O 32.0
PHE8.N-SER113.OG 32.5
ASN28.ND2-CYS145.O 32.5
ASN221.N-SER267.OG 33.0
GLN19.N-GLN69.O 33.0
THR25.OG1-CYS44.O 33.0
ASN151.N-SER158.O 33.0
CYS22.N-THR25.O 33.5
LEU32.N-VAL35.O 33.5
GLU240.N-THR199.O 34.0
LEU242.N-ASN231.OD1 34.5
ASN203.ND2-ASP289.O 34.5
SER113.N-PHE150.O 35.0
HIE172.N-ILE136.O 35.0
THR111.OG1-ASP295.OD1 35.0
TRP207.N-ASN203.O 35.0
ARG40.N-CYS85.O 35.5
TYR118.N-SER121.O 35.5
TYR126.N-VAL114.O 35.5
LYS269.N-CYS265.O 36.0
VAL20.N-LEU27.O 36.5
ALA70.N-VAL73.O 37.0
ALA173.N-MET165.O 37.5
VAL91.N-ASP34.O 38.5
ARG131.N-THR135.O 38.5
ASN231.N-LEU227.O 38.5
GLY109.N-MET130.O 38.5
94 2 3C-Like Protease (3CLpro)
SER147.OG-SER144.O 48.5
LEU421.N-VAL454.O 45.5 LEU75.N-VAL68.O 45.5
SER560.OG-ILE565.O 47.5 GLY146.N-HIE163.O 47.5
ASP153.N-CYS156.O 46.5
PHE150.N-SER113.O 46.0
LEU338.N-VAL341.O 46.0
THR257.OG1-LEU253.O 45.5
ASN401.ND2-TRP337.O 46.0
SER560.OG-ILE565.O 46.0
LEU115.N-VAL148.O 46.0
PHE456.N-SER419.O 46.0
GLY455.N-TYR467.O 47.0
VAL114.N-TYR126.O 47.0
GLY452.N-HIE469.O 46.5
VAL326.N-LEU333.O 47.5
THR563.OG1-LEU559.O 47.5
VAL157.N-LYS100.O 47.5
LEU473.N-VAL477.O 44.0 LEU167.N-VAL171.O 44.0
TYR37.N-LEU30.O 47.0
TYR515.OH-ILE565.O 44.5 VAL463.N-LYS406.O 44.5
ARG4.NH2-GLU596.OE2 47.0 LEU115.N-VAL148.O 47.0 VAL114.N-TYR126.O 46.5
PHE150.N-SER113.O 45.0
THR481.OG1-ASP482.O 47.0
VAL157.N-LYS100.O 46.5 VAL326.N-LEU333.O 45.5
ILE78.N-LYS90.O 48.0 TYR209.OH-ILE259.O 47.5
VAL420.N-TYR432.O 47.5
LEU30.N-TYR37.O 47.5
THR257.OG1-LEU253.O 48.5
GLY146.N-HIE163.O 46.5
THR481.OG1-ASP482.O 48.0
SER560.OG-ILE565.O 46.5
LEU167.N-VAL171.O 48.5 HIE469.N-SER453.O 48.0
SER147.OG-SER144.O 48.5
TYR343.N-LEU336.O 48.5
THR175.OG1-ASP176.O 49.0
VAL420.N-TYR432.O 47.0 TYR209.OH-ILE259.O 46.5
LEU333.N-VAL326.O 49.0 THR441.OG1-ASN439.OD1 48.5
LEU381.N-VAL374.O 49.0
LYS88.N-SER81.O 49.5
LEU393.N-CYS344.O 48.5
VAL420.N-TYR432.O 49.5
GLY452.N-HIE469.O 47.5 SER254.OG-ILE259.O 47.0
PHE112.N-CYS128.O 49.0 LYS394.N-SER387.O 49.0
GLY149.N-TYR161.O 49.5
TRP31.N-CYS16.O 49.5
THR441.OG1-ASN439.OD1 51.0
LEU421.N-VAL454.O 49.5
TYR343.N-LEU336.O 49.0
LEU395.N-VAL342.O 48.0 ILE78.N-LYS90.O 48.0
GLY149.N-TYR161.O 51.0 VAL420.N-TYR432.O 49.5
LEU473.N-VAL477.O 51.0
TYR209.OH-ILE259.O 50.0
VAL342.N-LEU395.O 51.5
GLN299.NE2-ARG4.O 51.0
TYR37.N-LEU30.O 48.5 HIE469.N-SER453.O 48.5
LEU30.N-TYR37.O 52.0 THR257.OG1-LEU253.O 51.0
ILE78.N-LYS90.O 53.0
THR563.OG1-LEU559.O 52.0
GLY146.N-HIE163.O 51.5
TYR182.OH-CYS160.O 53.0
VAL114.N-TYR126.O 52.5
HIE163.N-SER147.O 52.0
VAL114.N-TYR126.O 50.0 THR257.OG1-LEU253.O 48.5
PHE150.N-SER113.O 52.5 ARG437.N-THR441.O 52.5
GLY455.N-TYR467.O 52.0 THR563.OG1-LEU559.O 51.0
HIE163.N-SER147.O 52.0
PHE456.N-SER419.O 53.5
THR175.OG1-ASP176.O 53.5
SER147.OG-SER144.O 53.5
GLY455.N-TYR467.O 53.0
VAL342.N-LEU395.O 55.5
SER453.OG-SER450.O 53.5
TYR515.OH-ILE565.O 54.0
HIE469.N-SER453.O 53.5
SER453.OG-SER450.O 53.5
SER453.OG-SER450.O 53.0 THR135.OG1-ASN133.OD1 53.0
TRP31.N-CYS16.O 55.0 VAL342.N-LEU395.O 55.0
THR441.OG1-ASN439.OD1 56.5
TRP337.N-CYS322.O 56.5
VAL36.N-LEU89.O 56.0
GLY149.N-TYR161.O 55.0 THR563.OG1-LEU559.O 53.5
TRP31.N-CYS16.O 53.5 VAL36.N-LEU89.O 53.5
ARG131.N-THR135.O 56.0 SER267.OG-ASP263.O 55.5
VAL36.N-LEU89.O 58.5
HIE469.N-SER453.O 57.0
THR507.OG1-GLU546.O 57.5
THR135.OG1-ASN133.OD1 56.5
THR507.OG1-GLU546.O 57.0 TRP337.N-CYS322.O 54.5 SER573.OG-ASP569.O 53.5
TYR182.OH-CYS160.O 60.0 SER573.OG-ASP569.O 60.0 VAL36.N-LEU89.O 56.5
TYR488.OH-CYS466.O 59.0
SER267.OG-ASP263.O 59.0
TYR182.OH-CYS160.O 58.5
TRP337.N-CYS322.O 58.0
SER254.OG-ILE259.O 58.0
TYR182.OH-CYS160.O 60.0 VAL342.N-LEU395.O 57.5
TRP337.N-CYS322.O 61.0 THR201.OG1-GLU240.O 60.5
HIE163.N-SER147.O 61.0
THR135.OG1-ASN133.OD1 60.0
SER445.OG-GLN299.OE1 60.0
TRP31.N-CYS16.O 60.0
SER573.OG-ASP569.O 58.0
SER267.OG-ASP263.O 62.5 THR441.OG1-ASN439.OD1 60.5
THR135.OG1-ASN133.OD1 62.5 THR507.OG1-GLU546.O 62.0
SER573.OG-ASP569.O 63.0
THR201.OG1-GLU240.O 62.0
TYR488.OH-CYS466.O 62.5
TYR488.OH-CYS466.O 63.5 THR201.OG1-GLU240.O 63.5
SER10.OG-GLU14.OE1 77.0 TYR488.OH-CYS466.O 63.5
rep4 SER316.OG-GLU320.OE1 75.0
rep3 SER316.OG-GLU320.OE1 79.5
SER267.OG-ASP263.O 62.0
SER10.OG-GLU14.OE1 78.0
THR507.OG1-GLU546.O 71.0
SER316.OG-GLU320.OE1 79.0
THR201.OG1-GLU240.O 69.5
rep2
SER316.OG-GLU320.OE1 80.0
rep1
SER10.OG-GLU14.OE1 80.5
VAL463.N-LYS406.O 46.0
LEU393.N-CYS344.O 46.0
LEU473.N-VAL477.O 46.5
ILE384.N-LYS396.O 46.5
ASN401.N-ASP339.O 47.5
PHE314.N-SER419.OG 48.0
GLY455.N-TYR467.O 48.0
THR257.OG1-LEU253.O 48.5
PHE150.N-SER113.O 49.0
SER453.OG-SER450.O 49.0
GLY452.N-HIE469.O 49.0
ILE78.N-LYS90.O 49.5
LEU167.N-VAL171.O 49.5
LEU115.N-VAL148.O 49.5
HIE469.N-SER453.O 49.5
TYR515.OH-ILE565.O 50.5
SER254.OG-ILE259.O 51.0
TRP31.N-CYS16.O 51.5
SER267.OG-ASP263.O 52.5
VAL114.N-TYR126.O 53.0
HIE163.N-SER147.O 53.0
PHE112.N-CYS128.O 53.0
VAL342.N-LEU395.O 53.5
VAL420.N-TYR432.O 54.0
(continued)
THR135.OG1-ASN133.OD1 54.0
THR507.OG1-GLU546.O 54.5
SER573.OG-ASP569.O 55.0
VAL36.N-LEU89.O 56.0
SER147.OG-SER144.O 56.5
TYR182.OH-CYS160.O 57.0
TRP337.N-CYS322.O 57.5
THR175.OG1-ASP176.O 57.5
THR563.OG1-LEU559.O 57.5
SER445.OG-GLN299.OE1 59.5
THR441.OG1-ASN439.OD1 60.5
THR201.OG1-GLU240.O 61.0
TYR488.OH-CYS466.O 62.0
SER316.OG-GLU320.OE1 80.0
rep5
Table 2.20 HBs with more than 40% occupancy rates during the five sets (each set runs for 200 ns) of MDs of the dimer-apo model of [340]
2.4 Concluding Remarks 95
THR175.OG1-ASP176.O 45.5
LEU167.N-VAL171.O 44.0
ILE78.N-LYS90.O 44.5
SER445.OG-GLN299.OE1 39.5
LYS5.NZ-GLU290.OE2 39.5
SER450.OG-LEU447.O 39.0
ILE506.N-ASP595.OD2 39.0
LEU27.N-VAL20.O 39.0
ASN203.ND2-GLY109.O 38.5
PHE112.N-CYS128.O 40.0
TYR488.N-GLY480.O 39.5
VAL397.N-ASP340.O 39.5
ASN95.ND2-TRP31.O 40.0
LYS394.N-SER387.O 40.0
ARG437.N-THR441.O 40.0
ASN401.ND2-TRP337.O 40.5
GLY146.N-HIE163.O 40.0
ASN231.N-LEU227.O 39.5
SER254.OG-ILE259.O 40.5
PHE314.N-SER419.OG 40.5
ASP176.N-ASN180.O 39.5
TYR515.OH-ILE565.O 40.5
LEU511.N-THR507.O 41.5
LEU381.N-VAL374.O 41.5
LEU473.N-VAL477.O 42.5
ASN203.ND2-ASP289.O 42.0
ASP459.N-CYS462.O 41.5
LEU115.N-VAL148.O 41.5
LEU336.N-TYR343.O 42.5
LEU336.N-TYR343.O 40.5
PHE314.N-SER419.OG 41.5
ASN95.ND2-TRP31.O 43.0
LEU89.N-VAL36.O 41.5
TYR360.OH-ASP493.OD2 40.0
ASN334.ND2-CYS451.O 42.0
SER429.N-ALA422.O 41.5
TYR209.OH-ILE259.O 43.0
LYS575.N-CYS571.O 41.0
ASN401.N-ASP339.O 42.0
VAL20.N-LEU27.O 43.0
ARG437.N-THR441.O 41.0
VAL463.N-LYS406.O 42.5
ASN95.N-ASP33.O 43.0
PHE112.N-CYS128.O 42.0
ALA479.N-MET471.O 42.5 LEU336.N-TYR343.O 42.5
VAL157.N-LYS100.O 42.5
ASN509.ND2-ASP595.O 41.5
HIE163.N-SER147.O 40.0
ASN95.N-ASP33.O 42.5
SER560.OG-ILE565.O 42.5
ILE384.N-LYS396.O 43.0
HIE172.N-ILE136.O 40.5
LEU393.N-CYS344.O 40.5
LEU87.N-CYS38.O 40.5
VAL20.N-LEU27.O 40.5
ALA210.N-ALA206.O 40.5
ALA540.N-PHE536.O 41.0
ASN401.N-ASP339.O 41.0
PHE8.N-SER113.OG 41.5
LEU421.N-VAL454.O 41.5
LEU32.N-VAL35.O 42.0
ILE136.N-HIE172.O 42.0
PHE418.N-CYS434.O 42.0
ALA70.N-VAL73.O 42.5
CYS434.N-PHE418.O 43.0
VAL157.N-LYS100.O 43.0
ASN509.ND2-ASP595.O 43.0
LEU89.N-VAL36.O 44.0
VAL326.N-LEU333.O 44.5
LEU115.N-VAL148.O 42.5
ASN203.ND2-ASP289.O 37.5
ASN509.ND2-ASP595.O 37.5
CYS328.N-THR331.O 37.5
LYS575.N-CYS571.O 38.0
VAL397.N-ASP340.O 38.5
LEU27.N-VAL20.O 38.5
LEU32.N-VAL35.O 38.5
PHE8.N-SER113.OG 38.5
LYS394.N-SER387.O 39.0
SER10.OG-GLU14.OE2 39.5
ASN401.N-ASP339.O 39.5
PHE314.N-SER419.OG 40.0
GLN299.NE2-ARG4.O 40.0
ARG437.N-THR441.O 40.0
GLY149.N-TYR161.O 40.5
THR481.OG1-ASP482.O 40.5
ALA70.N-VAL73.O 40.5
LEU381.N-VAL374.O 40.5
ASN95.N-ASP33.O 41.5
ILE384.N-LYS396.O 41.5
LEU336.N-TYR343.O 42.0
LEU167.N-VAL171.O 43.5
LEU511.N-THR507.O 45.0 VAL463.N-LYS406.O 45.0
ASN95.N-ASP33.O 43.5
LEU421.N-VAL454.O 42.5
VAL20.N-LEU27.O 43.0
PHE456.N-SER419.O 43.0
VAL91.N-ASP34.O 43.5
LEU30.N-TYR37.O 43.5
LEU333.N-VAL326.O 43.5
LYS88.N-SER81.O 44.0
ASP153.N-CYS156.O 43.5
SER147.OG-SER144.O 45.0
TYR515.OH-ILE565.O 46.0
GLY455.N-TYR467.O 46.0
LEU89.N-VAL36.O 44.0
rep4
LYS88.N-SER81.O 43.5
ILE384.N-LYS396.O 43.5
PHE8.N-SER113.OG 44.5
LEU205.N-THR201.O 44.5
LEU75.N-VAL68.O 43.5
ILE200.N-ASP289.OD2 45.0
ASN401.N-ASP339.O 44.5
GLY452.N-HIE469.O 44.0
PHE456.N-SER419.O 46.0
VAL20.N-LEU27.O 45.0
SER453.OG-SER450.O 45.0
PHE150.N-SER113.O 44.0
TYR343.N-LEU336.O 46.0 GLN605.NE2-ARG310.O 46.0
rep3
rep2
LEU87.N-CYS38.O 45.5
rep1
LEU75.N-VAL68.O 45.5
Table 2.20 (continued)
LEU395.N-VAL342.O 38.0
LEU268.N-MET264.O 38.5
VAL326.N-LEU333.O 38.5
THR327.N-LEU373.O 38.5
ASP176.N-ASN180.O 39.0
SER429.N-ALA422.O 39.0
VAL91.N-ASP34.O 39.0
LEU87.N-CYS38.O 39.5
GLN299.NE2-ARG4.O 40.5
CYS328.N-THR331.O 40.5
TYR182.N-GLY174.O 40.5
ASN95.N-ASP33.O 41.0
CYS128.N-PHE112.O 41.0
LEU30.N-TYR37.O 41.5
LYS394.N-SER387.O 41.5
TYR209.OH-ILE259.O 41.5
PHE456.N-SER419.O 42.0
LEU75.N-VAL68.O 43.0
VAL157.N-LYS100.O 43.0
LYS88.N-SER81.O 43.5
GLY146.N-HIE163.O 43.5
ARG437.N-THR441.O 44.0
GLY149.N-TYR161.O 44.0
ASN537.N-LEU533.O 44.0
SER10.OG-GLU14.OE1 44.5
ASN203.ND2-GLY109.O 44.5
LEU421.N-VAL454.O 44.5
TYR343.N-LEU336.O 44.5
LEU27.N-VAL20.O 45.5
VAL20.N-LEU27.O 45.5
TYR37.N-LEU30.O 45.5
rep5
96 2 3C-Like Protease (3CLpro)
SER267.OG-ASP263.O 65.5 TYR488.OH-CYS466.O 65.0
TYR488.OH-CYS466.O 63.5 TYR182.OH-CYS160.O 62.5
THR507.OG1-GLU546.O 66.5
TYR488.OH-CYS466.O 64.5
TYR488.OH-CYS466.O 69.5
THR507.OG1-GLU546.O 63.0
LEU27.N-VAL20.O 49.5
GLY149.N-TYR161.O 49.5
VAL420.N-TYR432.O 51.0
SER267.OG-ASP263.O 50.5
PHE314.N-SER419.OG 49.5 LEU473.N-VAL477.O 49.0
LEU473.N-VAL477.O 49.0 VAL114.N-TYR126.O 48.5
ARG437.N-THR441.O 46.5
VAL420.N-TYR432.O 46.5
ILE506.N-ASP595.OD2 47.5
ARG310.NH2-GLU290.OE2 47.5
GLY149.N-TYR161.O 47.5
PHE456.N-SER419.O 45.5
TYR209.OH-ILE259.O 45.0
GLY455.N-TYR467.O 45.0
TYR209.OH-ILE259.O 44.5
SER453.OG-SER450.O 44.0
LEU75.N-VAL68.O 44.0
PHE8.N-SER113.OG 46.5 VAL463.N-LYS406.O 46.5 TYR343.N-LEU336.O 46.5
THR481.OG1-ASP482.O 47.0 SER254.OG-ILE259.O 46.5 TYR37.N-LEU30.O 46.0
HIE469.N-SER453.O 47.5 LEU381.N-VAL374.O 47.0
GLY452.N-HIE469.O 47.0 LEU333.N-VAL326.O 47.0 HIE469.N-SER453.O 47.0
LYS88.N-SER81.O 46.0
TYR515.OH-ILE565.O 46.0
SER254.OG-ILE259.O 45.5
ARG310.NH1-GLU290.OE1 46.5
ASN401.N-ASP339.O 45.0
PHE150.N-SER113.O 49.0 TYR209.OH-ILE259.O 48.5
ASN509.ND2-ASP595.O 47.0 ARG131.N-THR135.O 47.0
GLY452.N-HIE469.O 44.5
TYR343.N-LEU336.O 46.5
VAL114.N-TYR126.O 46.0
LYS88.N-SER81.O 47.5
TYR515.OH-ILE565.O 46.5
THR481.OG1-ASP482.O 50.5 GLY452.N-HIE469.O 50.0
THR563.OG1-LEU559.O 50.5 ILE384.N-LYS396.O 49.0
ILE78.N-LYS90.O 47.5
GLY146.N-HIE163.O 47.0
GLY149.N-TYR161.O 48.0
ASN203.ND2-ASP289.O 48.0
TYR515.OH-ILE565.O 51.0 LEU115.N-VAL148.O 51.0
TRP31.N-CYS16.O 51.0 SER453.OG-SER450.O 51.0
HIE478.N-ILE442.O 48.0
LYS394.N-SER387.O 47.5
THR563.OG1-LEU559.O 48.5
PHE456.N-SER419.O 48.5
VAL36.N-LEU89.O 52.5 SER573.OG-ASP569.O 51.5 SER147.OG-SER144.O 51.5
SER573.OG-ASP569.O 52.5 TRP337.N-CYS322.O 51.5 THR441.OG1-ASN439.OD1 51.0
ILE384.N-LYS396.O 48.5
HIE469.N-SER453.O 48.5
LEU421.N-VAL454.O 48.0
THR257.OG1-LEU253.O 50.0
VAL114.N-TYR126.O 54.5 TRP31.N-CYS16.O 54.0
PHE456.N-SER419.O 52.5 SER267.OG-ASP263.O 52.5
THR441.OG1-ASN439.OD1 48.5
LEU167.N-VAL171.O 50.0
THR563.OG1-LEU559.O 54.5 SER139.OG-GLN605.OE1 54.5
PHE150.N-SER113.O 53.0 GLY455.N-TYR467.O 52.5
VAL342.N-LEU395.O 52.0
HIE163.N-SER147.O 49.5
ILE78.N-LYS90.O 52.0
VAL342.N-LEU395.O 51.5
VAL342.N-LEU395.O 54.5 THR441.OG1-ASN439.OD1 54.5
THR257.OG1-LEU253.O 53.5 SER445.OG-GLN299.OE1 53.0
THR135.OG1-ASN133.OD1 54.0
THR441.OG1-ASN439.OD1 53.5
SER450.OG-LEU447.O 53.0
GLY455.N-TYR467.O 52.5
TYR182.OH-CYS160.O 57.5 TRP337.N-CYS322.O 57.0
GLY149.N-TYR161.O 55.0 VAL342.N-LEU395.O 55.0
TRP31.N-CYS16.O 56.0
SER573.OG-ASP569.O 54.5
TRP337.N-CYS322.O 53.5
THR135.OG1-ASN133.OD1 58.0 SER453.OG-SER450.O 57.5
THR507.OG1-GLU546.O 56.5 VAL420.N-TYR432.O 55.5
HIE469.N-SER453.O 53.5
TYR182.OH-CYS160.O 59.0
TRP337.N-CYS322.O 56.0
SER573.OG-ASP569.O 55.0
VAL36.N-LEU89.O 53.5
THR507.OG1-GLU546.O 63.0 THR201.OG1-GLU240.O 62.0 THR257.OG1-LEU253.O 58.0
THR201.OG1-GLU240.O 57.5 VAL36.N-LEU89.O 57.5 THR135.OG1-ASN133.OD1 57.0
THR201.OG1-GLU240.O 64.0
VAL36.N-LEU89.O 60.0
SER267.OG-ASP263.O 59.0
TRP31.N-CYS16.O 59.0
THR201.OG1-GLU240.O 58.5
TYR182.OH-CYS160.O 60.5
SER316.OG-GLU320.OE1 77.5
SER10.OG-GLU14.OE1 72.5
SER10.OG-GLU14.OE1 78.5
SER10.OG-GLU14.OE1 81.0
SER10.OG-GLU14.OE1 78.0
rep4
SER316.OG-GLU320.OE1 78.5
SER316.OG-GLU320.OE1 80.0 SER316.OG-GLU320.OE1 74.5
rep2
rep1
rep3
SER453.OG-SER450.O 45.5
THR481.OG1-ASP482.O 46.0
LEU75.N-VAL68.O 46.0
(continued)
THR135.OG1-ASN133.OD1 46.0
ASP482.N-ASN486.O 46.5
THR257.OG1-LEU253.O 47.0
LEU473.N-VAL477.O 47.5
ILE384.N-LYS396.O 48.0
SER147.OG-SER144.O 49.0
HIE163.N-SER147.O 49.5
LEU115.N-VAL148.O 49.5
THR441.OG1-ASN439.OD1 50.0
GLY149.N-TYR161.O 50.0
TYR209.OH-ILE259.O 50.0
GLY452.N-HIE469.O 50.5
ILE78.N-LYS90.O 50.5
VAL36.N-LEU89.O 51.5
TRP337.N-CYS322.O 51.5
VAL420.N-TYR432.O 52.0
TYR515.OH-ILE565.O 52.5
THR563.OG1-LEU559.O 53.0
HIE469.N-SER453.O 53.0
VAL114.N-TYR126.O 53.5
GLY455.N-TYR467.O 55.0
SER267.OG-ASP263.O 55.5
TYR488.OH-CYS466.O 55.5
VAL342.N-LEU395.O 56.0
THR507.OG1-GLU546.O 59.0
TYR182.OH-CYS160.O 59.5
TRP31.N-CYS16.O 60.0
THR201.OG1-GLU240.O 61.0
SER573.OG-ASP569.O 63.0
SER316.OG-GLU320.OE1 75.5
SER10.OG-GLU14.OE1 81.5
rep5
Table 2.21 HBs with more than 40% occupancy rates during the five sets (each set runs for 200 ns) of MDs of the dimer-N3 model of [340]
2.4 Concluding Remarks 97
ASN95.N-ASP33.O 43.5
ARG310.NH2-GLU290.OE1 44.0 HIE172.N-ILE136.O 43.5
LYS394.N-SER387.O 42.0
LYS88.N-SER81.O 42.5 LEU421.N-VAL454.O 42.5
TYR182.N-GLY174.O 42.5
LEU338.N-VAL341.O 42.5
LEU381.N-VAL374.O 41.5
PHE314.N-SER419.OG 41.0 LEU336.N-TYR343.O 42.5 VAL463.N-LYS406.O 42.5
ASN95.ND2-TRP31.O 41.0 GLN69.N-GLN19.O 40.5 VAL326.N-LEU333.O 40.5 CYS434.N-PHE418.O 40.0 ARG437.N-THR441.O 40.0 THR21.N-LEU67.O 40.0
HIE172.N-ILE136.O 41.0 ASN401.ND2-TRP337.O 40.5 SER560.OG-ILE565.O 40.5 LEU511.N-THR507.O 40.5 PHE8.N-SER113.OG 40.0 GLY146.N-HIE163.O 40.0 VAL157.N-LYS100.O 40.0 LEU30.N-TYR37.O 39.5
LEU511.N-THR507.O 41.5
PHE150.N-SER113.O 41.5
LEU205.N-THR201.O 41.5
VAL18.N-GLY29.O 41.5
PHE8.N-SER113.OG 41.0
VAL157.N-LYS100.O 41.0
LYS311.NZ-GLU596.OE1 40.5
LEU336.N-TYR343.O 40.5
LEU89.N-VAL36.O 39.5
GLY415.N-MET436.O 39.0
LEU205.N-THR201.O 40.5
LEU338.N-VAL341.O 40.5
ARG131.N-THR135.O 40.0
LEU30.N-TYR37.O 40.0
ALA70.N-VAL73.O 40.0
LEU27.N-VAL20.O 40.0
GLY146.N-HIE163.O 40.0
HIE478.N-ILE442.O 39.5
SER123.N-ALA116.O 39.5
ARG40.NH2-ASP187.OD2 39.5
LEU381.N-VAL374.O 41.0
GLN299.NE2-ARG4.O 41.5
LYS269.N-CYS265.O 40.0
SER254.OG-ILE259.O 41.0
TYR488.N-GLY480.O 41.0
LYS5.NZ-GLU290.OE2 41.5
ILE506.N-ASP595.OD1 41.5
HIE163.N-SER147.O 40.5
ASN401.N-ASP339.O 41.5 GLN325.N-GLN375.O 41.5
SER139.OG-GLN605.OE1 42.0
VAL397.N-ASP340.O 41.5
GLN605.NE2-ARG310.O 41.0
ASN95.N-ASP33.O 41.5
PHE456.N-SER419.O 41.5
VAL397.N-ASP340.O 42.0
VAL157.N-LYS100.O 42.0
VAL20.N-LEU27.O 42.5
LEU115.N-VAL148.O 41.0
GLN605.NE2-ARG310.O 42.0
ARG310.NH2-GLU290.OE2 42.5
VAL463.N-LYS406.O 42.0
SER560.OG-ILE565.O 42.0
VAL20.N-LEU27.O 41.0
LEU75.N-VAL68.O 42.5
LEU333.N-VAL326.O 41.0
VAL157.N-LYS100.O 41.0
LEU395.N-VAL342.O 42.5
ILE78.N-LYS90.O 42.5
SER147.OG-SER144.O 42.5
LEU167.N-VAL171.O 42.5
LEU511.N-THR507.O 41.5
TYR37.N-LEU30.O 43.0 LEU393.N-CYS344.O 42.5
VAL326.N-LEU333.O 41.5
HIE163.N-SER147.O 42.5
LEU75.N-VAL68.O 43.0
ASN28.ND2-CYS145.O 43.5
ILE78.N-LYS90.O 43.5
HIE163.N-SER147.O 43.5
SER453.OG-SER450.O 43.0
THR331.OG1-CYS350.O 43.5
ARG40.N-CYS85.O 44.5 ARG310.NH1-GLU290.OE2 44.5
ASN95.ND2-TRP31.O 42.0
VAL20.N-LEU27.O 43.5
ILE384.N-LYS396.O 45.0 VAL420.N-TYR432.O 44.5
TYR37.N-LEU30.O 42.0
LEU30.N-TYR37.O 43.5
THR563.OG1-LEU559.O 43.0
TYR343.N-LEU336.O 42.5
LEU421.N-VAL454.O 42.0
LEU167.N-VAL171.O 45.0 TYR209.OH-ILE259.O 44.5 ARG437.N-THR441.O 44.5
GLY452.N-HIE469.O 44.0
GLN495.N-MET355.O 43.5
ASN95.ND2-TRP31.O 43.5
LYS394.N-SER387.O 42.5
SER147.OG-SER144.O 43.0
LYS394.N-SER387.O 45.0 VAL326.N-LEU333.O 45.0
VAL324.N-GLY335.O 42.5
THR481.OG1-ASP482.O 44.0
ALA234.N-PHE230.O 44.0
LYS5.NZ-GLU290.OE1 43.0
ASN95.N-ASP33.O 43.0
TYR515.OH-ILE565.O 45.0
LEU87.N-CYS38.O 45.5
VAL20.N-LEU27.O 44.5
ASN401.N-ASP339.O 44.0
LEU336.N-TYR343.O 43.5
THR135.OG1-ASN133.OD1 43.5
ILE587.N-SER590.O 45.5
TYR343.N-LEU336.O 45.5 LEU89.N-VAL36.O 45.5
LEU473.N-VAL477.O 44.5
THR257.OG1-LEU253.O 44.5
ILE384.N-LYS396.O 44.0
LEU473.N-VAL477.O 44.0 LEU421.N-VAL454.O 45.5
rep4 ASN401.N-ASP339.O 45.5
rep3 TYR488.N-GLY480.O 46.0
rep2
LEU87.N-CYS38.O 45.0
rep1
SER560.OG-ILE565.O 44.0
Table 2.21 (continued) rep5
ASN509.ND2-ASP595.O 38.5
VAL18.N-GLY29.O 39.0
PHE150.N-SER113.O 39.0
CYS434.N-PHE418.O 39.5
ASN509.ND2-GLY415.O 40.0
SER560.OG-ILE565.O 40.5
ARG131.NH2-ASP289.OD1 41.0
VAL463.N-LYS406.O 41.0
LEU87.N-CYS38.O 41.0
LEU333.N-VAL326.O 41.5
LYS311.NZ-GLU596.OE1 41.5
PHE456.N-SER419.O 41.5
TYR37.N-LEU30.O 41.5
SER139.OG-GLN605.OE1 41.5
VAL397.N-ASP340.O 42.0
LEU27.N-VAL20.O 42.0
GLY146.N-HIE163.O 42.0
ALA70.N-VAL73.O 42.5
ASN95.N-ASP33.O 42.5
LEU511.N-THR507.O 42.5
LEU395.N-VAL342.O 42.5
ASN439.ND2-GLY501.O 43.0
ARG4.NH2-GLU596.OE2 43.5
ASN28.ND2-CYS145.O 43.5
LEU393.N-CYS344.O 43.5
VAL157.N-LYS100.O 44.0
LEU421.N-VAL454.O 44.0
ARG4.NH1-GLU596.OE1 44.5
TYR343.N-LEU336.O 44.5
LYS394.N-SER387.O 44.5
LEU167.N-VAL171.O 45.0
SER254.OG-ILE259.O 45.0
LYS88.N-SER81.O 45.5
98 2 3C-Like Protease (3CLpro)
ARG438.N-THR442.O 46.0
TYR516.OH-ILE566.O 48.0
LEU512.N-THR508.O 47.5
GLY456.N-TYR468.O 47.5
LEU337.N-TYR344.O 47.0
ASN95.ND2-TRP31.O 47.0
LEU75.N-VAL68.O 47.0
LEU337.N-TYR344.O 46.0
VAL327.N-LEU334.O 46.0
LYS88.N-SER81.O 44.5 LYS395.N-SER388.O 44.5
VAL36.N-LEU89.O 46.5 LEU396.N-VAL343.O 46.0
ASN402.N-ASP340.O 45.0 GLY453.N-HIE470.O 45.0
SER254.OG-ILE259.O 46.5 HIE163.N-SER147.O 46.5
GLY146.N-HIE163.O 45.5 ILE385.N-LYS397.O 45.0
HIE172.N-ILE136.O 48.0 THR257.OG1-LEU253.O 47.0 SER147.OG-SER144.O 47.0
GLY146.N-HIE163.O 48.0
HIE172.N-ILE136.O 48.0
THR175.OG1-ASP176.O 48.0
TYR516.OH-ILE566.O 47.5
GLY456.N-TYR468.O 47.0
SER139.OG-GLN606.OE1 47.0
SER446.OG-GLN299.OE1 47.0 THR482.OG1-ASP483.O 46.5
GLY149.N-TYR161.O 48.0 TRP31.N-CYS16.O 48.0
ILE385.N-LYS397.O 48.5
TYR37.N-LEU30.O 48.0
THR175.OG1-ASP176.O 48.0
ARG131.N-THR135.O 47.5
TYR37.N-LEU30.O 48.0 TYR516.OH-ILE566.O 48.0
VAL114.N-TYR126.O 49.0 GLY146.N-HIE163.O 49.0
LYS5.NZ-GLU290.OE1 48.5
LEU422.N-VAL455.O 48.5
LEU167.N-VAL171.O 48.0
VAL421.N-TYR433.O 48.0
SER147.OG-SER144.O 49.0 LEU27.N-VAL20.O 48.5
ILE385.N-LYS397.O 49.5 LEU337.N-TYR344.O 49.5
THR482.OG1-ASP483.O 49.0
VAL421.N-TYR433.O 49.0
LYS5.NZ-GLU290.OE1 48.5
SER454.OG-SER451.O 48.5
PHE457.N-SER420.O 50.0 HIE470.N-SER454.O 49.5
TYR209.OH-ILE259.O 49.5 LYS88.N-SER81.O 49.5
VAL464.N-LYS407.O 50.0
VAL114.N-TYR126.O 49.5
SER446.OG-GLN299.OE1 49.5
TYR209.OH-ILE259.O 51.5 VAL421.N-TYR433.O 50.5 SER454.OG-SER451.O 50.0
THR135.OG1-ASN133.OD1 51.5 THR564.OG1-LEU560.O 50.5 THR175.OG1-ASP176.O 50.0
THR257.OG1-LEU253.O 48.5
SER561.OG-ILE566.O 52.0
TRP338.N-CYS323.O 50.5
GLY149.N-TYR161.O 50.5
HIE172.N-ILE136.O 51.5
ASN402.N-ASP340.O 50.0
THR135.OG1-ASN133.OD1 50.0
TRP31.N-CYS16.O 52.0 THR257.OG1-LEU253.O 51.5
LEU115.N-VAL148.O 52.0 HIE470.N-SER454.O 51.5
THR257.OG1-LEU253.O 53.5
SER139.OG-GLN606.OE1 52.5
VAL114.N-TYR126.O 51.5
LEU115.N-VAL148.O 51.5
VAL343.N-LEU396.O 52.5 GLY149.N-TYR161.O 52.5
TRP338.N-CYS323.O 53.5
THR442.OG1-ASN440.OD1 55.0
TRP31.N-CYS16.O 54.5
VAL343.N-LEU396.O 54.0 LEU167.N-VAL171.O 52.0
THR442.OG1-ASN440.OD1 53.5 THR564.OG1-LEU560.O 53.0
THR482.OG1-ASP483.O 54.5 GLY456.N-TYR468.O 54.0
TRP338.N-CYS323.O 55.5 TYR182.OH-CYS160.O 55.5
THR442.OG1-ASN440.OD1 56.0
HIE470.N-SER454.O 51.5
VAL36.N-LEU89.O 56.0
HIE470.N-SER454.O 55.5
SER267.OG-ASP263.O 56.0
TYR209.OH-ILE259.O 54.0
GLN606.NE2-ARG311.O 57.5
SER574.OG-ASP570.O 57.0
VAL36.N-LEU89.O 57.5
TRP31.N-CYS16.O 57.0
VAL421.N-TYR433.O 55.5
SER574.OG-ASP570.O 57.0 GLY456.N-TYR468.O 56.0
THR508.OG1-GLU547.O 59.0 VAL343.N-LEU396.O 58.5
THR201.OG1-GLU240.O 61.0
LEU167.N-VAL171.O 60.0
GLY149.N-TYR161.O 58.0
THR442.OG1-ASN440.OD1 57.5
THR508.OG1-GLU547.O 60.0 THR201.OG1-GLU240.O 59.0 TYR489.OH-CYS467.O 58.5
SER267.OG-ASP263.O 61.0 SER454.OG-SER451.O 60.0 TYR489.OH-CYS467.O 59.0
TYR489.OH-CYS467.O 61.5
THR135.OG1-ASN133.OD1 61.5
THR508.OG1-GLU547.O 61.5
TRP338.N-CYS323.O 59.5
TYR182.OH-CYS160.O 59.0
THR508.OG1-GLU547.O 61.0
SER267.OG-ASP263.O 61.5 THR135.OG1-ASN133.OD1 60.5
SER574.OG-ASP570.O 64.5
VAL343.N-LEU396.O 62.0
TYR182.OH-CYS160.O 62.0
THR201.OG1-GLU240.O 63.0
SER574.OG-ASP570.O 62.0
TYR182.OH-CYS160.O 63.0
SER10.OG-GLU14.OE1 73.5 VAL36.N-LEU89.O 61.5
SER317.OG-GLU321.OE1 79.5 THR201.OG1-GLU240.O 65.5
SER10.OG-GLU14.OE1 79.5
SER267.OG-ASP263.O 62.5
SER10.OG-GLU14.OE1 77.5
TYR489.OH-CYS467.O 63.5
rep4 SER317.OG-GLU321.OE1 76.5
rep3 SER10.OG-GLU14.OE1 80.5
rep2
SER317.OG-GLU321.OE1 80.0
rep1
SER317.OG-GLU321.OE1 81.0
LEU167.N-VAL171.O 47.5
(continued)
SER139.OG-GLN606.OE1 47.5
ILE385.N-LYS397.O 47.5
GLN606.NE2-ARG311.O 48.0
THR257.OG1-LEU253.O 48.0
HIE470.N-SER454.O 48.0
LEU30.N-TYR37.O 48.5
GLY149.N-TYR161.O 48.5
PHE112.N-CYS128.O 48.5
TYR516.OH-ILE566.O 48.5
TYR209.OH-ILE259.O 48.5
PHE457.N-SER420.O 49.0
ILE78.N-LYS90.O 49.5
HIE163.N-SER147.O 49.5
GLY453.N-HIE470.O 49.5
PHE150.N-SER113.O 50.5
ARG438.N-THR442.O 50.5
HIE172.N-ILE136.O 50.5
VAL114.N-TYR126.O 51.0
VAL343.N-LEU396.O 53.0
SER267.OG-ASP263.O 53.5
GLY456.N-TYR468.O 53.5
THR482.OG1-ASP483.O 53.5
VAL36.N-LEU89.O 53.5
THR442.OG1-ASN440.OD1 53.5
SER574.OG-ASP570.O 55.0
SER10.OG-GLU14.OE1 57.5
THR135.OG1-ASN133.OD1 58.5
TRP31.N-CYS16.O 59.0
TRP338.N-CYS323.O 59.5
TYR489.OH-CYS467.O 59.5
SER446.OG-GLN299.OE1 62.0
TYR182.OH-CYS160.O 63.0
THR201.OG1-GLU240.O 63.5
THR508.OG1-GLU547.O 66.5
SER317.OG-GLU321.OE1 82.0
rep5
Table 2.22 HBs with more than 40% occupancy rates during the five sets (each set runs for 200 ns) of MDs of the dimer-2N3 model of [340]
2.4 Concluding Remarks 99
LEU30.N-TYR37.O 43.5
VAL325.N-GLY336.O 45.0 ILE200.N-ASP289.OD2 44.0
TYR489.N-GLY481.O 42.5 LEU89.N-VAL36.O 42.5
LEU87.N-CYS38.O 43.0 PHE457.N-SER420.O 43.0
LEU115.N-VAL148.O 45.0
ASN95.N-ASP33.O 45.0
ASN28.ND2-CYS145.O 43.5
LEU205.N-THR201.O 42.0
HIE479.N-ILE443.O 42.5
LEU339.N-VAL342.O 41.0
GLU240.N-THR199.O 41.5
LEU30.N-TYR37.O 40.5 SER446.OG-GLN299.OE1 40.5
LEU30.N-TYR37.O 42.5
ASP483.N-ASN487.O 42.5
SER147.OG-SER144.O 41.5
LEU512.N-THR508.O 41.0
ALA480.N-MET472.O 41.0
ASN510.ND2-ASP596.O 40.5
LEU89.N-VAL36.O 40.5
LEU394.N-CYS345.O 40.0
LEU382.N-VAL375.O 39.5
LYS395.N-SER388.O 39.0
PHE315.N-SER420.OG 39.0
ASP176.N-ASN180.O 39.0
LEU382.N-VAL375.O 41.0
LYS88.N-SER81.O 41.0
ASN133.ND2-GLY195.O 40.0
GLN83.N-VAL86.O 40.0
TYR54.OH-ASP187.OD2 40.0 ARG131.N-THR135.O 39.5
GLY416.N-MET437.O 39.0
ASP483.N-ASN487.O 38.5
LYS576.N-CYS572.O 38.5
ASN510.ND2-GLY416.O 38.5
LEU422.N-VAL455.O 39.0
ARG311.NH1-GLU290.OE1 39.0
ARG4.NH2-GLU597.OE2 38.0
ASP483.N-ASN487.O 38.0
ALA480.N-MET472.O 38.0
ASN203.ND2-ASP289.O 38.5
LEU115.N-VAL148.O 38.5
VAL327.N-LEU334.O 39.0
PHE8.N-SER113.OG 39.0
LEU474.N-VAL478.O 39.5 LEU382.N-VAL375.O 39.0 ARG438.NH2-ASP596.OD2 39.0
ALA234.N-PHE230.O 41.5
LYS395.N-SER388.O 41.5
GLN496.N-MET356.O 41.5
ALA541.N-PHE537.O 40.0
ARG4.NH2-GLU597.OE1 40.5
ASP460.N-CYS463.O 40.0
THR418.OG1-ASP602.OD2 40.0
THR482.OG1-ASP483.O 40.5
VAL114.N-TYR126.O 40.0
VAL327.N-LEU334.O 39.5
LEU75.N-VAL68.O 42.0
ASN538.N-LEU534.O 41.5
GLN606.NE2-ARG311.O 41.0
PHE150.N-SER113.O 40.5 GLN326.N-GLN376.O 40.0
PHE150.N-SER113.O 40.5
ARG438.N-THR442.O 40.0
ARG438.N-THR442.O 42.0
ASN203.ND2-GLY109.O 42.0
GLY146.N-HIE163.O 41.0
ASN95.ND2-TRP31.O 40.5
PHE315.N-SER420.OG 40.5
ASN538.N-LEU534.O 40.5
LEU422.N-VAL455.O 41.0
ASN203.ND2-ASP289.O 40.5
ASN402.N-ASP340.O 40.5
VAL157.N-LYS100.O 43.0
TYR489.N-GLY481.O 42.5
LEU339.N-VAL342.O 42.0
ASN402.ND2-TRP338.O 41.5
ARG4.NH1-GLU597.OE1 41.5 GLY416.N-MET437.O 41.0 LEU75.N-VAL68.O 41.0
GLN83.N-VAL86.O 42.0 GLY453.N-HIE470.O 41.5 ASN231.N-LEU227.O 41.5
ARG311.NH2-GLU290.OE1 43.5
ASN203.ND2-ASP289.O 43.0
LEU474.N-VAL478.O 43.0
THR564.OG1-LEU560.O 42.0
ILE78.N-LYS90.O 42.0
HIE163.N-SER147.O 42.5
LEU334.N-VAL327.O 42.0
SER144.OG-LEU141.O 42.0
THR332.OG1-CYS351.O 43.0
TYR37.N-LEU30.O 42.0
ASN402.N-ASP340.O 44.0
PHE457.N-SER420.O 43.5
CYS22.N-THR25.O 42.5
ILE385.N-LYS397.O 42.0
ASP176.N-ASN180.O 42.5
PHE150.N-SER113.O 42.5
SER144.OG-LEU141.O 44.0
LEU334.N-VAL327.O 44.0
LEU87.N-CYS38.O 42.5
ASN510.ND2-ASP596.O 42.5
ILE78.N-LYS90.O 42.5
VAL157.N-LYS100.O 43.0
ASP176.N-ASN180.O 45.0
THR564.OG1-LEU560.O 44.5
PHE8.N-SER113.OG 43.0
LEU334.N-VAL327.O 42.5
VAL464.N-LYS407.O 42.5
ILE78.N-LYS90.O 43.5
ASN95.N-ASP33.O 43.0 VAL20.N-LEU27.O 43.0
SER254.OG-ILE259.O 43.0
ASN95.ND2-TRP31.O 44.0 LEU334.N-VAL327.O 43.5
ASP460.N-CYS463.O 45.5
PHE150.N-SER113.O 45.0
ARG438.N-THR442.O 43.5
LEU382.N-VAL375.O 43.0
LEU167.N-VAL171.O 43.0
VAL157.N-LYS100.O 44.0
SER561.OG-ILE566.O 43.5
PHE8.N-SER113.OG 44.0
TYR344.N-LEU337.O 46.0
LEU396.N-VAL343.O 45.5
LEU87.N-CYS38.O 45.5
LEU30.N-TYR37.O 44.0
TYR516.OH-ILE566.O 45.5
GLY453.N-HIE470.O 43.5
LYS88.N-SER81.O 44.5
VAL464.N-LYS407.O 44.0
TYR344.N-LEU337.O 45.0
ILE78.N-LYS90.O 46.5
SER454.OG-SER451.O 46.5
TYR344.N-LEU337.O 44.5
LEU396.N-VAL343.O 44.0
VAL20.N-LEU27.O 44.5
TYR344.N-LEU337.O 44.5
LYS395.N-SER388.O 45.5 VAL464.N-LYS407.O 45.5
TYR209.OH-ILE259.O 47.0
ARG131.N-THR135.O 46.5
PHE457.N-SER420.O 45.0
LEU396.N-VAL343.O 44.5
rep4 LEU422.N-VAL455.O 44.5
rep3 LEU75.N-VAL68.O 45.5
rep2
HIE163.N-SER147.O 47.0
rep1
ARG311.NH1-GLU290.OE1 46.0
Table 2.22 (continued) rep5
LEU75.N-VAL68.O 39.0
LEU115.N-VAL148.O 40.0
SER254.OG-ILE259.O 40.5
LYS395.N-SER388.O 40.5
ASP460.N-CYS463.O 41.0
SER147.OG-SER144.O 41.0
HIE41.NE2-ASP187.OD1 41.5
VAL91.N-ASP34.O 41.5
LEU89.N-VAL36.O 41.5
LEU422.N-VAL455.O 41.5
THR25.OG1-CYS44.O 42.0
PHE419.N-CYS435.O 42.0
ASN203.ND2-GLY109.O 42.0
ASP483.N-ASN487.O 42.5
LEU337.N-TYR344.O 42.5
LEU27.N-VAL20.O 43.0
LEU474.N-VAL478.O 43.0
GLY146.N-HIE163.O 43.0
TYR37.N-LEU30.O 43.0
LYS88.N-SER81.O 43.0
VAL464.N-LYS407.O 43.0
ASN402.N-ASP340.O 43.5
PHE8.N-SER113.OG 43.5
ASN95.N-ASP33.O 43.5
PHE315.N-SER420.OG 43.5
TYR344.N-LEU337.O 44.5
GLN299.NE2-ARG4.O 45.5
LEU87.N-CYS38.O 45.5
ASN95.ND2-TRP31.O 45.5
ILE507.N-ASP596.OD2 45.5
ASN538.N-LEU534.O 45.5
VAL157.N-LYS100.O 46.0
TYR489.N-GLY481.O 46.0
SER561.OG-ILE566.O 47.0
LEU334.N-VAL327.O 47.0
THR564.OG1-LEU560.O 47.0
VAL421.N-TYR433.O 47.0
SER454.OG-SER451.O 47.0
100 2 3C-Like Protease (3CLpro)
SER10.OG-GLU14.OE1 79.0
SER316.OG-GLU320.OE1 74.0
THR507.OG1-GLU546.O 66.0
THR563.OG1-LEU559.O 51.5
SER147.OG-SER144.O 52.0
GLY149.N-TYR161.O 48.5 GLY455.N-TYR467.O 48.0 LEU421.N-VAL454.O 47.5
LEU30.N-TYR37.O 49.0 PHE150.N-SER113.O 49.0 THR257.OG1-LEU253.O 48.5
HIE163.N-SER147.O 47.5
ILE78.N-LYS90.O 47.5
HIE469.N-SER453.O 47.0
VAL114.N-TYR126.O 47.0
VAL36.N-LEU89.O 48.5
ASN95.N-ASP33.O 47.5
LEU27.N-VAL20.O 47.5
LEU336.N-TYR343.O 47.5
SER445.OG-GLN299.OE1 47.0 TYR515.OH-ILE565.O 47.0 SER453.OG-SER450.O 46.5 TYR37.N-LEU30.O 46.0 TYR343.N-LEU336.O 46.0
CYS328.N-THR331.O 47.5 LEU115.N-VAL148.O 47.5 ARG310.NH1-GLU290.OE1 47.0 GLY149.N-TYR161.O 47.0 LEU167.N-VAL171.O 46.0
LEU115.N-VAL148.O 47.0
THR563.OG1-LEU559.O 47.0
LEU167.N-VAL171.O 47.0
TYR37.N-LEU30.O 46.5
THR257.OG1-LEU253.O 46.0
SER254.OG-ILE259.O 45.5
TYR360.OH-ASP493.O 45.0
GLY455.N-TYR467.O 47.5
VAL463.N-LYS406.O 46.0
TYR209.OH-ILE259.O 45.5
PHE456.N-SER419.O 47.5
ASN401.N-ASP339.O 48.0
VAL114.N-TYR126.O 49.0 HIE163.N-SER147.O 49.0
VAL114.N-TYR126.O 49.5 ARG131.N-THR135.O 49.0
LEU336.N-TYR343.O 48.0
SER450.OG-LEU447.O 48.0
VAL114.N-TYR126.O 49.0
ASN95.N-ASP33.O 49.5 HIE469.N-SER453.O 49.0
ASN95.N-ASP33.O 50.0 TYR37.N-LEU30.O 49.5
VAL157.N-LYS100.O 50.5 LEU473.N-VAL477.O 50.0
HIE469.N-SER453.O 50.5 THR135.OG1-ASN133.OD1 50.0
LEU87.N-CYS38.O 51.0 LYS88.N-SER81.O 50.5
LEU473.N-VAL477.O 51.5 THR563.OG1-LEU559.O 51.0
LEU333.N-VAL326.O 48.5
LEU473.N-VAL477.O 49.5
GLY455.N-TYR467.O 49.0
SER453.OG-SER450.O 50.0
VAL420.N-TYR432.O 49.0
TYR209.OH-ILE259.O 50.0
PHE456.N-SER419.O 50.0
THR441.OG1-ASN439.OD1 50.0
HIE469.N-SER453.O 50.0
SER573.OG-ASP569.O 52.0
VAL420.N-TYR432.O 51.5
TRP31.N-CYS16.O 51.0
LEU167.N-VAL171.O 54.0
THR257.OG1-LEU253.O 52.5
HIE163.N-SER147.O 51.0
THR135.OG1-ASN133.OD1 52.5 VAL420.N-TYR432.O 52.0
THR441.OG1-ASN439.OD1 52.0 LYS311.NZ-GLU596.OE1 52.0
THR481.OG1-ASP482.O 52.5
GLY452.N-HIE469.O 52.5
HIE172.N-ILE136.O 54.5
SER573.OG-ASP569.O 54.0
THR257.OG1-LEU253.O 54.0 SER254.OG-ILE259.O 53.0
SER453.OG-SER450.O 52.5 GLY455.N-TYR467.O 52.5
THR135.OG1-ASN133.OD1 54.5
SER453.OG-SER450.O 53.0
SER147.OG-SER144.O 55.0
TRP337.N-CYS322.O 54.5
TRP31.N-CYS16.O 57.0 SER267.OG-ASP263.O 55.0
SER573.OG-ASP569.O 53.5
GLY149.N-TYR161.O 56.5
TRP337.N-CYS322.O 55.0
THR563.OG1-LEU559.O 55.5
TRP337.N-CYS322.O 54.5
THR441.OG1-ASN439.OD1 58.0 VAL342.N-LEU395.O 57.0
SER445.OG-GLN299.OE1 55.5 VAL342.N-LEU395.O 55.0
THR201.OG1-GLU240.O 58.5 TRP337.N-CYS322.O 58.0
TYR488.OH-CYS466.O 60.0 TRP31.N-CYS16.O 55.5
THR481.OG1-ASP482.O 55.0
VAL36.N-LEU89.O 58.5
SER267.OG-ASP263.O 58.5
THR135.OG1-ASN133.OD1 57.5
LEU87.N-CYS38.O 56.0
VAL342.N-LEU395.O 59.5
SER445.OG-GLN299.OE1 58.5
SER267.OG-ASP263.O 59.5
SER316.OG-GLU320.OE1 59.5
THR507.OG1-GLU546.O 62.0 SER573.OG-ASP569.O 58.5 VAL36.N-LEU89.O 58.5
TYR182.OH-CYS160.O 62.5 VAL36.N-LEU89.O 61.0 SER267.OG-ASP263.O 60.0
TYR488.OH-CYS466.O 61.0
THR175.OG1-ASP176.O 60.0
THR441.OG1-ASN439.OD1 59.5
THR201.OG1-GLU240.O 60.5
THR507.OG1-GLU546.O 60.5
VAL342.N-LEU395.O 59.5
TYR488.OH-CYS466.O 65.0 TYR182.OH-CYS160.O 62.5
THR507.OG1-GLU546.O 66.0 THR201.OG1-GLU240.O 66.0
TYR182.OH-CYS160.O 64.0
THR201.OG1-GLU240.O 61.5
TYR182.OH-CYS160.O 62.0
TYR488.OH-CYS466.O 61.0
SER316.OG-GLU320.OE1 79.0
TRP31.N-CYS16.O 64.0
rep4
SER316.OG-GLU320.OE1 78.5
SER10.OG-GLU14.OE1 81.0 SER10.OG-GLU14.OE1 80.0
rep2
rep1
rep3
ILE200.N-ASP289.OD2 47.0
SER450.OG-LEU447.O 47.5
THR257.OG1-LEU253.O 48.0
ARG131.N-THR135.O 48.5
VAL420.N-TYR432.O 48.5
PHE456.N-SER419.O 49.5
(continued)
HIE347.NE2-ASP493.OD2 50.0
LEU473.N-VAL477.O 50.0
VAL114.N-TYR126.O 50.0
LEU167.N-VAL171.O 51.0
GLY455.N-TYR467.O 51.0
TRP337.N-CYS322.O 51.5
TRP31.N-CYS16.O 52.5
VAL36.N-LEU89.O 52.5
PHE150.N-SER113.O 53.0
VAL342.N-LEU395.O 53.0
THR135.OG1-ASN133.OD1 53.5
SER10.OG-GLU14.OE1 53.5
TYR360.OH-ASP493.O 53.5
SER445.OG-GLN299.OE1 54.0
HIE469.N-SER453.O 54.0
ILE78.N-LYS90.O 55.0
SER573.OG-ASP569.O 55.5
THR563.OG1-LEU559.O 55.5
SER453.OG-SER450.O 56.5
LEU87.N-CYS38.O 57.5
THR201.OG1-GLU240.O 58.0
SER267.OG-ASP263.O 58.0
SER147.OG-SER144.O 59.5
THR441.OG1-ASN439.OD1 59.5
HIE163.N-SER147.O 59.5
THR507.OG1-GLU546.O 60.5
TYR488.OH-CYS466.O 66.0
TYR182.OH-CYS160.O 73.0
SER316.OG-GLU320.OE1 79.5
rep5
Table 2.23 HBs with more than 40% occupancy rates during the five sets (each set runs for 200 ns) of MDs of the dimer-2N3-covalent model of [340]
2.4 Concluding Remarks 101
rep2
HIE478.N-ILE442.O 45.5
HIE172.N-ILE136.O 45.5
LEU30.N-TYR37.O 45.5
VAL326.N-LEU333.O 45.5
CYS328.N-THR331.O 45.5
ILE200.N-ASP289.OD2 45.0
LYS88.N-SER81.O 45.0
LEU393.N-CYS344.O 45.0
ASN95.N-ASP33.O 44.5
LYS394.N-SER387.O 44.5
ARG131.N-THR135.O 44.5
LEU421.N-VAL454.O 44.0
ASN95.ND2-TRP31.O 44.0
SER10.OG-GLU14.OE2 44.0
ASP482.N-ASN486.O 43.5
PHE314.N-SER419.OG 43.5
SER254.OG-ILE259.O 43.0
TYR515.OH-ILE565.O 43.0
LEU89.N-VAL36.O 43.0
ILE384.N-LYS396.O 42.5
SER147.OG-SER144.O 42.5
ASN509.ND2-ASP595.O 42.0
GLN83.N-VAL86.O 42.0
TYR343.N-LEU336.O 42.0
ASN401.ND2-TRP337.O 41.5
ASN203.ND2-ASP289.O 41.5
VAL91.N-ASP34.O 41.0
LEU511.N-THR507.O 40.5
VAL463.N-LYS406.O 40.5
VAL157.N-LYS100.O 40.5
LEU75.N-VAL68.O 40.5
THR331.OG1-CYS350.O 40.5
ARG437.N-THR441.O 39.5
LEU338.N-VAL341.O 39.5
SER560.OG-ILE565.O 39.5
rep1
LEU421.N-VAL454.O 45.0
SER560.OG-ILE565.O 45.0
HIE478.N-ILE442.O 44.5
LEU75.N-VAL68.O 44.0
LYS88.N-SER81.O 44.0
VAL324.N-GLY335.O 43.5
PHE456.N-SER419.O 43.5
LEU89.N-VAL36.O 43.5
LEU205.N-THR201.O 43.5
ILE384.N-LYS396.O 43.0
VAL157.N-LYS100.O 43.0
ILE78.N-LYS90.O 43.0
ASN509.ND2-ASP595.O 43.0
LEU115.N-VAL148.O 43.0
ASN401.ND2-TRP337.O 42.5
GLN83.N-VAL86.O 42.5
ARG437.NH2-ASP595.OD2 42.5
TYR515.OH-ILE565.O 42.5
LEU473.N-VAL477.O 42.0
SER445.OG-GLN299.OE1 42.0
PHE314.N-SER419.OG 41.5
PHE150.N-SER113.O 41.5
ILE506.N-ASP595.OD2 41.5
ARG131.N-THR135.O 41.5
LYS394.N-SER387.O 41.5
ASP482.N-ASN486.O 41.5
TYR343.N-LEU336.O 41.0
LEU511.N-THR507.O 41.0
TYR37.N-LEU30.O 41.0
LEU32.N-VAL35.O 40.5
VAL20.N-LEU27.O 40.5
THR331.OG1-CYS350.O 40.0
TYR424.N-SER427.O 40.0
GLY149.N-TYR161.O 40.0
ASN537.N-LEU533.O 40.0
Table 2.23 (continued) rep3
LEU333.N-VAL326.O 39.5
MET471.N-ALA479.O 40.0
LEU574.N-MET570.O 40.5
CYS22.N-THR25.O 40.5
LEU32.N-VAL35.O 40.5
PHE314.N-SER419.OG 40.5
LEU336.N-TYR343.O 40.5
ILE78.N-LYS90.O 40.5
LYS394.N-SER387.O 40.5
ASN203.ND2-ASP289.O 41.0
ARG437.N-THR441.O 41.0
PHE8.N-SER113.OG 41.0
SER254.OG-ILE259.O 41.0
LEU75.N-VAL68.O 41.5
LEU381.N-VAL374.O 41.5
LEU393.N-CYS344.O 42.0
ASN509.ND2-GLY415.O 42.5
THR175.OG1-ASP176.O 42.5
GLY415.N-MET436.O 42.5
SER560.OG-ILE565.O 43.0
VAL420.N-TYR432.O 43.0
LYS88.N-SER81.O 43.0
ASN401.ND2-TRP337.O 43.0
TYR209.OH-ILE259.O 43.5
GLY452.N-HIE469.O 43.5
TYR343.N-LEU336.O 43.5
LEU395.N-VAL342.O 44.0
THR25.OG1-CYS44.O 44.5
LEU89.N-VAL36.O 44.5
LEU87.N-CYS38.O 44.5
HIE163.N-SER147.O 44.5
PHE456.N-SER419.O 44.5
LEU421.N-VAL454.O 44.5
TYR515.OH-ILE565.O 45.5
LYS5.NZ-GLU290.OE1 46.0
rep4
ALA255.N-GLY251.O 39.0
ASN509.ND2-ASP595.O 39.5
SER123.N-ALA116.O 39.5
LEU511.N-THR507.O 40.0
ASN133.ND2-GLY195.O 40.0
GLN83.N-VAL86.O 40.5
PHE150.N-SER113.O 40.5
ARG310.NH2-GLU290.OE2 40.5
LYS5.NZ-GLU290.OE1 40.5
HIE172.N-ILE136.O 41.0
LYS394.N-SER387.O 41.0
VAL324.N-GLY335.O 41.5
ASN95.ND2-TRP31.O 41.5
ASN401.ND2-TRP337.O 41.5
ARG131.N-THR135.O 42.0
VAL463.N-LYS406.O 42.0
HIE478.N-ILE442.O 42.5
LEU30.N-TYR37.O 42.5
GLN299.NE2-ARG4.O 42.5
ILE384.N-LYS396.O 42.5
ILE78.N-LYS90.O 43.0
ASN401.N-ASP339.O 43.0
SER560.OG-ILE565.O 43.0
LEU395.N-VAL342.O 43.0
SER144.OG-LEU141.O 43.5
VAL91.N-ASP34.O 44.0
LEU115.N-VAL148.O 44.0
ARG437.N-THR441.O 44.5
LEU393.N-CYS344.O 44.5
LEU89.N-VAL36.O 45.0
SER450.OG-LEU447.O 45.0
TYR209.OH-ILE259.O 45.0
LEU167.N-VAL171.O 45.5
ASN439.ND2-GLY501.O 45.5
SER147.OG-SER144.O 46.0
rep5
LEU333.N-VAL326.O 39.5
VAL20.N-LEU27.O 39.5
SER144.OG-LEU141.O 39.5
SER139.OG-GLN605.OE1 40.0
CYS128.N-PHE112.O 40.5
TYR209.OH-ILE259.O 41.0
ARG346.N-CYS391.O 41.0
PHE112.N-CYS128.O 41.0
GLN299.NE2-ARG4.O 41.0
LEU381.N-VAL374.O 41.5
LYS311.NZ-GLU596.OE1 41.5
ARG310.NH1-GLU290.OE1 41.5
LEU30.N-TYR37.O 41.5
TYR515.OH-ILE565.O 41.5
ARG437.N-THR441.O 41.5
ASN401.N-ASP339.O 42.0
SER254.OG-ILE259.O 42.0
TYR343.N-LEU336.O 42.0
LYS88.N-SER81.O 42.5
ASN203.ND2-GLY109.O 43.0
VAL91.N-ASP34.O 43.0
TYR37.N-LEU30.O 43.0
HIE172.N-ILE136.O 43.0
GLN605.NE2-ARG310.O 43.0
SER560.OG-ILE565.O 43.5
TYR54.OH-ASP187.O 43.5
GLY149.N-TYR161.O 43.5
LEU115.N-VAL148.O 44.0
GLY452.N-HIE469.O 44.0
ILE384.N-LYS396.O 44.0
HIE478.N-ILE442.O 44.5
ASN439.ND2-GLY501.O 45.0
CYS434.N-PHE418.O 45.5
LYS5.NZ-GLU290.OE1 45.5
ASN95.N-ASP33.O 46.5
102 2 3C-Like Protease (3CLpro)
2.4 Concluding Remarks
103
Fig. 2.24 The secondary structural graphs for the five sets (each set runs for 200 ns) of MDs of the six models of monomer-apo, monomer-N3, dimer-apo, dimer-N3, dimer-2N3, and dimer-2N3covalent in [340], where from left to right is the six models in turns and from up to down is the five sets of the MDs
Fig. 2.25 The RMSF graphs for the five sets (each set runs for 200 ns) of MDs of the six models of monomer-apo, monomer-N3, dimer-apo, dimer-N3, dimer-2N3, and dimer-2N3-covalent in [340]. The first two columns are for the monomer-apo and monomer-N3, respectively (where from up to down is the five sets of MDs). Then the second five columns (i.e., the five sets of MDs rep1rep5) are for the dimer-apo and dimer-N3 where the five columns up are for dimer-apo and the five columns down are for dimer-N3. And then the last five columns (i.e., the five sets of MDs rep1rep5) are for the dimer-2N3 and dimer-2N3-covalent where the five columns up are for dimer-2N3 and the five columns down are for dimer-2N3-covalent
104
2 3C-Like Protease (3CLpro)
Table 2.24 The MD-SBs of monomeric the SARS-CoV-1-Mpro-1q2w model (denoted as “SARS-CoV-1 monomer”) and the SARS-CoV-2-Mpro-6y2e model (denoted as “SARS-CoV-2 monomer”), where each model has three sets of MD simulations [346] SARS-CoV-1 rep1
rep2
rep3
SARS-CoV-2 rep1
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
rep2
rep3
ASP153-LYS102
ASP153-LYS102
ASP153-ARG298
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP176-LYS180
ASP176-LYS180
ASP176-LYS180
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40 ASP187-HIS41
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP187-HIS41
ASP187-HIS41
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP229-LYS269
ASP229-LYS269
ASP229-LYS269
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP229-LYS269
ASP229-LYS269 ASP245-HIS246
ASP245-HIS246
ASP245-HIS246
ASP263-ARG222
ASP263-ARG222
ASP263-ARG222
ASP263-ARG222
ASP263-ARG222
ASP263-ARG222
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP289-LYS137
ASP289-LYS137
ASP289-LYS137
ASP289-LYS137
ASP289-LYS137
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP245-HIS246
ASP216-ARG279
ASP295-LYS5 ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP48-ARG60
ASP48-ARG60
ASP48-ARG60
ASP48-ARG60
ASP48-ARG60
ASP48-ARG60
ASP48-LYS61
ASP48-LYS61
ASP48-LYS61
ASP48-LYS61
ASP48-LYS61
ASP48-LYS61
ASP56-ARG60
ASP56-ARG60
ASP56-ARG60
ASP56-ARG60
ASP56-ARG60
ASP56-ARG60
ASP92-ARG76
ASP92-ARG76
ASP92-ARG76
ASP92-ARG76
ASP92-ARG76
ASP92-ARG76
GLU14-LYS97
GLU14-LYS97
GLU166-HIS163
GLU166-HIS163
GLU166-HIS172
GLU166-HIS172
GLU166-HIS172
GLU166-HIS172
GLU166-HIS172
GLU166-HIS172
GLU178-ARG105
GLU178-ARG105
GLU178-ARG105
GLU178-LYS180
GLU178-LYS180
GLU178-LYS88
GLU240-HIS246
GLU240-HIS246
GLU240-HIS246
GLU240-HIS246
GLU240-HIS246
GLU270-ARG222
GLU270-ARG222
GLU270-ARG222
GLU270-ARG222
GLU270-ARG222
GLU270-LYS269
GLU270-LYS269
GLU270-LYS269
GLU288-ARG4
GLU288-ARG4
GLU14-LYS97
GLU178-ARG105 GLU178-LYS180 GLU270-ARG222
GLU288-LYS5
GLU288-LYS5
GLU288-LYS5
GLU270-LYS269
GLU270-LYS269
GLU270-LYS269
GLU288-ARG4
GLU288-ARG4
GLU288-ARG4
GLU288-LYS5
GLU288-LYS5
GLU288-LYS5
GLU288-ARG131 GLU288-LYS137 GLU290-ARG4
GLU290-ARG4
GLU290-LYS5
GLU290-LYS5
GLU288-LYS137 GLU290-LYS5
GLU288-LYS137
GLU288-LYS137
GLU290-ARG4
GLU290-ARG4
GLU290-ARG4
GLU290-LYS5
GLU290-LYS5
GLU290-LYS5
GLU290-ARG131
GLU290-ARG131
GLU290-ARG131
GLU290-ARG131
GLU290-ARG131
GLU290-ARG131
GLU290-LYS137
GLU290-LYS137
GLU290-LYS137
GLU290-LYS137
GLU290-LYS137
GLU290-LYS137
GLU305-ARG4
GLU305-ARG4
GLU305-ARG4
GLU55-ARG188
GLU55-ARG188
GLU55-ARG40
GLU55-ARG40
GLU55-ARG40
GLU305-LYS5 GLU305-ARG217
GLU305-ARG217
GLU305-ARG298
GLU305-ARG298
GLU55-ARG40
GLU55-ARG40
GLU55-ARG188 GLU47-ARG60 GLU47-LYS61
GLU55-ARG40
2.4 Concluding Remarks
105
Table 2.25 The MD-SBs of dimer the SARS-CoV-1-Mpro-1q2w model (denoted as “SARS-CoV1 dimer”) and the SARS-CoV-2-Mpro-6y2e model (denoted as “SARS-CoV-2 dimer”), where each model has three sets of MD simulations [346] SARS-CoV-1 rep1
rep2
A:GLU14-B:LYS12
B:GLU14-A:LYS12
B:GLU14-A:LYS12
A:GLU290-B:ARG4
B:GLU290-A:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
B:ASP153-B:ARG298
A:ASP153-A:ARG298
rep3
B:ASP153-B:ARG298
A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS12
B:ASP155-B:LYS12
A:ASP155-A:LYS12
B:ASP155-B:LYS12
A:ASP155-A:LYS12
B:ASP155-B:LYS12
A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP176-A:ARG105
B:ASP176-B:ARG105
B:ASP176-B:LYS180
A:ASP176-A:LYS180
B:ASP176-B:LYS180
A:ASP176-A:LYS180
B:ASP176-B:LYS180
A:ASP176-A:LYS180
A:ASP187-A:ARG188
B:ASP187-B:ARG188
A:ASP187-A:ARG188
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP187-A:HIS41
A:ASP187-A:ARG188
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP197-A:LYS137
B:ASP197-B:LYS137
A:ASP197-A:LYS137
B:ASP197-B:LYS137
A:ASP197-A:LYS137
B:ASP197-B:LYS137
A:ASP216-A:ARG279
B:ASP216-B:ARG279
A:ASP216-A:ARG279
B:ASP216-B:ARG279
A:ASP229-A:LYS269
B:ASP229-B:LYS269
A:ASP229-A:LYS269
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP289-A:LYS137
A:ASP48-A:ARG60 A:ASP56-A:ARG60
A:GLU166-A:HIS172 A:GLU178-A:LYS180
B:ASP229-B:LYS269
A:ASP48-A:ARG188
A:ASP48-A:ARG188 A:ASP56-A:ARG60
B:ASP56-B:ARG60
A:ASP92-A:ARG76
B:ASP92-B:ARG76
A:ASP56-A:ARG60
B:ASP56-B:ARG60
A:ASP92-A:ARG76
B:ASP92-B:ARG76
B:ASP92-B:ARG76
A:GLU166-A:HIS163
A:GLU166-A:HIS163
A:ASP229-A:LYS269
A:ASP48-A:ARG60 B:ASP56-B:ARG60
A:ASP56-A:LYS61 A:ASP92-A:ARG76
B:ASP229-B:LYS269
A:GLU166-A:HIS172
A:GLU166-A:HIS163 A:GLU166-A:HIS172
B:GLU166-B:HIS172
A:GLU178-A:ARG88
B:GLU166-B:HIS172
B:GLU166-B:HIS172
A:GLU178-A:ARG88
B:GLU178-B:ARG88
A:GLU178-A:LYS180
B:GLU178-B:LYS180
B:GLU178-B:ARG88
A:GLU178-A:LYS180
B:GLU178-B:LYS180
A:GLU240-A:HIS246
B:GLU240-B:HIS246
B:GLU178-B:LYS180
A:GLU240-A:HIS246
A:GLU240-A:HIS246
B:GLU240-B:HIS246
A:GLU270-A:ARG222
B:GLU270-B:ARG222
A:GLU270-A:LYS269
B:GLU270-B:LYS269
A:GLU270-A:ARG222
B:GLU270-B:ARG222
A:GLU270-A:LYS269
B:GLU270-B:LYS269
A:GLU288-A:LYS5
B:GLU288-B:LYS5
A:GLU270-A:LYS269
B:GLU270-B:LYS269
B:GLU290-B:ARG131
A:GLU288-A:LYS137
B:GLU240-B:HIS246
A:GLU270-A:ARG222
A:GLU288-A:LYS5
B:GLU288-B:LYS5
A:GLU290-A:ARG131
A:GLU290-A:ARG131
B:GLU290-B:ARG131
A:GLU290-A:LYS137
B:GLU290-B:LYS5
A:GLU288-A:LYS5
B:GLU288-B:LYS5
A:GLU290-A:LYS5
A:GLU290-A:ARG131
B:GLU290-B:ARG131
A:GLU47-A:ARG60
A:GLU290-A:LYS137
B:GLU290-B:LYS137
A:GLU47-A:LYS61
A:GLU290-A:LYS5
B:GLU290-B:LYS5
A:GLU290-A:LYS5
B:GLU270-B:ARG222
B:GLU290-B:LYS5
A:GLU47-A:ARG188 B:GLU290-B:LYS137
A:GLU47-A:ARG60 A:GLU47-A:HIS41
B:GLU47-B:HIS41 A:GLU47-A:ARG60 A:GLU47-A:LYS61 A:GLU55-A:ARG40
B:GLU55-B:ARG40
B:GLU55-B:ARG40
B:GLU55-B:ARG188
B:GLU55-B:ARG188
A:GLU55-A:ARG40
B:GLU55-B:ARG40
A:GLU55-A:ARG60 B:GLU55-B:ARG188
B:ASP187-B:HIS164
B:ASP187-B:HIS164
B:ASP187-B:HIS41
B:ASP187-B:HIS41
B:ASP216-B:ARG217
B:GLU178-B:ARG105
B:ASP56-B:ARG188 B:GLU288-B:ARG131
(continued)
106
2 3C-Like Protease (3CLpro)
Table 2.25 (continued) SARS-CoV-2 rep1
rep2
rep3
A:GLU14-B:LYS12
A:GLU14-B:LYS12
A:GLU14-B:LYS12
B:GLU14-A:LYS12
A:GLU290-B:ARG4
A:GLU290-B:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
B:GLU290-A:ARG4 A:ASP216-B:LYS137
B:GLU290-A:ARG4 A:ASP153-A:ARG298
B:ASP153-B:ARG298
A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS12
B:ASP155-B:LYS12
B:ASP176-B:ARG105
A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP155-A:LYS12
B:ASP155-B:LYS12
A:ASP155-A:LYS12
A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP176-A:ARG105
A:ASP187-A:ARG188
B:ASP187-B:ARG188
A:ASP187-A:ARG188
B:ASP187-B:ARG188
A:ASP187-A:ARG188
B:ASP187-B:ARG188
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP187-A:HIS41
B:ASP187-B:HIS41
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP197-A:LYS137
B:ASP197-B:LYS137
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP197-A:LYS137
B:ASP197-B:LYS137
B:ASP229-B:LYS269
A:ASP197-A:LYS137
A:ASP229-A:LYS269
B:ASP197-B:LYS137
A:ASP216-A:ARG279
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP216-A:ARG217
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP216-A:ARG279
B:ASP216-B:ARG279
A:ASP229-A:LYS269
B:ASP229-B:LYS269
A:ASP289-A:ARG131
B:ASP289-B:ARG131
B:ASP295-B:ARG298
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP289-A:LYS137
B:ASP289-B:LYS137
A:ASP289-A:LYS137 A:ASP295-A:ARG298
A:ASP229-A:LYS269
B:ASP229-B:LYS269
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP48-A:ARG60
B:ASP48-B:ARG60
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP48-A:LYS61
B:ASP48-B:LYS61
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP48-A:ARG60
B:ASP48-B:ARG60
A:ASP56-A:ARG60
B:ASP56-B:ARG60
A:ASP48-A:ARG60
B:ASP48-B:ARG60
A:ASP48-A:LYS61
B:ASP48-B:LYS61
A:ASP92-A:ARG76
B:ASP92-B:ARG76
A:ASP48-A:LYS61
B:ASP48-B:LYS61
A:ASP56-A:ARG60
B:ASP56-B:ARG60
A:GLU166-A:HIS172
B:GLU166-B:HIS172
A:ASP56-A:ARG60
B:ASP56-B:ARG60
A:ASP92-A:ARG76
B:ASP92-B:ARG76
A:GLU178-A:ARG105
A:ASP92-A:ARG76
A:GLU178-A:LYS88 A:GLU240-A:HIS246
B:GLU240-B:HIS246
B:ASP92-B:ARG76
A:GLU166-A:HIS172
B:GLU166-B:HIS172
A:GLU240-A:HIS246
B:GLU240-B:HIS246
A:GLU178-A:ARG105
B:GLU178-B:LYS88
A:GLU270-A:ARG222
B:GLU270-B:ARG222 B:GLU270-B:LYS269
A:GLU270-A:ARG222
B:GLU270-B:ARG222
A:GLU240-A:HIS246
B:GLU240-B:HIS246
A:GLU270-A:LYS269
A:GLU270-A:LYS269
B:GLU270-B:LYS269
A:GLU270-A:ARG222
B:GLU270-B:ARG222
A:GLU288-A:LYS137
A:GLU270-A:LYS269
B:GLU270-B:LYS269
B:GLU288-B:LYS5
A:GLU288-A:LYS137
B:GLU290-B:LYS137
A:GLU290-A:ARG131
A:GLU288-A:LYS137 A:GLU288-A:LYS5 A:GLU290-A:ARG131 A:GLU290-A:LYS137
B:GLU166-B:HIS172
A:GLU166-A:HIS172
A:GLU288-A:LYS5
A:GLU290-A:LYS5
B:GLU290-B:LYS5
A:GLU290-A:LYS137
A:GLU55-A:ARG40
B:GLU55-B:ARG40
A:GLU290-A:LYS5
B:GLU288-B:LYS5
A:GLU288-A:LYS5
B:GLU288-B:LYS5
A:GLU290-A:LYS5
B:GLU290-B:LYS5
A:GLU55-A:ARG40
B:GLU55-B:ARG40 B:ASP187-B:HIS41 B:GLU178-B:ARG105
B:GLU290-B:LYS5
B:GLU290-B:ARG131
B:ASP155-B:LYS102
A:GLU47-A:ARG60
B:GLU290-B:LYS137
B:ASP216-B:ARG217
A:GLU47-A:LYS61
B:GLU55-B:ARG188
B:ASP216-B:ARG279
A:GLU55-A:ARG40
B:GLU55-B:ARG40
THR201.OG1-GLU240.O 60.08
LEU89.N-VAL36.O 51.50
ARG131.N-THR135.O 47.70 THR175.OG1-ASP176.O 47.50 GLY149.N-TYR161.O 46.71 ASP153.N-CYS156.O 46.51 LEU75.N-VAL68.O 46.11
LEU27.N-VAL20.O 45.71 ASN95.N-ASP33.O 45.31 LEU242.N-ASN231.OD1 45.31 VAL18.N-GLY29.O 44.51 GLN83.N-LEU86.O 43.51 TYR37.N-LEU30.O 42.51
ALA173.N-MET165.O 48.10
THR45.OG1-ASP48.OD2 47.70
VAL114.N-TYR126.O 47.50
LEU242.N-ASN231.OD1 47.50
LYS90.N-GLY79.O 45.71
ALA70.N-VAL73.O 45.51
ARG105.NH2-PHE181.O 44.91
SER147.OG-SER144.O 44.71
VAL114.N-TYR126.O 49.70
ARG88.N-SER81.O 48.50
LEU75.N-VAL68.O 48.10
LEU242.N-ASN231.OD1 47.31
GLN189.N-MET49.O 47.11
VAL157.N-LYS100.O 46.91
SER113.N-PHE150.O 46.31
LEU167.N-VAL171.O 45.51
LEU167.N-VAL171.O 50.90
SER144.OG-LEU141.O 48.10 HIS172.N-ILE136.O 47.90
LEU75.N-VAL68.O 46.11 SER123.N-ALA116.O 46.11
ALA70.N-VAL73.O 46.11
ASN95.N-ASP33.O 49.70
LEU167.N-VAL171.O 46.51
GLN19.N-GLN69.O 49.90
ARG88.N-SER81.O 46.91 LYS90.N-GLY79.O 46.51
ARG88.N-SER81.O 49.90
GLN19.N-GLN69.O 49.10
PHE150.N-SER113.O 49.10
ASN203.ND2-ASP289.O 50.70
GLY149.N-TYR161.O 50.30
THR21.N-LEU67.O 50.30
LEU87.N-CYS38.O 51.30
VAL20.N-LEU27.O 48.50 ARG105.NH2-PHE181.O 47.70
VAL157.N-LYS100.O 51.10
VAL20.N-LEU27.O 50.50
LEU89.N-VAL36.O 51.70
SER147.OG-LEU115.O 51.10
TYR37.N-LEU30.O 52.30 LYS88.N-SER81.O 52.10
PHE150.N-SER113.O 49.30 ALA70.N-VAL73.O 48.70
LEU89.N-VAL36.O 52.50
LEU27.N-VAL20.O 52.30
GLN69.N-GLN19.O 52.10
GLN19.N-GLN69.O 50.30
ASN95.N-ASP33.O 51.90
HIS163.N-SER147.O 53.49 VAL36.N-LEU89.O 52.89
VAL157.N-LYS100.O 51.10
GLY146.N-HIS163.O 52.69
LEU87.N-CYS38.O 52.50
VAL36.N-LEU89.O 52.89
THR257.OG1-LEU253.O 54.49 VAL157.N-LYS100.O 53.49
LEU89.N-VAL36.O 54.29 VAL114.N-TYR126.O 51.90
VAL114.N-TYR126.O 56.49 THR135.OG1-ASN133.OD1 55.29
THR257.OG1-LEU253.O 56.89 HIS163.N-SER147.O 54.69
LYS90.N-GLY79.O 52.69
VAL36.N-LEU89.O 55.69
LEU167.N-VAL171.O 55.29
THR257.OG1-LEU253.O 56.69
TYR182.OH-CYS160.O 55.09
THR257.OG1-LEU253.O 60.28
HIS172.N-ILE136.O 56.09
ARG131.N-THR135.O 58.28
ILE136.N-HIS172.O 57.49
TYR182.OH-CYS160.O 58.68 TRP31.N-CYS16.O 56.49
ILE78.N-LYS90.O 60.88 VAL36.N-LEU89.O 58.48 TYR182.OH-CYS160.O 58.08
ILE78.N-LYS90.O 61.88
THR201.OG1-GLU240.O 61.28
SER267.OG-ASP263.O 63.47
TRP31.N-CYS16.O 62.28
HIS163.N-SER147.O 61.88
TRP31.N-CYS16.O 61.88
ILE78.N-LYS90.O 63.47
ILE78.N-LYS90.O 64.67
THR201.OG1-GLU240.O 65.87
TYR182.OH-CYS160.O 61.08
TYR209.OH-ILE259.O 64.27
THR135.OG1-ASN133.OD1 65.87
TYR209.OH-ILE259.O 69.06
SARS-CoV-2 rep1
TYR209.OH-ILE259.O 69.06
rep3
VAL20.N-LEU27.O 59.48
THR201.OG1-GLU240.O 64.27
TRP31.N-CYS16.O 66.07
TYR209.OH-ILE259.O 59.28
rep2
SARS-CoV-1 rep1
LEU75.N-VAL68.O 43.91
HIS163.N-SER147.O 44.51
LEU242.N-ASN231.OD1 45.11
LEU167.N-VAL171.O 45.11
GLN69.N-GLN19.O 47.50
VAL114.N-TYR126.O 47.50
VAL36.N-LEU89.O 47.70
TYR37.N-LEU30.O 48.10
THR21.N-LEU67.O 48.10
ASN95.N-ASP33.O 48.50
LEU89.N-VAL36.O 49.70
TYR118.N-SER121.O 51.30
LEU87.N-CYS38.O 51.90
ASP153.N-CYS156.O 52.10
LYS88.N-SER81.O 53.49
TYR182.OH-CYS160.O 55.89
ILE136.N-HIS172.O 56.69
THR257.OG1-LEU253.O 57.09
GLY149.N-TYR161.O 59.88
ILE78.N-LYS90.O 59.88
TRP31.N-CYS16.O 60.48
THR201.OG1-GLU240.O 62.28
VAL20.N-LEU27.O 63.07
THR135.OG1-ASN133.OD1 64.07
ARG131.N-THR135.O 64.67
SER267.OG-ASP263.O 68.06
TYR209.OH-ILE259.O 69.46
rep2
(continued)
THR199.N-ASN238.O 44.11
LYS90.N-GLY79.O 44.51
VAL20.N-LEU27.O 44.71
GLY109.N-MET130.O 44.91
ALA70.N-VAL73.O 45.51
GLY149.N-TYR161.O 45.71
TYR182.N-GLY174.O 45.71
ASN95.N-ASP33.O 48.30
GLN19.N-GLN69.O 49.50
LEU89.N-VAL36.O 49.50
LEU167.N-VAL171.O 49.90
LEU27.N-VAL20.O 50.50
THR135.OG1-ASN133.OD1 51.30
ASP153.N-CYS156.O 52.30
TYR37.N-LEU30.O 53.69
VAL114.N-TYR126.O 53.89
VAL36.N-LEU89.O 54.09
LEU87.N-CYS38.O 55.69
VAL157.N-LYS100.O 56.49
THR257.OG1-LEU253.O 58.68
HIS163.N-SER147.O 59.48
ILE78.N-LYS90.O 59.48
TRP31.N-CYS16.O 62.67
THR201.OG1-GLU240.O 63.07
TYR182.OH-CYS160.O 63.67
TYR209.OH-ILE259.O 65.67
SER267.OG-ASP263.O 65.67
rep3
Table 2.26 The MD-HBs (with occupancy rates ≥20%) of monomeric the SARS-CoV-1-Mpro-1q2w model (denoted as “SARS-CoV-1 monomer”) and the SARS-CoV-2-Mpro-6y2e model (denoted as “SARS-CoV-2 monomer”), where each model has three sets of MD simulations [346]
2.4 Concluding Remarks 107
GLN192.NE2-VAL186.O 42.12 CYS128.N-PHE112.O 42.12
THR199.N-ASN238.O 39.32 LEU115.N-VAL148.O 39.32
VAL18.N-GLY29.O 44.51
SER123.N-ALA116.O 44.31
TYR37.N-LEU30.O 43.91
LEU75.N-VAL68.O 43.91
THR135.OG1-ASN133.OD1 43.51
CYS22.N-THR25.O 43.31
LEU32.N-THR35.O 42.12
LEU115.N-VAL148.O 41.92
GLN83.N-LEU86.O 41.12
GLN83.N-LEU86.O 44.11
PHE112.N-CYS128.O 44.11
GLN299.N-ASP295.O 44.11
LEU87.N-CYS38.O 43.91
CYS128.N-PHE112.O 43.71
ASN231.N-LEU227.O 43.31
LYS137.N-ALA129.O 43.31
SER123.N-ALA116.O 42.71
LEU27.N-VAL20.O 41.32
LEU205.N-THR201.O 37.52 ILE200.N-ASP289.OD2 37.52
GLY149.N-TYR161.O 40.52
GLN189.N-MET49.O 38.72
THR292.OG1-ASP295.OD1 40.32
TYR37.N-LEU30.O 40.12
GLU14.N-SER10.O 35.73
VAL91.N-ASP34.O 35.53
THR175.OG1-ASP176.O 35.33
LEU30.N-TYR37.O 34.73
THR292.OG1-ASP295.OD2 34.13
THR25.OG1-CYS44.O 34.13
TYR239.N-ALA234.O 33.93
ASN84.ND2-GLU178.O 33.53
ASN95.ND2-TRP31.O 33.33
HIS41.NE2-HIS164.O 32.93
CYS160.N-GLY149.O 32.73
ARG40.NH2-ASP187.OD2 32.53
ASN203.ND2-ASP289.O 32.14
ARG105.NH2-PHE181.O 36.33
ALA70.N-VAL73.O 35.93
TYR182.N-GLY174.O 35.93
LEU268.N-MET264.O 35.73
THR175.OG1-ASP176.O 35.53
THR199.N-ASN238.O 35.13
ALA116.N-GLY124.O 34.33
TYR239.N-ALA234.O 34.13
ALA129.N-LYS137.O 33.93
HIS163.N-SER147.O 33.73
ASN95.ND2-GLY15.O 33.33
CYS160.N-GLY149.O 32.93
ASN84.ND2-GLU178.O 32.93
LEU30.N-TYR37.O 36.53
THR21.N-LEU67.O 36.73
TYR182.N-GLY174.O 36.33
GLY109.N-MET130.O 37.13
GLN192.NE2-VAL186.O 36.53
THR135.OG1-ASN133.OD1 36.73
TYR118.N-SER121.O 36.93
CYS128.N-PHE112.O 36.93
TYR126.N-VAL114.O 38.12
PHE150.N-SER113.O 37.52
CYS160.N-GLY149.O 31.74
ASN95.ND2-TRP31.O 32.14
SER113.OG-GLN127.OE1 32.53
CYS22.N-THR25.O 32.53
THR21.N-LEU67.O 32.93
GLN189.N-MET49.O 32.93
GLY109.N-MET130.O 33.13
TYR182.N-GLY174.O 33.33
HIS80.ND1-ASN63.OD1 33.73
TYR239.N-ALA234.O 34.93
THR45.OG1-ASP48.OD2 35.13
ALA173.N-MET165.O 35.13
TYR54.OH-ASP187.O 35.53
LEU87.N-CYS38.O 36.13
THR175.OG1-ASP176.O 36.73
ASN28.ND2-CYS145.O 37.33
HIS172.N-ILE136.O 37.33
THR199.N-ASN238.O 37.72
ARG131.N-THR135.O 37.52
PHE112.N-CYS128.O 37.33
LEU205.N-THR201.O 38.72
THR198.OG1-GLU240.OE1 38.32
TYR54.OH-ASP187.O 38.12
LEU32.N-THR35.O 38.72
ARG131.NH1-ASP289.OD2 39.12
ASN231.N-LEU227.O 40.72
LEU205.N-THR201.O 40.72
LEU32.N-THR35.O 40.72
TYR118.N-SER121.O 40.32
TYR118.N-SER121.O 39.32
GLY149.N-TYR161.O 39.72
PHE8.N-SER113.OG 39.72
ASN203.ND2-ASP289.O 39.92
GLU14.N-SER10.O 40.12
GLN192.NE2-VAL186.O 40.72
SER147.OG-SER144.O 41.12
ASN231.N-LEU227.O 41.32
TYR126.N-VAL114.O 32.73
LEU67.N-THR21.O 33.13
SER10.OG-GLU14.OE2 33.13
THR292.OG1-ASP295.OD2 33.13
ASN28.ND2-CYS145.O 33.93
THR111.OG1-ASP295.OD2 33.93
ASN95.ND2-TRP31.O 34.73
PHE8.N-SER113.OG 35.53
TYR239.N-ALA234.O 35.93
SER113.OG-GLN127.OE1 37.33
ASN84.ND2-GLU178.O 37.92
GLY109.N-MET130.O 38.12
TYR182.N-GLY174.O 38.12
ILE136.N-HIS172.O 38.52
LEU32.N-VAL35.O 38.92
LEU242.N-ASN231.OD1 39.12
LEU115.N-VAL148.O 39.12
ASN203.ND2-ASP289.O 40.12
GLN83.N-VAL86.O 40.52
PHE150.N-SER113.O 41.12
LYS90.N-GLY79.O 41.52
SER147.OG-SER144.O 41.52
LEU30.N-TYR37.O 41.72
VAL20.N-LEU27.O 42.12
VAL18.N-GLY29.O 42.71
GLN189.N-MET49.O 42.91
ASN231.N-LEU227.O 42.91
VAL91.N-ASP34.O 43.11
GLU14.N-SER10.O 43.31
GLY146.N-HIS163.O 43.51
THR45.OG1-ASP48.OD2 43.71
SARS-CoV-2 rep1 LEU27.N-VAL20.O 44.31
rep3 GLY146.N-HIS163.O 42.32
rep2
ASN95.N-ASP33.O 44.71
SARS-CoV-1 rep1
SER144.OG-LEU141.O 44.31
Table 2.26 (continued) rep2
VAL86.N-GLN83.O 29.94
LEU268.N-MET264.O 30.54
TYR126.N-VAL114.O 31.34
SER158.N-ASN151.O 31.54
SER81.N-LYS88.O 31.74
THR243.OG1-HIS246.ND1 32.14
LYS269.N-CYS265.O 32.14
ALA210.N-ALA206.O 32.34
PHE8.N-SER113.OG 33.53
ILE281.N-SER284.O 33.73
ALA70.N-VAL73.O 33.93
GLN299.NE2-ASP295.O 34.13
SER123.N-ALA116.O 35.13
THR199.N-ASN238.O 35.33
CYS128.N-PHE112.O 35.73
VAL91.N-ASP34.O 35.73
SER147.OG-SER144.O 37.13
LEU32.N-VAL35.O 37.33
ASN203.ND2-ASP289.O 37.52
TYR239.N-ALA234.O 37.92
LYS137.N-ALA129.O 38.52
GLN83.N-VAL86.O 38.72
THR45.OG1-ASP48.OD1 38.92
GLN192.NE2-VAL186.O 39.32
LEU205.N-THR201.O 39.32
ASN231.N-LEU227.O 40.32
PHE112.N-CYS128.O 40.72
GLY109.N-MET130.O 41.12
LEU27.N-VAL20.O 41.52
TYR182.N-GLY174.O 43.11
VAL157.N-LYS100.O 43.11
LYS90.N-GLY79.O 43.51
PHE150.N-SER113.O 43.91
THR175.OG1-ASP176.O 43.91
rep3
THR25.OG1-CYS44.O 32.14
PHE112.N-CYS128.O 32.73
ASN28.ND2-CYS145.O 33.13
THR21.N-LEU67.O 33.53
LEU115.N-VAL148.O 34.13
ALA116.N-GLY124.O 34.13
CYS22.N-THR25.O 34.13
ILE281.N-SER284.O 34.33
LEU30.N-TYR37.O 35.33
THR45.OG1-ASP48.OD2 35.93
ARG131.N-THR135.O 36.53
ASN203.ND2-ASP289.O 37.13
ARG105.NH2-PHE181.O 37.13
GLY146.N-HIS163.O 37.13
ASN95.ND2-TRP31.O 37.52
SER144.OG-LEU141.O 37.52
SER113.OG-GLN127.OE1 38.32
ASN231.N-LEU227.O 38.32
LEU205.N-THR201.O 38.32
PHE8.N-SER113.OG 38.52
LEU32.N-VAL35.O 38.92
GLU14.N-SER10.O 39.52
PHE150.N-SER113.O 40.52
VAL91.N-ASP34.O 40.92
TYR239.N-ALA234.O 40.92
VAL18.N-GLY29.O 41.12
HIS172.N-ILE136.O 41.72
LEU242.N-ASN231.OD1 42.32
GLN83.N-VAL86.O 42.32
THR175.OG1-ASP176.O 42.71
ASN133.ND2-GLY195.O 42.91
LEU75.N-VAL68.O 43.31
CYS128.N-PHE112.O 43.51
LYS88.N-SER81.O 43.91
108 2 3C-Like Protease (3CLpro)
SER62.N-ASN65.OD1 27.15 TRP218.NE1-THR280.O 27.15
ARG131.N-THR135.O 25.55 ARG105.NH1-ASP176.OD1 25.35
SER10.OG-GLU14.OE2 24.35
GLN107.N-GLN110.OE1 24.15
ILE200.N-ASP289.OD1 25.35
VAL91.N-ASP34.O 25.15
ILE200.N-ASP289.OD2 27.15 ALA210.N-ALA206.O 27.15
HIS41.NE2-HIS164.O 25.75 ASN151.N-SER158.O 25.55
GLN192.NE2-VAL186.O 24.95
ASN151.N-SER158.O 24.55
THR292.OG1-ASP295.OD2 25.35
THR198.OG1-GLU240.OE2 25.35
VAL104.N-PHE159.O 27.54 THR198.OG1-GLU240.OE1 27.35
THR292.OG1-ASP295.OD2 26.55 SER254.OG-ILE259.O 25.75
TRP218.NE1-THR280.O 26.35
ILE281.N-SER284.O 25.35
ALA116.N-GLY124.O 25.15
THR198.OG1-GLU240.OE1 25.35
ARG4.NH2-GLU288.OE1 26.55
LYS180.N-ASP176.OD1 25.15
ILE281.N-SER284.O 25.35
GLN19.NE2-ASN28.OD1 26.95 SER113.N-PHE150.O 28.14
ARG105.NH2-PHE181.O 28.94
SER81.N-ARG88.O 27.54
LEU67.N-THR21.O 25.95
ASN151.ND2-THR111.O 26.95 THR198.OG1-GLU240.OE2 26.95
SER10.OG-GLU14.OE1 29.14
LYS180.N-ASP176.OD2 27.74
GLY120.N-ASN28.OD1 26.15
LYS180.N-ASP176.OD2 27.15 ALA173.N-MET165.O 28.94
ARG40.NH2-ASP187.OD2 29.34
LEU67.N-THR21.O 27.74
SER158.N-ASN151.O 26.35
LYS269.N-CYS265.O 27.15
ASN84.ND2-GLU178.O 26.95
THR25.OG1-CYS44.O 29.94
THR98.OG1-ASP33.OD2 27.35
LEU205.N-THR201.O 30.74
ALA116.N-GLY124.O 28.54 SER158.N-ASN151.O 27.94
TYR209.N-LEU205.O 26.55
THR98.OG1-ASP33.OD1 27.74
TYR118.N-SER121.O 30.94
LEU86.N-GLN83.O 28.74
THR292.OG1-ASP295.OD1 26.55
LYS269.N-CYS265.O 26.75
ASN28.ND2-GLY143.O 28.34
SER123.N-ALA116.O 30.94
SER10.OG-GLU14.OE2 28.74
ASN151.N-SER158.O 30.14
TYR126.N-VAL114.O 27.35
SER81.N-ARG88.O 28.74 THR198.OG1-GLU240.OE1 27.94
TYR54.OH-ASP187.O 28.34
ARG131.NH1-ASP289.OD1 29.14
THR199.N-ASN238.O 31.54 CYS160.N-GLY149.O 31.34
ASN231.ND2-LEU242.O 29.94 ILE281.N-SER284.O 29.34
VAL104.N-PHE159.O 28.74
LYS102.N-VAL157.O 28.54
CYS22.N-THR25.O 30.74
ASN231.ND2-LEU242.O 30.14
LEU268.N-MET264.O 31.74 VAL86.N-GLN83.O 31.54
TRP218.NE1-THR280.O 30.74 PHE112.N-CYS128.O 29.94
ARG40.NE-ASP187.OD1 29.54
HIS80.ND1-ASN63.OD1 28.94
ASN133.ND2-GLY195.O 31.14
SER158.N-ASN151.O 31.14
LYS269.N-CYS265.O 32.34 PHE112.N-CYS128.O 32.34 SER158.N-ASN151.O 31.94
VAL91.N-ASP34.O 31.34 LEU268.N-MET264.O 31.34 THR292.OG1-ASP295.OD1 30.74
LEU268.N-MET264.O 30.74
ASN231.ND2-LEU242.O 30.54
ASN28.ND2-CYS145.O 29.94
THR198.OG1-GLU240.OE2 32.34
CYS128.N-PHE112.O 31.54
ILE281.N-SER284.O 32.53
LYS102.N-VAL157.O 31.74
LYS102.N-VAL157.O 32.34
GLY109.N-MET130.O 31.74
CYS300.N-ASP295.O 32.73
SARS-CoV-2 rep1
rep3
PHE8.N-SER113.OG 32.14
PHE8.N-SER113.OG 31.94
GLN19.N-GLN69.O 32.73
HIS172.N-ILE136.O 31.34
rep2
SARS-CoV-1 rep1
ASN84.ND2-GLU178.O 25.55
CYS22.N-THR25.O 25.95
THR292.OG1-ASP295.OD1 26.35
ASN151.N-SER158.O 26.55
SER113.N-PHE150.O 26.55
LYS102.N-VAL157.O 27.15
LEU67.N-THR21.O 27.15
THR21.OG1-THR26.OG1 27.35
ARG105.NH2-PHE181.O 27.74
ALA255.N-GLY251.O 27.74
GLN299.NE2-ARG4.O 27.74
ARG40.NE-ASP187.OD1 27.94
ALA173.N-MET165.O 27.94
TYR209.N-LEU205.O 27.94
ARG60.NH2-ASP48.OD1 28.14
HIS80.ND1-ASN63.OD1 28.34
THR98.OG1-ASP33.OD1 28.34
CYS160.N-GLY149.O 28.54
ARG40.NE-ASP187.OD2 28.74
ASN133.ND2-GLY195.O 28.94
VAL104.N-PHE159.O 28.94
ARG60.NH1-ASP48.OD2 29.14
SER254.OG-ILE259.O 29.14
VAL18.N-GLY29.O 29.34
ALA129.N-LYS137.O 29.74
rep2
(continued)
ARG40.NH2-ASP187.OD2 25.75
SER113.N-PHE150.O 26.15
ASN221.N-SER267.OG 26.55
LEU67.N-THR21.O 28.34
ASN231.ND2-LEU242.O 28.34
GLN299.NE2-ARG4.O 28.34
ARG298.N-PHE294.O 28.94
SER147.OG-SER144.O 29.54
CYS160.N-GLY149.O 30.14
LYS102.N-VAL157.O 30.34
SER123.N-ALA116.O 30.34
TYR54.OH-ASP187.O 30.74
VAL86.N-GLN83.O 30.74
ASN203.ND2-GLY109.O 30.74
TYR118.N-SER121.O 30.74
LYS269.N-CYS265.O 30.94
SER10.OG-GLU14.OE2 30.94
ALA173.N-MET165.O 31.14
THR198.OG1-GLU240.OE2 31.14
LEU268.N-MET264.O 31.34
THR292.OG1-ASP295.OD2 31.34
ILE136.N-HIS172.O 31.54
SER10.OG-GLU14.OE1 31.74
GLN192.NE2-VAL186.O 31.74
TYR126.N-VAL114.O 31.74
rep3
Table 2.27 The MD-HBs (with occupancy rates ≥20%) of monomeric the SARS-CoV-1-Mpro-1q2w model (denoted as “SARS-CoV-1 monomer”) and the SARS-CoV-2-Mpro-6y2e model (denoted as “SARS-CoV-2 monomer”), where each model has three sets of MD simulations [346] (continuation)
2.4 Concluding Remarks 109
THR26.OG1-THR21.OG1 21.36
ARG131.NH2-ASP289.OD1 21.36
LEU208.N-VAL204.O 21.36
ASN28.N-CYS145.O 21.36
ARG105.NH1-ASP176.OD2 20.96
ARG40.NH2-ASP187.OD1 21.56
GLY120.N-GLN19.OE1 21.76
ALA255.N-GLY251.O 20.36
SER254.OG-ILE259.O 21.56
SER301.N-GLY2.O 21.76
GLN83.NE2-GLU178.O 20.96
ARG40.NE-ASP187.OD2 21.76
ARG131.NH2-ASP289.OD2 21.96
SER113.N-PHE150.O 20.96
ASP216.N-ALA211.O 21.76
ALA210.N-ALA206.O 21.96
HIS80.ND1-ASN63.OD1 20.96
THR21.OG1-THR26.OG1 21.96
SER254.OG-ILE259.O 22.36
ARG4.NH1-GLU288.OE2 20.76
ARG217.NH1-ASP216.O 22.75
ASN133.ND2-GLY195.O 22.36
ALA173.N-MET165.O 22.75
LEU30.N-TYR37.O 22.55
TRP218.NE1-THR280.O 23.35
ARG105.NH1-LYS180.O 22.75
ASN95.ND2-TRP31.O 23.15
TYR209.N-LEU205.O 22.95
SER81.N-ARG88.O 23.55
ALA210.N-ALA206.O 23.35
ASN28.ND2-SER147.OG 24.35
LYS5.NZ-ASP295.OD1 24.35
THR292.N-ASP295.OD2 25.75 ASN133.ND2-GLY195.O 25.55
THR21.OG1-THR26.OG1 23.95
HIS164.N-ALA173.O 21.36
MET130.N-GLN110.O 21.96
THR25.OG1-CYS44.O 21.96
ARG131.NH2-ASP289.OD1 22.16
VAL104.N-PHE159.O 22.36
GLN107.N-GLN110.OE1 22.95
VAL186.N-GLN192.OE1 23.15
TYR101.OH-ASP33.OD2 23.15
ALA255.N-GLY251.O 23.35
GLN69.N-GLN19.O 23.35
GLY120.N-ASN28.OD1 23.55
ILE136.N-HIS172.O 23.95
GLN69.N-GLN19.O 21.76 GLN273.N-LYS269.O 21.56
THR292.N-ASP295.OD1 21.96 ASN180.N-ASP176.OD1 21.76
VAL186.N-GLN192.OE1 20.16
ARG131.NH2-ASP289.OD2 21.96
LEU272.N-LEU268.O 20.56 CYS265.N-VAL261.O 20.56 ASN180.N-ASP176.OD1 20.56 SER254.N-LEU250.O 20.36
THR26.OG1-THR21.OG1 20.56 ASN180.N-ASP176.OD2 20.56 LEU272.N-LEU268.O 20.36 ASP216.N-ALA211.O 20.36
ASN28.N-CYS145.O 20.36
ARG131.NH2-ASP289.OD1 20.96 ASN180.N-ASP176.OD2 20.56
ARG298.N-PHE294.O 21.76 TYR54.OH-ASP187.O 21.76 LEU115.N-VAL148.O 21.56
THR21.OG1-THR26.OG1 21.96
GLY120.N-GLN19.OE1 22.55 THR226.OG1-ASP229.OD2 22.36
TYR101.OH-ASP33.OD1 21.36
HIS164.N-ALA173.O 22.16
TRP218.NE1-THR280.O 22.16
TYR209.N-LEU205.O 22.36
MET130.N-GLN110.O 22.75
SER62.N-ASN65.OD1 22.75
SER121.N-TYR118.O 22.75
HIS41.NE2-HIS164.O 23.15
THR243.OG1-HIS246.ND1 23.15
CYS156.N-ASP153.O 23.35
LEU208.N-VAL204.O 23.55
THR292.OG1-ASP295.OD1 23.55
ALA255.N-GLY251.O 23.75
THR111.OG1-ASP295.OD1 24.15
GLY120.N-ASN28.OD1 24.15
SER158.N-ASN151.O 24.35
ASN151.N-SER158.O 24.55
HIS80.ND1-ASN63.OD1 24.55
THR45.OG1-ASP48.OD1 24.75
GLN107.N-GLN110.OE1 24.75
SER254.OG-ILE259.O 24.95
VAL104.N-PHE159.O 25.15
THR198.OG1-GLU240.OE1 25.35
SER81.N-LYS88.O 25.35
GLN189.N-MET49.O 25.55
rep3
ASN180.N-ASP176.OD1 20.16
THR45.OG1-ASP48.OD2 22.75 ARG40.NH2-ASP187.OD1 22.55
ASN274.ND2-GLU270.O 21.36 ALA255.N-GLY251.O 21.36
THR111.OG1-ASP295.OD2 22.95 TYR161.OH-HIS172.ND1 22.95
THR21.N-LEU67.O 21.56
GLN19.NE2-ASN28.OD1 23.35
SER10.OG-GLU14.OE1 23.35
THR198.OG1-GLU240.OE1 23.75
THR98.OG1-ASP33.OD2 23.75
ALA116.N-GLY124.O 23.95
GLY146.N-HIS163.O 23.95
ASN95.ND2-TRP31.O 24.15
ARG40.NH2-ASP187.OD2 24.35
HIS172.N-ILE136.O 24.55
ASN221.N-SER267.OG 24.55
ASN151.ND2-THR111.O 24.55
ILE200.N-ASP289.OD1 24.95
GLU14.N-SER10.O 24.95
ASN231.ND2-LEU242.O 25.15
GLN19.N-GLN69.O 25.15
LEU30.N-TYR37.O 25.15
SER113.OG-GLN127.OE1 25.35
TRP218.NE1-THR280.O 25.55
SER10.OG-GLU14.OE2 25.55
THR198.OG1-GLU240.OE2 25.55
rep2
ARG40.NE-ASP187.OD2 21.36
ARG40.NH2-ASP187.OD1 21.56
ASN231.ND2-LEU242.O 21.56
ASP216.N-ALA211.O 21.76
TYR101.OH-ASP33.OD2 21.96
TYR209.N-LEU205.O 21.96
GLN273.N-LYS269.O 22.55
GLN69.N-GLN19.O 23.55
THR243.OG1-HIS246.ND1 23.75
ALA116.N-GLY124.O 23.75
ASN221.N-SER267.OG 24.15
ASN180.N-ASP176.OD2 24.35
GLN107.N-GLN110.OE1 24.35
LYS102.N-VAL157.O 24.55
SER254.OG-ILE259.O 24.95
ASN203.ND2-GLY109.O 25.15
HIS80.ND1-ASN63.OD1 25.15
SER10.OG-GLU14.OE1 24.35 ALA210.N-ALA206.O 24.15 ALA234.N-PHE230.O 24.15
ALA255.N-GLY251.O 23.55
LEU208.N-VAL204.O 23.55
ALA234.N-PHE230.O 23.55
ALA234.N-PHE230.O 24.35
THR21.OG1-THR26.OG1 24.35
LEU67.N-THR21.O 24.35
ARG131.NE-ASP197.OD2 25.95
LYS269.N-CYS265.O 24.95
SER10.OG-GLU14.OE1 23.75
THR292.N-ASP295.OD1 24.75
SARS-CoV-2 rep1 ARG40.NE-ASP187.OD1 27.15
TYR126.N-VAL114.O 24.95
CYS117.N-GLY143.O 24.95
rep3
rep2
LEU86.N-GLN83.O 24.15
SARS-CoV-1 rep1
Table 2.27 (continued)
110 2 3C-Like Protease (3CLpro)
2.4 Concluding Remarks
111
Table 2.28 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-1-Mpro-1q2w model (denoted as “SARS-CoV-1 dimer”) —the model has three sets of MD simulations [346] SARS-CoV-1 rep1
rep2
rep3
A:TYR118.OH-B:ARG298.O 35.86%
A:SER139.OG-B:GLN299.OE1 54.38%
B:GLN299.NE2-A:SER139.O 47.61%
A:SER139.OG-B:GLY2.O 32.67%
B:VAL125.N-A:ALA7.O 34.46%
B:ARG4.NH1-A:GLU290.OE2 40.84%
A:ALA7.N-B:VAL125.O 28.69%
A:GLY11.N-B:GLU14.OE2 31.47%
A:ARG4.NH2-B:GLU290.OE2 39.04%
A:GLY11.N-B:GLU14.OE2 28.49%
A:VAL125.N-B:ALA7.O 31.27%
A:GLY11.N-B:GLU14.OE2 37.25%
B:ARG4.NH2-A:GLU290.OE1 30.08%
B:ALA7.N-A:VAL125.O 30.88%
A:ALA7.N-B:VAL125.O 32.27%
B:VAL125.N-A:ALA7.O 25.30%
B:ARG4.NH1-A:GLU290.OE1 29.88%
B:ARG4.NH2-A:GLU290.OE1 35.46%
B:ARG4.NH1-A:GLU290.OE2 24.30%
B:ARG4.NH2-A:GLU290.OE2 29.48%
A:TYR118.OH-B:ARG298.O 29.48%
B:GLY11.N-A:GLU14.OE2 23.71%
B:GLY11.N-A:GLU14.OE2 28.49%
A:ARG4.NH1-B:GLU290.OE1 28.29%
B:ARG4.NH2-A:GLU290.OE2 21.31%
A:ARG4.NH1-B:GLU290.OE1 22.51%
A:ARG4.NH2-B:GLU290.OE1 25.10%
A:ARG4.N-B:SER139.OG 20.32%
A:ARG4.NH2-B:GLU290.OE2 21.51%
A:VAL125.N-B:ALA7.O 20.12%
B:GLY11.N-A:GLU14.OE2 23.71% A:VAL125.N-B:ALA7.O 21.12%
A:SER10.OG-A:GLU14.OE2 82.47%
A:SER10.OG-A:GLU14.OE2 85.46%
A:SER10.OG-A:GLU14.OE2 84.46%
A:TYR209.OH-A:ILE259.O 65.94%
A:TRP31.N-A:CYS16.O 66.93%
A:TYR209.OH-A:ILE259.O 69.92%
A:TYR182.OH-A:CYS160.O 64.74%
A:THR201.OG1-A:GLU240.O 65.54%
A:THR201.OG1-A:GLU240.O 66.73%
A:TRP31.N-A:CYS16.O 62.95%
A:TYR182.OH-A:CYS160.O 63.75%
A:TYR182.OH-A:CYS160.O 63.55%
A:THR201.OG1-A:GLU240.O 62.55%
A:TYR209.OH-A:ILE259.O 62.15%
A:ILE78.N-A:LYS90.O 63.35%
A:VAL36.N-A:LEU89.O 60.36%
A:THR257.OG1-A:LEU253.O 59.96%
A:TRP31.N-A:CYS16.O 62.35%
A:HIS163.N-A:SER147.O 59.16%
A:HIS163.N-A:SER147.O 59.96%
A:SER147.OG-A:SER144.O 60.76%
A:SER147.OG-A:SER144.O 59.16%
A:ILE78.N-A:LYS90.O 59.56%
A:HIS163.N-A:SER147.O 60.56%
A:ILE78.N-A:LYS90.O 58.76%
A:VAL36.N-A:LEU89.O 58.37%
A:GLY149.N-A:TYR161.O 60.36%
A:THR257.OG1-A:LEU253.O 56.77%
A:VAL20.N-A:LEU27.O 56.18%
A:LEU115.N-A:VAL148.O 56.77%
A:GLY149.N-A:TYR161.O 56.37%
A:LEU87.N-A:CYS38.O 53.78%
A:VAL36.N-A:LEU89.O 55.18%
A:LEU167.N-A:VAL171.O 53.78%
A:VAL114.N-A:TYR126.O 53.19%
A:PHE150.N-A:SER113.O 53.59%
A:PHE150.N-A:SER113.O 52.99%
A:LEU167.N-A:VAL171.O 52.99%
A:THR257.OG1-A:LEU253.O 53.59%
A:VAL157.N-A:LYS100.O 52.99%
A:LYS90.N-A:GLY79.O 51.59%
A:VAL114.N-A:TYR126.O 51.79%
A:HIS172.N-A:ILE136.O 52.59%
A:GLY146.N-A:HIS163.O 50.80%
A:LEU167.N-A:VAL171.O 51.59%
A:ARG131.N-A:THR135.O 52.59%
A:VAL157.N-A:LYS100.O 49.80%
A:ARG131.N-A:THR135.O 51.59%
A:LEU89.N-A:VAL36.O 51.79%
A:GLN19.N-A:GLN69.O 49.40%
A:LEU89.N-A:VAL36.O 51.20%
A:VAL114.N-A:TYR126.O 51.79%
A:LEU115.N-A:VAL148.O 49.20%
A:LYS90.N-A:GLY79.O 50.60%
A:ASN203.ND2-A:GLY109.O 50.60%
A:SER147.OG-A:SER144.O 48.41%
A:THR135.OG1-A:ASN133.OD1 50.60%
A:GLN192.NE2-A:VAL186.O 50.60%
A:TYR37.N-A:LEU30.O 48.21%
A:LEU87.N-A:CYS38.O 50.40%
A:SER123.N-A:ALA116.O 49.80%
A:ASN203.ND2-A:GLY109.O 48.01%
A:VAL157.N-A:LYS100.O 50.20%
A:THR135.OG1-A:ASN133.OD1 49.80%
A:LEU89.N-A:VAL36.O 47.81%
A:LEU30.N-A:TYR37.O 49.60%
A:LEU115.N-A:VAL148.O 49.20%
A:ARG88.N-A:SER81.O 47.61%
A:GLN19.N-A:GLN69.O 49.00%
A:GLN19.N-A:GLN69.O 48.80%
A:THR135.OG1-A:ASN133.OD1 47.01%
A:SER123.N-A:ALA116.O 47.61%
A:ARG88.N-A:SER81.O 47.81%
A:HIS172.N-A:ILE136.O 46.81%
A:HIS172.N-A:ILE136.O 47.01%
A:LYS90.N-A:GLY79.O 47.61%
A:ASN203.ND2-A:ASP289.O 46.81%
A:TYR37.N-A:LEU30.O 47.01%
A:LEU87.N-A:CYS38.O 47.21%
A:GLY149.N-A:TYR161.O 46.61%
A:ASN95.N-A:ASP33.O 44.42%
A:LEU27.N-A:VAL20.O 47.21%
A:ASN95.N-A:ASP33.O 45.82%
A:PHE8.N-A:SER113.OG 44.22%
A:TYR37.N-A:LEU30.O 46.61%
A:LEU242.N-A:ASN231.OD1 45.22%
A:ASN28.ND2-A:CYS145.O 43.23%
A:LEU242.N-A:ASN231.OD1 46.22%
A:ARG105.NH2-A:PHE181.O 45.02%
A:VAL18.N-A:GLY29.O 43.23%
A:ARG105.NH2-A:PHE181.O 45.22%
A:LEU75.N-A:VAL68.O 44.02%
A:ARG88.N-A:SER81.O 43.23%
A:PHE8.N-A:SER113.OG 45.22%
A:LEU27.N-A:VAL20.O 44.02%
A:SER113.OG-A:GLN127.OE1 42.43%
A:ALA70.N-A:VAL73.O 44.62%
A:ALA70.N-A:VAL73.O 43.82%
A:ALA70.N-A:VAL73.O 42.43%
A:ASN95.N-A:ASP33.O 44.02%
A:GLY109.N-A:MET130.O 43.82%
A:LEU242.N-A:ASN231.OD1 42.03%
A:LEU75.N-A:VAL68.O 43.63%
A:PHE8.N-A:SER113.OG 43.82%
A:GLY146.N-A:HIS163.O 41.83%
A:LEU30.N-A:TYR37.O 42.23%
A:SER123.N-A:ALA116.O 43.43%
A:LEU27.N-A:VAL20.O 41.63%
A:CYS128.N-A:PHE112.O 42.03%
A:PHE150.N-A:SER113.O 42.63%
A:LEU75.N-A:VAL68.O 40.84%
A:ASN231.N-A:LEU227.O 41.83%
A:PHE112.N-A:CYS128.O 41.83%
A:SER144.OG-A:LEU141.O 40.64%
A:GLY146.N-A:HIS163.O 41.24%
A:ARG131.N-A:THR135.O 41.63%
A:SER158.N-A:ASN151.O 40.64%
A:VAL20.N-A:LEU27.O 40.64%
A:VAL18.N-A:GLY29.O 41.63%
A:ARG105.NH2-A:PHE181.O 40.44%
A:VAL18.N-A:GLY29.O 40.64%
A:THR199.N-A:ASN238.O 40.64%
A:ASN203.ND2-A:ASP289.O 40.24%
A:ASN28.ND2-A:CYS145.O 39.84%
A:SER144.OG-A:LEU141.O 39.84%
A:ASN203.ND2-A:GLY109.O 39.84%
A:THR175.OG1-A:ASP176.O 39.44%
A:LEU32.N-A:THR35.O 38.84%
A:LEU205.N-A:THR201.O 39.24%
A:LEU32.N-A:THR35.O 38.84%
A:ASN231.N-A:LEU227.O 38.84%
A:THR199.N-A:ASN238.O 39.04%
A:GLN83.N-A:LEU86.O 38.84%
A:LEU30.N-A:TYR37.O 38.65%
A:LEU32.N-A:THR35.O 38.25%
A:ASN203.ND2-A:ASP289.O 36.25%
A:TYR118.N-A:SER121.O 37.85%
A:ASN231.N-A:LEU227.O 37.85%
A:SER113.OG-A:GLN127.OE1 36.06%
A:ASN95.ND2-A:TRP31.O 37.45%
A:THR175.OG1-A:ASP176.O 37.65%
A:THR198.OG1-A:GLU240.OE2 35.46%
A:ILE281.N-A:SER284.O 37.05%
A:LYS5.NZ-A:GLU290.OE2 36.65%
A:ASN133.ND2-A:GLY195.O 34.86%
A:THR45.OG1-A:HIS41.O 36.45%
A:GLN192.NE2-A:VAL186.O 36.25%
A:ASN95.ND2-A:TRP31.O 34.86%
A:ILE136.N-A:HIS172.O 36.06%
A:TYR239.N-A:ALA234.O 36.06%
A:THR21.N-A:LEU67.O 34.66%
A:ALA7.N-B:VAL125.O 35.86%
A:VAL91.N-A:ASP34.O 35.46%
A:CYS22.N-A:THR25.O 34.46%
A:GLU14.N-A:SER10.O 35.66%
A:LEU268.N-A:MET264.O 35.46%
A:ASN231.ND2-A:LEU242.O 34.06%
A:ARG40.NH2-A:ASP187.OD2 34.86%
A:CYS128.N-A:PHE112.O 35.46%
(continued)
112
2 3C-Like Protease (3CLpro)
Table 2.28 (continued) SARS-CoV-1 rep1
rep2
rep3
A:TYR182.N-A:GLY174.O 33.47%
A:CYS128.N-A:PHE112.O 34.66%
A:PHE112.N-A:CYS128.O 34.26%
A:SER158.N-A:ASN151.O 33.07%
A:THR175.OG1-A:ASP176.O 33.86%
A:ASN95.ND2-A:TRP31.O 34.26%
A:VAL91.N-A:ASP34.O 32.87%
A:ASN28.ND2-A:CYS145.O 33.67%
A:THR292.OG1-A:ASP295.OD2 33.47%
A:GLU14.N-A:SER10.O 32.67%
A:THR21.N-A:LEU67.O 33.67%
A:THR26.OG1-A:THR21.OG1 32.87%
A:ILE281.N-A:SER284.O 32.67%
A:LEU205.N-A:THR201.O 33.47%
A:GLN83.N-A:LEU86.O 32.07%
A:PHE112.N-A:CYS128.O 32.67%
A:GLN83.N-A:LEU86.O 33.47%
A:ASN119.N-A:GLY143.O 32.07%
A:TYR118.N-A:SER121.O 32.27%
A:VAL91.N-A:ASP34.O 33.27%
A:ASN84.ND2-A:GLU178.O 30.68%
A:THR198.OG1-A:GLU240.OE1 31.87%
A:ALA116.N-A:GLY124.O 33.07%
A:THR198.OG1-A:GLU240.OE2 30.48%
A:GLN299.NE2-A:ARG4.O 31.67%
A:SER158.N-A:ASN151.O 32.47%
A:ASN119.ND2-A:THR26.O 30.48%
A:TYR239.N-A:ALA234.O 31.47%
A:THR198.OG1-A:GLU240.OE1 32.07%
A:LEU67.N-A:THR21.O 30.08%
A:LEU268.N-A:MET264.O 31.27%
A:ARG60.NH2-A:GLU47.OE2 31.87%
A:TYR118.N-A:SER121.O 29.68%
A:LEU67.N-A:THR21.O 31.27%
A:ASN84.ND2-A:GLU178.O 31.67%
A:ILE281.N-A:SER284.O 29.68%
A:THR199.N-A:ASN238.O 31.08%
A:ASN231.ND2-A:LEU242.O 31.67%
A:TRP218.NE1-A:THR280.O 29.68%
A:ALA173.N-A:MET165.O 30.08%
A:CYS22.N-A:THR25.O 31.27%
A:ASN133.ND2-A:GLY195.O 29.68%
Table 2.29 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-1-Mpro-1q2w model (denoted as “SARS-CoV-1 dimer”) —the model has three sets of MD simulations [346] (continuation-1) A:SER144.OG-A:LEU141.O 29.68%
A:TYR182.N-A:GLY174.O 30.88%
A:TYR182.N-A:GLY174.O 29.48%
A:ASN214.ND2-A:ALA210.O 29.48%
A:TYR239.N-A:ALA234.O 30.68%
A:GLY109.N-A:MET130.O 29.28%
A:TRP218.NE1-A:THR280.O 29.08%
A:ARG60.NH1-A:GLU47.OE1 30.48%
A:VAL20.N-A:LEU27.O 29.28%
A:SER81.N-A:ARG88.O 28.88%
A:TRP218.NE1-A:THR280.O 30.08%
A:PHE159.N-A:LYS102.O 28.69%
A:THR111.OG1-A:ASP295.OD2 28.29%
A:ARG40.NE-A:ASP187.OD1 29.68%
A:HIS80.ND1-A:ASN63.OD1 28.29%
A:ARG298.NH1-A:MET6.O 28.09%
A:CYS44.N-A:ARG40.O 29.48%
A:ASN231.ND2-A:LEU242.O 28.09%
A:LEU208.N-A:VAL204.O 27.49%
A:SER113.N-A:PHE150.O 29.08%
A:SER81.N-A:ARG88.O 28.09%
A:VAL104.N-A:PHE159.O 27.29%
A:ILE43.N-A:ARG40.O 29.08%
A:ARG40.NH2-A:ASP187.OD1 27.89%
A:GLY109.N-A:MET130.O 27.29%
A:SER81.N-A:ARG88.O 28.88%
A:HIS164.N-A:ALA173.O 27.49%
A:LEU205.N-A:THR201.O 27.09%
A:LYS102.N-A:VAL157.O 28.29%
A:ALA173.N-A:MET165.O 27.49%
A:ASN95.ND2-A:GLY15.O 26.69%
A:ASN133.ND2-A:GLY195.O 28.09%
A:GLU14.N-A:SER10.O 27.09%
A:ALA234.N-A:PHE230.O 26.29%
A:ASN151.ND2-A:THR111.O 28.09%
A:THR21.N-A:LEU67.O 27.09%
A:LYS269.N-A:CYS265.O 26.10%
A:ALA173.N-A:MET165.O 27.89%
A:TYR161.OH-A:HIS172.ND1 26.89%
A:CYS160.N-A:GLY149.O 26.10%
A:LEU268.N-A:MET264.O 27.69%
A:LYS269.N-A:CYS265.O 26.10%
A:ILE136.N-A:HIS172.O 25.70%
A:THR292.OG1-A:ASP295.OD2 26.69%
A:CYS160.N-A:GLY149.O 25.90%
A:HIS164.N-A:ALA173.O 25.70%
A:SER254.OG-A:ILE259.O 26.49%
A:SER113.N-A:PHE150.O 25.50%
A:LYS102.N-A:VAL157.O 25.30%
A:ARG105.NH1-A:ASP176.OD2 26.29%
A:ILE136.N-A:HIS172.O 25.30%
A:LYS5.NZ-A:GLU288.OE2 25.30%
A:LEU67.N-A:THR21.O 25.70%
A:ALA234.N-A:PHE230.O 25.10%
A:LEU86.N-A:GLN83.O 25.10%
A:THR198.OG1-A:GLU240.OE2 25.70%
A:GLN299.NE2-A:VAL296.O 24.50%
A:TYR54.OH-A:ASP187.O 24.90%
A:GLN69.N-A:GLN19.O 24.90%
A:LYS102.N-A:VAL157.O 24.30%
A:SER254.OG-A:ILE259.O 24.90%
A:ARG131.NH2-A:ASP289.OD1 24.90%
A:LYS180.N-A:ASP176.OD1 24.10%
A:THR111.OG1-A:ASP295.OD1 24.90%
A:LYS269.N-A:CYS265.O 24.70%
A:THR198.OG1-A:GLU240.OE1 24.10%
A:PHE159.N-A:LYS102.O 23.90%
A:SER113.OG-A:GLN127.OE1 24.50%
A:ARG40.NH2-A:ASP187.OD2 23.90%
A:LYS180.N-A:ASP176.OD1 23.90%
A:LYS180.N-A:ASP176.OD1 24.50%
A:ARG105.NH1-A:ASP176.OD1 23.11%
A:ASN84.ND2-A:GLU178.O 23.31%
A:LEU208.N-A:VAL204.O 24.50%
A:LEU208.N-A:VAL204.O 22.91%
A:SER113.N-A:PHE150.O 22.71%
A:ALA234.N-A:PHE230.O 24.30%
A:VAL104.N-A:PHE159.O 22.31%
A:LYS5.NZ-A:GLU290.OE1 22.11%
A:ALA255.N-A:GLY251.O 24.30%
A:LYS180.N-A:ASP176.OD2 22.31%
A:ARG105.NH1-A:ASP176.OD2 21.51%
A:GLN192.NE2-A:VAL186.O 23.90%
A:SER254.OG-A:ILE259.O 21.51%
A:ASN151.N-A:SER158.O 21.31%
A:ASN214.ND2-A:ALA210.O 23.71%
A:LEU86.N-A:GLN83.O 21.51%
A:HIS80.ND1-A:ASN63.OD1 20.92%
A:ARG40.NH2-A:ASP187.OD1 22.91%
A:GLN273.N-A:LYS269.O 21.91%
A:ASN151.ND2-A:THR111.O 20.92%
A:LYS5.NZ-A:GLU290.OE1 22.71%
A:ARG105.NH1-A:ASP176.OD2 21.31%
A:ASN274.N-A:GLU270.O 20.52%
A:SER254.N-A:LEU250.O 22.71%
A:ARG131.NH2-A:ASP289.OD1 21.31%
A:TYR209.N-A:LEU205.O 20.52%
A:THR26.OG1-A:THR21.OG1 22.51%
A:TYR101.OH-A:ASP33.OD2 21.31%
A:LYS5.NZ-A:GLU290.OE2 20.52%
A:GLN107.N-A:GLN110.OE1 22.51%
A:GLN83.NE2-A:GLU178.O 20.92%
A:ALA255.N-A:GLY251.O 20.32%
A:THR292.OG1-A:ASP295.OD1 22.31%
A:ALA116.N-A:GLY124.O 20.72%
A:THR292.OG1-A:ASP295.OD2 20.32%
A:LEU86.N-A:GLN83.O 22.31%
A:TYR209.N-A:LEU205.O 20.72%
A:GLN273.N-A:LYS269.O 20.32%
A:VAL104.N-A:PHE159.O 22.11%
A:ARG40.NE-A:ASP187.OD1 20.72%
A:LYS180.N-A:ASP176.OD2 20.32%
A:GLY120.N-A:ASN28.OD1 21.51%
A:ASN221.ND2-A:PHE223.O 20.52%
A:GLN83.NE2-A:GLU178.O 20.12%
A:ARG131.NH2-A:ASP289.OD2 21.31%
A:LYS5.NZ-A:GLU288.OE2 20.32%
A:ASN95.ND2-A:GLY15.O 21.31%
A:ASP92.N-A:ARG76.O 20.32%
B:SER10.OG-B:GLU14.OE2 82.87%
A:CYS160.N-A:GLY149.O 21.31%
A:THR45.OG1-A:HIS41.O 20.12%
B:TYR209.OH-B:ILE259.O 67.53%
A:THR111.OG1-A:ASP295.OD1 21.31%
(continued)
2.4 Concluding Remarks
113
Table 2.29 (continued) B:TYR54.OH-B:ASP187.O 66.33%
A:ILE213.N-A:TYR209.O 21.31%
B:SER10.OG-B:GLU14.OE2 85.26%
B:HIS163.N-B:SER147.O 64.94%
A:PHE159.N-A:LYS102.O 20.92%
B:TYR54.OH-B:ASP187.O 73.90%
B:THR201.OG1-B:GLU240.O 64.34%
A:THR21.OG1-A:THR26.OG1 20.92%
B:TYR209.OH-B:ILE259.O 68.33%
B:TYR182.OH-B:CYS160.O 63.94%
A:THR98.OG1-A:ASN95.O 20.72%
B:ARG40.NH2-B:ASP187.OD1 67.33%
B:TRP31.N-B:CYS16.O 63.75%
A:TYR101.OH-A:ASP33.OD2 20.72%
B:THR201.OG1-B:GLU240.O 63.75%
B:SER147.OG-B:SER144.O 61.55%
A:ARG40.NE-A:ASP187.OD2 20.52%
B:SER147.OG-B:SER144.O 63.15%
B:VAL36.N-B:LEU89.O 60.76%
A:TRP207.N-A:ASN203.O 20.32%
B:TRP31.N-B:CYS16.O 62.55%
B:ILE78.N-B:LYS90.O 58.76%
A:ARG4.NH2-B:GLU290.OE1 20.12%
B:ILE78.N-B:LYS90.O 60.76%
B:THR257.OG1-B:LEU253.O 57.97%
A:LYS5.NZ-A:GLU288.OE1 20.12%
B:TYR182.OH-B:CYS160.O 59.16%
B:LEU89.N-B:VAL36.O 55.58%
B:THR135.OG1-B:ASN133.OD1 58.96%
B:LEU115.N-B:VAL148.O 53.59%
B:SER10.OG-B:GLU14.OE2 84.46%
B:HIS163.N-B:SER147.O 58.76%
B:LEU87.N-B:CYS38.O 52.59%
B:TYR209.OH-B:ILE259.O 66.33%
B:VAL114.N-B:TYR126.O 57.97%
B:VAL157.N-B:LYS100.O 52.59%
B:SER147.OG-B:SER144.O 65.14%
B:THR257.OG1-B:LEU253.O 56.77%
B:LEU167.N-B:VAL171.O 51.99%
B:TRP31.N-B:CYS16.O 63.75%
B:ARG131.N-B:THR135.O 53.98%
B:THR135.OG1-B:ASN133.OD1 50.80%
B:ILE78.N-B:LYS90.O 63.35%
B:GLY149.N-B:TYR161.O 53.98%
B:VAL114.N-B:TYR126.O 50.00%
B:THR201.OG1-B:GLU240.O 62.95%
B:THR25.OG1-B:CYS44.O 53.78%
B:GLN19.N-B:GLN69.O 49.40%
B:THR257.OG1-B:LEU253.O 58.17%
B:LEU87.N-B:CYS38.O 53.39%
B:VAL20.N-B:LEU27.O 49.00%
B:HIS163.N-B:SER147.O 57.37%
B:ARG40.NE-B:ASP187.OD2 53.39%
B:GLY146.N-B:HIS163.O 48.41%
B:LEU167.N-B:VAL171.O 56.97%
B:LEU167.N-B:VAL171.O 53.39%
B:TYR37.N-B:LEU30.O 48.01%
B:TYR54.OH-B:ASP187.O 56.77%
B:PHE112.N-B:CYS128.O 51.59%
B:ARG88.N-B:SER81.O 48.01%
B:LEU115.N-B:VAL148.O 56.57%
B:VAL36.N-B:LEU89.O 51.39%
B:PHE150.N-B:SER113.O 47.61%
B:TYR182.OH-B:CYS160.O 55.38%
B:PHE150.N-B:SER113.O 50.40%
B:LEU75.N-B:VAL68.O 46.22%
B:THR25.OG1-B:CYS44.O 53.78%
B:GLN19.N-B:GLN69.O 50.20%
B:LYS90.N-B:GLY79.O 46.22%
B:VAL36.N-B:LEU89.O 53.78%
B:ASN95.N-B:ASP33.O 49.80%
B:ASN95.N-B:ASP33.O 46.22%
B:GLY109.N-B:MET130.O 53.59%
B:VAL20.N-B:LEU27.O 49.60%
B:ALA70.N-B:VAL73.O 45.82%
B:LEU87.N-B:CYS38.O 52.99%
B:ASN203.ND2-B:GLY109.O 48.61%
B:PHE112.N-B:CYS128.O 45.42%
B:VAL157.N-B:LYS100.O 52.59%
B:PHE8.N-B:SER113.OG 48.41%
B:GLY109.N-B:MET130.O 44.62%
B:LEU27.N-B:VAL20.O 51.99%
B:LEU242.N-B:ASN231.OD1 47.81%
B:HIS172.N-B:ILE136.O 44.62%
B:VAL20.N-B:LEU27.O 51.59%
B:LEU75.N-B:VAL68.O 47.21%
B:LEU27.N-B:VAL20.O 44.42%
B:ARG40.NH2-B:ASP187.OD1 51.39%
B:CYS22.N-B:THR25.O 47.21%
B:GLY149.N-B:TYR161.O 42.43%
B:GLY146.N-B:HIS163.O 49.80%
B:ASN203.ND2-B:ASP289.O 46.61%
B:LEU32.N-B:THR35.O 42.03%
B:GLY149.N-B:TYR161.O 49.80%
B:ASN133.ND2-B:GLY195.O 46.41%
B:SER123.N-B:ALA116.O 41.43%
B:GLN299.NE2-B:ARG4.O 48.21%
B:VAL157.N-B:LYS100.O 45.62%
B:PHE8.N-B:SER113.OG 41.04%
B:GLN19.N-B:GLN69.O 47.81%
B:LYS90.N-B:GLY79.O 45.22%
B:VAL18.N-B:GLY29.O 40.64%
B:VAL114.N-B:TYR126.O 47.41%
B:SER123.N-B:ALA116.O 44.62%
B:LEU242.N-B:ASN231.OD1 40.44%
B:ALA70.N-B:VAL73.O 47.41%
B:LEU27.N-B:VAL20.O 44.22%
B:TYR182.N-B:GLY174.O 40.24%
B:LYS90.N-B:GLY79.O 47.21%
B:ALA70.N-B:VAL73.O 44.22%
B:CYS128.N-B:PHE112.O 39.64%
B:HIS172.N-B:ILE136.O 46.22%
B:ASN231.N-B:LEU227.O 44.02%
114
2 3C-Like Protease (3CLpro)
Table 2.30 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-1-Mpro-1q2w model (denoted as “SARS-CoV-1 dimer”) —the model has three sets of MD simulations [346] (continuation-2) B:ASN133.ND2-B:GLY195.O 39.44%
B:SER123.N-B:ALA116.O 46.02%
B:VAL18.N-B:GLY29.O 43.82%
B:TYR118.N-B:SER121.O 39.44%
B:ASN95.N-B:ASP33.O 44.82%
B:LEU205.N-B:THR201.O 43.43%
B:GLN299.NE2-B:ARG4.O 39.44%
B:LEU75.N-B:VAL68.O 44.02%
B:LEU32.N-B:THR35.O 43.03%
B:ARG131.N-B:THR135.O 39.24%
B:ARG88.N-B:SER81.O 44.02%
B:LEU115.N-B:VAL148.O 42.03%
B:ARG105.NH2-B:PHE181.O 38.84%
B:PHE150.N-B:SER113.O 43.63%
B:TYR118.N-B:SER121.O 41.83%
B:ASN84.ND2-B:GLU178.O 38.84%
B:ARG105.NH2-B:PHE181.O 43.43%
B:ARG88.N-B:SER81.O 41.43%
B:ASN28.ND2-B:CYS145.O 38.65%
B:LEU89.N-B:VAL36.O 42.43%
B:ASN28.ND2-B:CYS145.O 41.43%
B:THR199.N-B:ASN238.O 37.85%
B:TYR118.N-B:SER121.O 42.23%
B:ASN51.ND2-B:ASN53.O 40.24%
B:ALA173.N-B:MET165.O 37.25%
B:PHE8.N-B:SER113.OG 41.43%
B:LEU89.N-B:VAL36.O 39.84%
B:ASN231.N-B:LEU227.O 37.05%
B:ASN203.ND2-B:ASP289.O 41.24%
B:TYR37.N-B:LEU30.O 39.64%
B:LEU30.N-B:TYR37.O 36.65%
B:LEU205.N-B:THR201.O 40.84%
B:ALA173.N-B:MET165.O 38.84%
B:THR292.OG1-B:ASP295.OD2 36.06%
B:ARG40.NE-B:ASP187.OD2 40.44%
B:THR111.OG1-B:ASP295.OD1 37.65%
B:ASN203.ND2-B:ASP289.O 36.06%
B:CYS22.N-B:THR25.O 40.04%
B:THR199.N-B:ASN238.O 37.45%
B:ASN203.ND2-B:GLY109.O 35.86%
B:CYS128.N-B:PHE112.O 39.64%
B:SER113.OG-B:GLN127.OE1 36.85%
B:ILE200.N-B:ASP289.OD1 35.46%
B:TYR37.N-B:LEU30.O 39.24%
B:GLY146.N-B:HIS163.O 36.85%
B:SER158.N-B:ASN151.O 35.26%
B:ALA173.N-B:MET165.O 39.24%
B:LEU30.N-B:TYR37.O 36.65%
B:LEU205.N-B:THR201.O 34.66%
B:THR21.N-B:LEU67.O 38.65%
B:ASN214.ND2-B:ALA210.O 36.65%
B:THR175.OG1-B:ASP176.O 33.47%
B:LEU32.N-B:THR35.O 38.45%
B:SER158.N-B:ASN151.O 36.06%
B:TYR239.N-B:ALA234.O 32.47%
B:ASN28.ND2-B:CYS145.O 38.05%
B:THR292.OG1-B:ASP295.OD1 35.06%
B:LEU268.N-B:MET264.O 32.27%
B:SER113.OG-B:GLN127.OE1 36.65%
B:TYR239.N-B:ALA234.O 34.66%
B:GLN83.N-B:LEU86.O 32.07%
B:PHE112.N-B:CYS128.O 36.45%
B:THR21.N-B:LEU67.O 34.46%
B:ILE281.N-B:SER284.O 31.67%
B:SER144.OG-B:LEU141.O 35.66%
B:THR198.OG1-B:GLU240.OE2 33.86%
B:ARG40.NH2-B:ASP187.OD1 31.47%
B:ASP153.N-B:CYS156.O 35.06%
B:HIS80.ND1-B:ASN63.OD1 33.47%
B:ASN95.ND2-B:TRP31.O 31.27%
B:ALA116.N-B:GLY124.O 35.06%
B:ASN95.ND2-B:TRP31.O 33.07%
B:THR292.OG1-B:ASP295.OD1 31.08%
B:GLN83.N-B:LEU86.O 34.06%
B:LYS5.NZ-B:GLU290.OE1 32.67%
B:THR198.OG1-B:GLU240.OE2 30.88%
B:ILE281.N-B:SER284.O 33.86%
B:ILE136.N-B:HIS172.O 31.67%
B:THR21.N-B:LEU67.O 30.88%
B:ILE136.N-B:HIS172.O 33.86%
B:GLY109.N-B:MET130.O 31.27%
B:ASN231.ND2-B:LEU242.O 30.28%
B:THR199.N-B:ASN238.O 33.67%
B:GLN83.N-B:LEU86.O 31.08%
B:VAL91.N-B:ASP34.O 29.88%
B:GLU14.N-B:SER10.O 33.47%
B:GLU14.N-B:SER10.O 30.88%
B:CYS22.N-B:THR25.O 29.88%
B:GLN192.NE2-B:GLY183.O 33.27%
B:CYS160.N-B:GLY149.O 30.68%
B:GLU14.N-B:SER10.O 29.88%
B:VAL18.N-B:GLY29.O 32.87%
B:HIS172.N-B:ILE136.O 30.68%
B:LEU67.N-B:THR21.O 29.68%
B:ARG131.NH2-B:ASP289.OD2 32.67%
B:VAL91.N-B:ASP34.O 30.48%
B:ALA116.N-B:GLY124.O 29.28%
B:LEU30.N-B:TYR37.O 32.27%
B:LEU268.N-B:MET264.O 29.48%
B:THR111.OG1-B:ASP295.OD2 28.49%
B:TYR182.N-B:GLY174.O 32.07%
B:TRP218.NE1-B:THR280.O 29.48%
B:TRP218.NE1-B:THR280.O 27.89%
B:ASN95.ND2-B:TRP31.O 32.07%
B:ASN231.ND2-B:LEU242.O 29.48%
B:LYS102.N-B:VAL157.O 27.29%
B:LEU268.N-B:MET264.O 31.27%
B:ALA116.N-B:GLY124.O 29.28%
B:GLN69.N-B:GLN19.O 26.49%
B:SER158.N-B:ASN151.O 30.88%
B:CYS128.N-B:PHE112.O 29.28%
B:HIS80.ND1-B:ASN63.OD1 26.29%
B:ASN84.ND2-B:GLU178.O 30.28%
B:SER81.N-B:ARG88.O 29.08%
B:GLN192.NE2-B:VAL186.O 25.90%
B:THR111.OG1-B:ASP295.OD1 30.08%
B:ILE281.N-B:SER284.O 28.69%
B:LEU208.N-B:VAL204.O 25.90%
B:THR111.OG1-B:ASP295.OD2 29.88%
B:LYS269.N-B:CYS265.O 28.09%
B:SER254.OG-B:ILE259.O 25.70%
B:ILE106.N-B:TYR182.OH 29.68%
B:THR175.OG1-B:ASP176.O 27.89%
B:GLY120.N-B:ASN28.OD1 25.50%
B:TYR239.N-B:ALA234.O 29.68%
B:SER1.OG-B:ASP216.OD2 27.49%
B:VAL104.N-B:PHE159.O 25.10%
B:ASN214.ND2-B:ALA210.O 29.48%
B:THR198.OG1-B:GLU240.OE1 27.29%
B:LYS269.N-B:CYS265.O 24.70%
B:CYS160.N-B:GLY149.O 28.49%
B:ASN84.ND2-B:GLU178.O 26.89%
B:SER81.N-B:ARG88.O 24.30%
B:ALA234.N-B:PHE230.O 28.49%
B:ASN95.ND2-B:GLY15.O 26.69%
B:CYS160.N-B:GLY149.O 24.30%
B:SER81.N-B:ARG88.O 28.09%
B:THR292.N-B:ASP295.OD1 26.69%
B:SER144.OG-B:CYS117.O 24.30%
B:SER254.OG-B:ILE259.O 28.09%
B:LEU208.N-B:VAL204.O 25.70%
B:ARG40.NE-B:ASP187.OD2 23.71%
B:LYS269.N-B:CYS265.O 27.89%
B:GLN83.NE2-B:GLU178.O 25.30%
B:VAL186.N-B:GLN192.OE1 23.31%
B:ASN231.N-B:LEU227.O 27.69%
B:GLN69.N-B:GLN19.O 24.90%
B:ARG40.NH2-B:ASP187.OD2 22.91%
B:ASN151.ND2-B:THR111.O 27.69%
B:TYR182.N-B:GLY174.O 24.50%
B:LEU141.O-B:SER144.OG 22.71%
B:LYS180.N-B:ASP176.OD2 27.69%
B:LYS102.N-B:VAL157.O 24.10%
B:SER144.OG-B:LEU141.O 22.71%
B:ASN51.ND2-B:ASN53.O 27.69%
B:GLN189.NE2-B:LEU50.O 23.71%
B:ALA234.N-B:PHE230.O 22.71%
B:LEU242.N-B:ASN231.OD1 27.29%
B:ALA234.N-B:PHE230.O 23.51%
B:CYS300.N-B:VAL296.O 22.71%
B:HIS80.ND1-B:ASN63.OD1 27.29%
B:VAL104.N-B:PHE159.O 23.31%
B:ALA255.N-B:GLY251.O 22.51%
B:ASN203.ND2-B:GLY109.O 26.49%
B:PHE159.N-B:LYS102.O 23.11%
B:TYR209.N-B:LEU205.O 22.31%
B:VAL91.N-B:ASP34.O 26.10%
B:LEU86.N-B:GLN83.O 22.91%
B:THR198.OG1-B:GLU240.OE1 22.31%
B:THR175.OG1-B:ASP176.O 25.70%
B:SER1.OG-B:ASP216.OD1 22.91%
B:ALA210.N-B:ALA206.O 22.11%
B:ARG131.NE-B:ASP289.OD1 25.70%
B:GLN107.N-B:GLN110.OE1 22.31%
B:THR25.OG1-B:CYS44.O 22.11%
B:GLN69.N-B:GLN19.O 25.30%
B:LEU67.N-B:THR21.O 22.31%
B:ARG131.NH2-B:ASP289.OD1 22.11%
B:THR21.OG1-B:THR26.OG1 25.30%
B:SER254.OG-B:ILE259.O 21.91%
B:GLN107.N-B:GLN110.OE1 21.91%
B:ASN95.ND2-B:GLY15.O 24.10%
B:HIS41.NE2-B:HIS164.O 21.91%
B:ARG105.NH1-B:LYS180.O 21.91%
B:ARG4.N-B:GLN299.OE1 24.10%
B:VAL186.N-B:GLN192.OE1 21.71%
B:LYS180.N-B:ASP176.OD2 21.71%
B:GLN192.N-B:PRO184.O 24.10%
B:LYS180.N-B:ASP176.OD2 21.31%
(continued)
2.4 Concluding Remarks
115
Table 2.30 (continued) B:LEU58.N-B:TYR54.O 21.71%
B:LYS102.N-B:VAL157.O 23.71%
B:ASP216.N-B:ALA211.O 21.12%
B:TYR101.OH-B:ASP33.OD2 21.51%
B:ARG105.NH1-B:ASP176.OD1 23.71%
B:ARG298.NH2-B:ASP295.OD2 20.92%
B:GLN299.NE2-B:ASP295.O 21.51%
B:ALA255.N-B:GLY251.O 23.51%
B:THR21.OG1-B:THR26.OG1 20.72%
B:THR98.OG1-B:ASN95.O 21.31%
B:LEU67.N-B:THR21.O 22.91%
B:THR98.OG1-B:ASN95.O 20.52%
B:ASN95.ND2-B:GLY15.O 21.31%
B:HIS134.N-B:ARG131.O 22.91%
B:SER113.N-B:PHE150.O 20.52%
B:THR111.OG1-B:ASP295.OD1 21.12%
B:LEU86.N-B:GLN83.O 22.11%
B:GLN192.NE2-B:VAL186.O 20.52%
B:ASP92.N-B:ARG76.O 20.92%
B:SER113.N-B:PHE150.O 22.11%
B:ASN51.N-B:TYR54.OH 20.52%
B:ARG105.NH1-B:ASP176.OD1 20.72%
B:ILE200.N-B:ASP289.OD1 21.91%
B:ASN151.N-B:SER158.O 20.32%
B:ARG131.NH1-B:ASP289.OD1 20.52%
B:ASN151.N-B:SER158.O 21.71%
B:LYS5.NZ-B:GLU288.OE1 20.12%
B:THR45.N-B:ASN51.OD1 20.52%
B:GLN273.N-B:LYS269.O 21.71%
B:SER113.N-B:PHE150.O 20.52%
B:SER139.N-B:TYR126.OH 21.31%
B:MET130.N-B:GLN110.O 20.32%
B:PHE159.N-B:LYS102.O 20.92%
B:ARG40.NE-B:ASP187.OD1 20.12%
B:TYR101.OH-B:ASP33.OD1 20.52% B:THR196.OG1-B:THR198.OG1 20.52% B:LYS5.NZ-B:GLU288.OE2 20.32% B:SER254.N-B:LEU250.O 20.12%
Table 2.31 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-2-Mpro-6y2e model (denoted as “SARS-CoV-2 dimer”) —the model has three sets of MD simulations [346] SARS-CoV-2 rep1
rep2
rep3
A:SER10.OG-A:GLU14.OE2 82.87%
B:SER139.OG-A:GLN299.OE1 64.34%
B:SER139.OG-A:GLN299.OE1 60.76%
A:SER267.OG-A:ASP263.O 65.94%
A:SER139.OG-B:GLN299.OE1 54.58%
A:SER139.OG-B:GLN299.OE1 48.80%
A:SER139.OG-B:GLN299.OE1 52.79%
B:ARG4.NH1-A:GLU290.OE2 50.00%
B:ARG4.NH1-A:GLU290.OE2 43.03%
B:SER139.OG-A:GLN299.OE1 46.02%
B:ARG4.NH2-A:GLU290.OE1 41.24%
B:ARG4.NH2-A:GLU290.OE1 33.67%
A:SER123.OG-B:VAL303.O 26.49%
B:VAL125.N-A:ALA7.O 34.06%
B:GLY11.N-A:GLU14.OE2 30.28%
B:SER1.OG-A:GLU166.OE2 29.08%
B:GLY11.N-A:GLU14.OE2 28.09%
A:GLY11.N-B:GLU14.OE2 30.08%
B:GLY11.N-A:GLU14.OE2 24.50%
B:SER1.OG-A:GLU166.OE1 23.90%
A:ARG4.NH2-B:GLU290.OE1 27.89%
B:SER1.OG-A:GLU166.OE1 24.10%
B:ASN119.ND2-A:PHE305.O 23.90%
A:VAL125.N-B:ALA7.O 26.10%
B:ARG4.NH1-A:GLU290.OE2 20.92%
A:ARG4.NH2-B:GLU290.OE1 22.51%
B:SER1.OG-A:GLU166.OE2 22.51%
B:SER1.N-A:PHE140.O 20.12%
B:SER1.OG-A:GLU166.OE2 21.71%
A:SER1.OG-B:GLU166.OE1 21.12%
B:PHE305.N-A:PRO122.O 21.12% A:TYR54.OH-A:ASP187.O 65.74%
A:ALA7.N-B:VAL125.O 20.92%
A:SER10.OG-A:GLU14.OE2 84.66%
A:TYR182.OH-A:CYS160.O 64.14%
A:PHE140.N-B:SER1.O 20.32%
A:SER267.OG-A:ASP263.O 66.33%
A:TYR209.OH-A:ILE259.O 63.94%
A:ARG4.NH1-B:GLU290.OE2 20.12%
A:TRP31.N-A:CYS16.O 60.96%
A:TRP31.N-A:CYS16.O 63.94% A:ILE78.N-A:LYS90.O 63.75%
A:ILE78.N-A:LYS90.O 59.96%
A:SER10.OG-A:GLU14.OE2 85.06%
A:THR201.OG1-A:GLU240.O 63.55%
A:THR201.OG1-A:GLU240.O 57.57%
A:SER267.OG-A:ASP263.O 69.12%
A:THR135.OG1-A:ASN133.OD1 60.76%
A:SER123.N-A:ALA116.O 57.17%
A:TYR182.OH-A:CYS160.O 66.14%
A:VAL114.N-A:TYR126.O 60.36%
A:HIS163.N-A:SER147.O 55.98%
A:ILE78.N-A:LYS90.O 64.14%
A:SER147.OG-A:SER144.O 60.16%
A:VAL36.N-A:LEU89.O 55.18%
A:TRP31.N-A:CYS16.O 63.35%
A:TYR182.OH-A:CYS160.O 59.96%
A:GLY146.N-A:HIS163.O 54.18%
A:TYR209.OH-A:ILE259.O 61.75%
A:LEU89.N-A:VAL36.O 57.37%
A:VAL114.N-A:TYR126.O 54.18%
A:THR135.OG1-A:ASN133.OD1 56.57%
A:THR257.OG1-A:LEU253.O 56.77%
A:VAL20.N-A:LEU27.O 53.59%
A:THR201.OG1-A:GLU240.O 56.37%
A:LEU27.N-A:VAL20.O 55.58%
A:THR257.OG1-A:LEU253.O 53.39%
A:GLY149.N-A:TYR161.O 55.78%
A:TYR209.OH-A:ILE259.O 54.98%
A:LEU87.N-A:CYS38.O 52.79%
A:GLY146.N-A:HIS163.O 55.18%
A:GLN19.N-A:GLN69.O 53.59%
A:TYR37.N-A:LEU30.O 51.99%
A:VAL36.N-A:LEU89.O 53.78%
A:GLY146.N-A:HIS163.O 52.59%
A:ASP153.N-A:CYS156.O 51.00%
A:LYS88.N-A:SER81.O 52.99%
A:HIS163.N-A:SER147.O 52.39%
A:GLY149.N-A:TYR161.O 50.80%
A:LEU167.N-A:VAL171.O 51.99%
A:TYR182.N-A:GLY174.O 51.59%
A:GLN299.NE2-A:ARG4.O 50.80%
A:LEU89.N-A:VAL36.O 51.79%
A:VAL36.N-A:LEU89.O 51.59%
A:ALA70.N-A:VAL73.O 50.20%
A:GLY109.N-A:MET130.O 51.59%
A:LEU87.N-A:CYS38.O 51.20%
A:SER147.OG-A:SER144.O 49.80%
A:HIS163.N-A:SER147.O 51.39%
A:TYR37.N-A:LEU30.O 50.60%
A:LEU27.N-A:VAL20.O 49.40%
A:VAL20.N-A:LEU27.O 50.20%
A:ASN95.N-A:ASP33.O 49.20%
A:LEU242.N-A:ASN231.OD1 48.80%
A:LEU27.N-A:VAL20.O 50.00%
A:GLY109.N-A:MET130.O 48.01%
A:GLN19.N-A:GLN69.O 48.41%
A:SER123.N-A:ALA116.O 50.00%
A:GLN299.NE2-A:ARG4.O 47.81%
A:ASN95.N-A:ASP33.O 48.21%
A:VAL114.N-A:TYR126.O 49.20%
A:PHE8.N-A:SER113.OG 46.61%
A:LYS88.N-A:SER81.O 48.01%
A:TYR37.N-A:LEU30.O 48.80%
A:ASP153.N-A:CYS156.O 46.02%
A:LEU89.N-A:VAL36.O 47.81%
A:THR257.OG1-A:LEU253.O 48.80%
A:VAL20.N-A:LEU27.O 45.82%
A:GLN189.N-A:MET49.O 47.81%
A:ALA70.N-A:VAL73.O 48.41%
A:GLY149.N-A:TYR161.O 45.62%
A:THR175.OG1-A:ASP176.O 47.61%
A:ASN95.N-A:ASP33.O 48.21%
A:GLN189.N-A:MET49.O 45.62%
A:LEU75.N-A:VAL68.O 47.41%
A:LEU87.N-A:CYS38.O 47.61%
A:LEU167.N-A:VAL171.O 45.42%
A:ASN231.N-A:LEU227.O 47.01%
A:ASN203.ND2-A:ASP289.O 46.61%
A:ASN203.ND2-A:ASP289.O 45.22%
(continued)
116
2 3C-Like Protease (3CLpro)
Table 2.31 (continued) SARS-CoV-2 rep1
rep2
rep3
A:GLN83.N-A:VAL86.O 46.61%
A:HIS172.N-A:ILE136.O 46.02%
A:LEU75.N-A:VAL68.O 45.02%
A:LEU167.N-A:VAL171.O 45.82%
A:VAL157.N-A:LYS100.O 45.82%
A:TYR54.OH-A:ASP187.O 44.82%
A:GLY109.N-A:MET130.O 45.82%
A:VAL18.N-A:GLY29.O 45.62%
A:LYS90.N-A:GLY79.O 44.82%
A:VAL157.N-A:LYS100.O 44.62%
A:SER144.OG-A:LEU141.O 45.22%
A:HIS172.N-A:ILE136.O 44.42%
A:ARG105.NH2-A:PHE181.O 44.42%
A:GLN19.N-A:GLN69.O 45.22%
A:THR45.OG1-A:ASP48.OD2 44.22%
A:HIS172.N-A:ILE136.O 44.22%
A:PHE150.N-A:SER113.O 45.02%
A:LEU115.N-A:VAL148.O 43.82%
A:SER144.OG-A:LEU141.O 44.22%
A:LYS5.NZ-A:GLU290.OE1 44.82%
A:VAL157.N-A:LYS100.O 43.63%
A:ARG40.NE-A:ASP187.OD1 44.02%
A:GLN299.NE2-A:ARG4.O 44.62%
A:ALA173.N-A:MET165.O 43.03%
A:VAL91.N-A:ASP34.O 43.43%
A:LEU75.N-A:VAL68.O 44.42%
A:ASN95.ND2-A:TRP31.O 42.83%
A:LYS90.N-A:GLY79.O 43.43%
A:LYS90.N-A:GLY79.O 44.22%
A:LYS5.NZ-A:GLU290.OE1 41.63%
A:TYR182.N-A:GLY174.O 43.03%
A:VAL91.N-A:ASP34.O 43.63%
A:ARG105.NH2-A:PHE181.O 41.43%
A:PHE112.N-A:CYS128.O 42.63%
A:TYR182.N-A:GLY174.O 43.23%
A:ALA70.N-A:VAL73.O 41.24%
A:CYS128.N-A:PHE112.O 42.43%
A:SER147.OG-A:SER144.O 43.23%
A:LEU205.N-A:THR201.O 41.24%
A:ARG40.NH2-A:ASP187.OD2 41.24%
A:PHE8.N-A:SER113.OG 42.83%
A:GLN192.NE2-A:VAL186.O 41.24%
A:ASN203.ND2-A:ASP289.O 41.24%
A:PHE112.N-A:CYS128.O 42.23%
A:VAL91.N-A:ASP34.O 40.64%
A:LEU30.N-A:TYR37.O 40.44%
A:TYR118.N-A:SER121.O 42.03%
A:GLN83.N-A:VAL86.O 40.44%
A:THR199.N-A:ASN238.O 39.84%
A:ASN95.ND2-A:TRP31.O 41.63%
A:THR175.OG1-A:ASP176.O 40.44%
A:PHE8.N-A:SER113.OG 39.64%
A:ILE281.N-A:SER284.O 41.43%
A:PHE150.N-A:SER113.O 40.24%
A:ASN95.ND2-A:TRP31.O 42.83%
A:ASN231.N-A:LEU227.O 41.24%
A:PHE112.N-A:CYS128.O 39.44%
A:ALA173.N-A:MET165.O 38.84%
A:LEU205.N-A:THR201.O 41.04%
A:SER123.N-A:ALA116.O 39.04%
A:ILE281.N-A:SER284.O 38.65%
A:LEU242.N-A:ASN231.OD1 40.24%
A:LYS88.N-A:SER81.O 38.84%
A:VAL18.N-A:GLY29.O 38.65%
A:GLN83.N-A:VAL86.O 39.64%
A:ASN133.ND2-A:GLY195.O 38.84%
A:CYS22.N-A:THR25.O 37.45%
A:ASN133.ND2-A:GLY195.O 39.64%
A:LEU32.N-A:VAL35.O 38.05%
A:TYR239.N-A:ALA234.O 37.45%
A:THR45.OG1-A:ASP48.OD1 39.64%
A:ILE281.N-A:SER284.O 37.85%
A:THR25.OG1-A:CYS44.O 37.25%
A:GLN189.N-A:MET49.O 39.04%
A:VAL18.N-A:GLY29.O 37.45%
A:ASN203.ND2-A:GLY109.O 37.25%
A:GLU14.N-A:SER10.O 38.45%
A:SER254.OG-A:ILE259.O 36.85%
A:GLU14.N-A:SER10.O 36.85%
A:ARG105.NH2-A:PHE181.O 37.85%
A:THR199.N-A:ASN238.O 36.85%
A:LEU205.N-A:THR201.O 36.85%
A:TYR239.N-A:ALA234.O 37.85%
A:LEU30.N-A:TYR37.O 36.45%
A:PHE150.N-A:SER113.O 36.45%
A:GLN192.NE2-A:VAL186.O 36.85%
A:LEU242.N-A:ASN231.OD1 36.45%
A:LEU32.N-A:VAL35.O 36.25%
A:ARG40.NE-A:ASP187.OD2 36.65%
A:CYS22.N-A:THR25.O 35.86%
A:TYR118.N-A:SER121.O 35.06%
A:LEU30.N-A:TYR37.O 36.45%
A:TYR118.N-A:SER121.O 35.06%
A:TRP218.NE1-A:THR280.O 34.86%
A:THR175.OG1-A:ASP176.O 35.86%
A:THR25.OG1-A:CYS44.O 34.86%
A:SER158.N-A:ASN151.O 34.66%
A:ARG131.N-A:THR135.O 35.66%
A:GLU14.N-A:SER10.O 34.86%
A:SER254.OG-A:ILE259.O 34.46%
A:CYS22.N-A:THR25.O 35.46%
A:CYS128.N-A:PHE112.O 34.66%
A:THR135.OG1-A:ASN133.OD1 34.06%
A:SER158.N-A:ASN151.O 35.26%
A:ASN203.ND2-A:GLY109.O 34.26%
A:THR45.OG1-A:ASP48.OD1 34.06%
A:LEU32.N-A:VAL35.O 35.06%
A:SER158.N-A:ASN151.O 33.67%
A:SER113.N-A:PHE150.O 32.27%
A:ASP153.N-A:CYS156.O 34.06%
A:TYR239.N-A:ALA234.O 33.07%
A:HIS41.NE2-A:HIS164.O 32.27%
A:SER113.N-A:PHE150.O 33.86%
A:LYS269.N-A:CYS265.O 32.67%
Table 2.32 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-2-Mpro-6y2e model (denoted as “SARS-CoV-2 dimer”) —the model has three sets of MD simulations [346] (continuation-1) A:VAL86.N-A:GLN83.O 31.87%
A:THR199.N-A:ASN238.O 33.67%
A:ASN28.ND2-A:CYS145.O 32.47%
A:ALA210.N-A:ALA206.O 30.88%
A:ILE200.N-A:ASP289.OD2 33.47%
A:THR21.N-A:LEU67.O 32.27%
A:ASN151.ND2-A:THR111.O 30.88%
A:SER254.OG-A:ILE259.O 32.87%
A:LEU268.N-A:MET264.O 32.07%
A:LEU268.N-A:MET264.O 30.48%
A:TYR54.OH-A:ASP187.O 32.87%
A:ASN231.N-A:LEU227.O 31.27%
A:THR45.OG1-A:ASP48.OD2 30.28%
A:ARG40.NH2-A:ASP187.OD1 32.27%
A:CYS160.N-A:GLY149.O 30.28%
A:ASN84.ND2-A:GLU178.O 30.28%
A:ALA116.N-A:GLY124.O 31.08%
A:ARG131.N-A:THR135.O 29.68%
A:GLN107.N-A:GLN110.OE1 29.88%
A:LEU268.N-A:MET264.O 31.08%
A:ARG4.NH1-B:GLU290.OE2 29.08%
A:CYS160.N-A:GLY149.O 29.48%
A:ALA173.N-A:MET165.O 30.68%
A:MET130.N-A:GLN110.O 28.88%
A:LYS269.N-A:CYS265.O 29.28%
A:CYS128.N-A:PHE112.O 30.68%
A:THR111.OG1-A:ASP295.OD2 28.88%
A:THR243.OG1-A:HIS246.ND1 29.28%
A:THR111.OG1-A:ASP295.OD2 30.68%
A:ASN95.ND2-A:GLY15.O 28.49%
A:THR21.N-A:LEU67.O 29.08%
A:ASN151.ND2-A:THR111.O 30.68%
A:ASN214.ND2-A:ALA210.O 28.29%
A:GLY120.N-A:ASN28.OD1 28.88%
A:ASN214.ND2-A:ALA210.O 30.28%
A:ALA255.N-A:GLY251.O 28.29%
A:ALA116.N-A:GLY124.O 28.88%
A:ASN203.ND2-A:GLY109.O 29.68%
A:SER81.N-A:LYS88.O 27.09%
(continued)
2.4 Concluding Remarks
117
Table 2.32 (continued) A:HIS80.ND1-A:ASN63.OD1 27.89%
A:THR21.N-A:LEU67.O 29.68%
A:LEU208.N-A:VAL204.O 27.09%
A:GLN192.NE2-A:VAL186.O 27.89%
A:ASN95.ND2-A:GLY15.O 29.28%
A:ALA234.N-A:PHE230.O 26.69%
A:TYR126.N-A:VAL114.O 27.09%
A:GLY11.N-B:GLU14.OE2 29.08%
A:CYS38.N-A:LEU87.O 26.69%
A:ASN221.N-A:SER267.OG 26.89%
A:LYS269.N-A:CYS265.O 29.08%
A:THR21.OG1-A:THR26.OG1 25.70%
A:ASN95.ND2-A:GLY15.O 26.10%
A:THR243.OG1-A:HIS246.ND1 28.49%
A:SER113.N-A:PHE150.O 25.70%
A:ILE136.N-A:HIS172.O 25.50%
A:VAL86.N-A:GLN83.O 28.09%
A:GLY302.N-A:VAL297.O 25.70%
A:ALA255.N-A:GLY251.O 25.30%
A:LEU208.N-A:VAL204.O 27.89%
A:TRP218.NE1-A:THR280.O 24.90%
A:THR198.OG1-A:GLU240.OE2 25.10%
A:ILE136.N-A:HIS172.O 27.89%
A:VAL186.N-A:GLN192.OE1 24.70%
A:SER81.N-A:LYS88.O 24.90%
A:GLY120.N-A:ASN28.OD1 27.09%
A:ILE200.N-A:ASP289.OD2 24.50%
A:LEU67.N-A:THR21.O 24.70%
A:LEU67.N-A:THR21.O 27.09%
A:LEU67.N-A:THR21.O 24.50%
A:THR21.OG1-A:THR26.OG1 24.50%
A:VAL104.N-A:PHE159.O 26.29%
A:THR243.OG1-A:HIS246.ND1 24.50%
A:ASN231.ND2-A:LEU242.O 24.30%
A:THR21.OG1-A:THR26.OG1 26.10%
A:GLN273.N-A:LYS269.O 23.71%
A:ARG105.NH1-A:ASP176.OD2 23.90%
A:ASN221.N-A:SER267.OG 26.10%
A:ASN221.N-A:SER267.OG 23.31%
A:VAL104.N-A:PHE159.O 23.90%
A:SER81.N-A:LYS88.O 26.10%
A:ASP92.N-A:ARG76.O 23.11%
A:ASP216.N-A:ALA211.O 23.90%
A:ALA255.N-A:GLY251.O 25.70%
A:ALA210.N-A:ALA206.O 22.71%
A:SER62.N-A:ASN65.OD1 23.31%
A:TRP218.NE1-A:THR280.O 25.30%
A:LYS102.N-A:VAL157.O 22.31%
A:ASN180.N-A:ASP176.OD1 23.31%
A:LYS102.N-A:VAL157.O 25.30%
A:ASN151.N-A:SER158.O 22.31%
A:THR198.OG1-A:GLU240.OE1 22.71%
A:GLN107.N-A:GLN110.OE1 25.10%
A:VAL86.N-A:GLN83.O 22.31%
A:LYS102.N-A:VAL157.O 22.51%
A:ARG4.N-A:GLN299.OE1 25.10%
A:ASN180.N-A:ASP176.OD1 22.11%
A:CYS38.N-A:LEU87.O 22.51%
A:ASN231.ND2-A:LEU242.O 24.90%
A:THR45.N-A:ASP48.OD2 21.71%
A:THR111.OG1-A:GLU290.O 22.51%
A:ASN28.ND2-A:CYS145.O 24.70%
A:VAL104.N-A:PHE159.O 21.71%
A:LYS97.N-A:ASN95.OD1 22.31%
A:ALA234.N-A:PHE230.O 24.50%
A:ASN65.N-A:SER62.O 21.51%
A:THR225.OG1-A:PHE223.O 22.31%
A:CYS160.N-A:GLY149.O 24.30%
A:ASN238.ND2-A:ASP197.O 21.51%
A:CYS156.N-A:ASP153.O 22.11%
A:ARG131.NH2-A:ASP289.OD2 24.10%
A:THR45.OG1-A:ASP48.OD1 21.31%
A:ASN151.N-A:SER158.O 21.91%
A:THR292.OG1-A:ASP295.OD2 24.10%
A:ASN151.ND2-A:THR111.O 21.12%
A:VAL186.N-A:GLN192.OE1 21.71%
A:THR45.OG1-A:ASP48.OD2 23.71%
A:THR98.OG1-A:ASP33.OD2 21.12%
A:THR226.OG1-A:ASP229.OD1 21.71%
A:GLY302.N-A:VAL297.O 22.91%
A:LYS5.NZ-A:GLU288.OE2 20.92%
A:ASN119.ND2-A:GLN19.OE1 21.51%
A:THR198.OG1-A:GLU240.OE1 22.71%
A:ALA116.N-A:GLY124.O 20.92%
A:CYS300.N-A:VAL296.O 21.31%
A:GLN69.N-A:GLN19.O 22.51%
A:THR98.OG1-A:ASP33.OD1 20.32%
A:THR226.OG1-A:ASP229.OD2 21.31%
A:THR111.OG1-A:ASP295.OD1 22.51%
A:GLY120.N-A:ASN28.OD1 20.12%
A:PHE134.N-A:ARG131.O 21.31%
A:LYS5.NZ-A:GLU288.OE1 22.11%
A:HIS41.NE2-A:HIS164.O 20.12%
A:LYS100.NZ-A:ASP155.OD1 20.92%
A:ARG40.NH2-A:ASP187.OD2 22.11%
A:ARG105.NH1-A:ASP176.OD2 20.12%
A:PHE159.N-A:LYS102.O 20.72%
A:THR25.OG1-A:CYS44.O 21.91%
A:CYS156.N-A:ASP153.O 20.12%
A:ALA7.N-B:VAL125.O 20.52%
A:ASN151.N-A:SER158.O 21.91%
A:ASN180.N-A:ASP176.OD2 20.12%
A:THR198.OG1-A:GLU240.OE2 21.71%
B:SER10.OG-B:GLU14.OE2 83.27%
A:VAL186.N-A:GLN192.OE1 21.31%
B:TYR209.OH-B:ILE259.O 71.91%
B:SER267.OG-B:ASP263.O 67.13%
A:ALA210.N-A:ALA206.O 20.92%
B:SER267.OG-B:ASP263.O 71.51%
B:TYR209.OH-B:ILE259.O 66.93%
A:THR98.OG1-A:ASN95.O 20.92%
B:ILE78.N-B:LYS90.O 64.94%
B:TYR182.OH-B:CYS160.O 65.14%
A:HIS80.ND1-A:ASN63.OD1 20.72%
B:THR201.OG1-B:GLU240.O 60.36%
B:TRP31.N-B:CYS16.O 64.54%
A:CYS38.N-A:LEU87.O 20.72%
B:TRP31.N-B:CYS16.O 59.76%
B:SER10.OG-B:GLU14.OE2 63.94%
A:MET130.N-A:GLN110.O 20.72%
B:HIS163.N-B:SER147.O 59.76%
B:ILE78.N-B:LYS90.O 63.75%
A:SER62.N-A:ASN65.OD1 20.52%
B:TYR182.OH-B:CYS160.O 58.57%
B:THR201.OG1-B:GLU240.O 61.75%
A:SER301.OG-A:GLN256.OE1 20.52%
B:VAL20.N-B:LEU27.O 56.77%
B:SER147.OG-B:SER144.O 59.76%
A:PHE159.N-A:LYS102.O 20.12%
B:VAL36.N-B:LEU89.O 54.18%
B:ALA173.N-B:MET165.O 57.57%
A:TYR126.N-A:VAL114.O 20.12%
B:THR257.OG1-B:LEU253.O 53.39%
B:THR135.OG1-B:ASN133.OD1 55.98%
B:GLN19.N-B:GLN69.O 52.59%
B:LEU87.N-B:CYS38.O 55.18%
B:SER10.OG-B:GLU14.OE2 84.86%
B:VAL157.N-B:LYS100.O 51.59%
B:VAL114.N-B:TYR126.O 53.98%
B:TRP31.N-B:CYS16.O 70.52%
B:ASN95.N-B:ASP33.O 51.59%
B:THR257.OG1-B:LEU253.O 52.99%
B:SER267.OG-B:ASP263.O 68.33%
B:LYS88.N-B:SER81.O 51.00%
B:VAL36.N-B:LEU89.O 51.99%
B:HIS163.N-B:SER147.O 62.15%
B:LEU27.N-B:VAL20.O 51.00%
B:TYR182.N-B:GLY174.O 51.79%
B:TYR209.OH-B:ILE259.O 61.35%
B:SER147.OG-B:SER144.O 50.80%
B:TYR37.N-B:LEU30.O 51.79%
B:ILE78.N-B:LYS90.O 60.36%
B:GLY149.N-B:TYR161.O 50.40%
B:HIS163.N-B:SER147.O 51.20%
B:THR201.OG1-B:GLU240.O 60.16%
B:TYR37.N-B:LEU30.O 50.20%
B:TYR54.OH-B:ASP187.O 51.00%
B:VAL114.N-B:TYR126.O 58.76%
B:TYR118.N-B:SER121.O 50.00%
B:GLN19.N-B:GLN69.O 51.00%
B:TYR182.OH-B:CYS160.O 57.57%
B:ASP153.N-B:CYS156.O 49.60%
B:LEU27.N-B:VAL20.O 50.00%
B:LEU27.N-B:VAL20.O 54.78%
B:LEU87.N-B:CYS38.O 49.00%
B:ALA70.N-B:VAL73.O 49.60%
B:GLY109.N-B:MET130.O 54.38%
B:VAL114.N-B:TYR126.O 48.80%
B:LYS88.N-B:SER81.O 49.00%
B:GLY146.N-B:HIS163.O 53.39%
B:THR135.OG1-B:ASN133.OD1 47.81%
B:ARG105.NH2-B:PHE181.O 47.81%
B:TYR37.N-B:LEU30.O 52.19%
B:PHE8.N-B:SER113.OG 47.01%
B:VAL157.N-B:LYS100.O 47.81%
B:THR257.OG1-B:LEU253.O 51.99%
B:CYS22.N-B:THR25.O 45.82%
B:LEU89.N-B:VAL36.O 47.41%
B:VAL36.N-B:LEU89.O 51.59%
B:PHE150.N-B:SER113.O 45.62%
B:THR175.OG1-B:ASP176.O 45.82%
B:PHE112.N-B:CYS128.O 51.39%
B:LEU89.N-B:VAL36.O 45.02%
B:ASN95.N-B:ASP33.O 45.42%
B:LEU89.N-B:VAL36.O 50.40%
B:ASN203.ND2-B:ASP289.O 44.82%
B:GLN299.NE2-B:ARG4.O 45.22%
B:VAL20.N-B:LEU27.O 50.20%
B:PHE112.N-B:CYS128.O 44.82%
B:PHE150.N-B:SER113.O 45.02%
B:VAL157.N-B:LYS100.O 50.00%
B:LYS90.N-B:GLY79.O 44.42%
B:LEU30.N-B:TYR37.O 43.82%
B:GLN19.N-B:GLN69.O 49.80%
B:ALA70.N-B:VAL73.O 43.82%
B:GLY146.N-B:HIS163.O 43.82%
B:SER147.OG-B:SER144.O 49.00%
B:GLN299.NE2-B:ASP295.O 43.82%
118
2 3C-Like Protease (3CLpro)
Table 2.33 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-2-Mpro-6y2e model (denoted as “SARS-CoV-2 dimer”) —the model has three sets of MD simulations [346] (continuation-2) B:ASN133.ND2-B:GLY195.O 43.63%
B:LEU242.N-B:ASN231.OD1 47.81%
B:ALA173.N-B:MET165.O 43.43%
B:ASN203.ND2-B:ASP289.O 43.63%
B:LYS88.N-B:SER81.O 47.81%
B:GLN192.NE2-B:VAL186.O 43.23%
B:GLN189.N-B:MET49.O 43.03%
B:ASP153.N-B:CYS156.O 47.41%
B:TYR239.N-B:ALA234.O 42.63%
B:PHE8.N-B:SER113.OG 43.03%
B:ASN203.ND2-B:GLY109.O 46.81%
B:THR199.N-B:ASN238.O 42.23%
B:GLN83.N-B:VAL86.O 42.63%
B:ASN95.N-B:ASP33.O 46.22%
B:ASN133.ND2-B:GLY195.O 42.23%
B:GLY109.N-B:MET130.O 42.63%
B:LEU75.N-B:VAL68.O 46.02%
B:LEU75.N-B:VAL68.O 42.03%
B:LEU167.N-B:VAL171.O 42.43%
B:VAL18.N-B:GLY29.O 45.82%
B:SER123.N-B:ALA116.O 42.03%
B:GLY149.N-B:TYR161.O 42.43%
B:LEU167.N-B:VAL171.O 45.82%
B:THR175.OG1-B:ASP176.O 41.63%
B:HIS172.N-B:ILE136.O 42.03%
B:PHE8.N-B:SER113.OG 45.82%
B:LEU167.N-B:VAL171.O 40.84%
B:VAL91.N-B:ASP34.O 42.03%
B:LEU87.N-B:CYS38.O 45.62%
B:GLN83.N-B:VAL86.O 40.44%
B:LYS90.N-B:GLY79.O 41.43%
B:ARG105.NH2-B:PHE181.O 45.62%
B:VAL91.N-B:ASP34.O 40.44%
B:LEU242.N-B:ASN231.OD1 41.43%
B:SER144.OG-B:LEU141.O 45.42%
B:TYR182.N-B:GLY174.O 40.04%
B:VAL18.N-B:GLY29.O 40.84%
B:THR135.OG1-B:ASN133.OD1 44.82%
B:THR292.OG1-B:ASP295.OD1 39.64%
B:VAL20.N-B:LEU27.O 40.84%
B:ASN203.ND2-B:ASP289.O 44.82%
B:THR21.N-B:LEU67.O 39.64%
B:ILE281.N-B:SER284.O 40.44%
B:ALA70.N-B:VAL73.O 44.42%
B:LEU205.N-B:THR201.O 39.44%
B:ASN231.N-B:LEU227.O 40.44%
B:THR175.OG1-B:ASP176.O 43.63%
B:GLY109.N-B:MET130.O 38.84%
B:THR199.N-B:ASN238.O 40.24%
B:SER123.N-B:ALA116.O 43.43%
B:ARG40.NH2-B:ASP187.OD2 38.25%
B:LEU75.N-B:VAL68.O 39.84%
B:LYS90.N-B:GLY79.O 43.03%
B:THR45.OG1-B:ASP48.OD2 38.25%
B:ASN28.ND2-B:CYS145.O 39.64%
B:GLN299.NE2-B:ARG4.O 41.63%
B:ARG131.N-B:THR135.O 37.65%
B:THR45.OG1-B:ASP48.OD1 39.64%
B:LEU115.N-B:VAL148.O 41.43%
B:ARG40.NE-B:ASP187.OD1 37.45%
B:TYR239.N-B:ALA234.O 39.44%
B:TYR182.N-B:GLY174.O 41.24%
B:ASN84.ND2-B:GLU178.O 37.05%
B:SER158.N-B:ASN151.O 37.65%
B:ASN231.N-B:LEU227.O 41.04%
B:LEU32.N-B:VAL35.O 37.05%
B:LEU205.N-B:THR201.O 37.45%
B:THR111.OG1-B:GLU290.O 40.04%
B:GLU14.N-B:SER10.O 36.45%
B:THR111.OG1-B:ASP295.OD2 37.05%
B:GLN83.N-B:VAL86.O 39.44%
B:THR25.OG1-B:CYS44.O 36.25%
B:SER113.N-B:PHE150.O 36.85%
B:ALA173.N-B:MET165.O 39.44%
B:ASN95.ND2-B:TRP31.O 35.86%
B:LEU32.N-B:VAL35.O 36.65%
B:LEU30.N-B:TYR37.O 39.24%
B:SER158.N-B:ASN151.O 35.46%
B:ASN95.ND2-B:TRP31.O 36.45%
B:ASN95.ND2-B:TRP31.O 39.04%
B:GLY146.N-B:HIS163.O 35.06%
B:TYR118.N-B:SER121.O 36.06%
B:TYR54.OH-B:ASP187.O 38.84%
B:SER113.OG-B:GLN127.OE1 34.66%
B:ASN151.ND2-B:THR111.O 35.66%
B:THR45.OG1-B:ASP48.OD1 38.65%
B:ARG298.NH2-B:ASP295.OD2 34.46%
B:GLN192.NE2-B:VAL186.O 35.66%
B:TYR239.N-B:ALA234.O 38.25%
B:LYS269.N-B:CYS265.O 34.06%
B:SER254.OG-B:ILE259.O 35.06%
B:ILE281.N-B:SER284.O 38.05%
B:LEU242.N-B:ASN231.OD1 33.86%
B:SER123.N-B:ALA116.O 34.86%
B:THR199.N-B:ASN238.O 38.05%
B:LEU115.N-B:VAL148.O 33.47%
B:ARG40.NE-B:ASP187.OD2 34.26%
B:GLN189.N-B:MET49.O 37.85%
B:ASN231.N-B:LEU227.O 32.67%
B:ARG40.NH2-B:ASP187.OD1 34.26%
B:LEU205.N-B:THR201.O 37.65%
B:CYS128.N-B:PHE112.O 32.07%
B:GLU14.N-B:SER10.O 34.06%
B:PHE150.N-B:SER113.O 37.45%
B:ARG298.N-B:PHE294.O 32.07%
B:LEU115.N-B:VAL148.O 32.87%
B:ASN133.ND2-B:GLY195.O 36.85%
B:LEU30.N-B:TYR37.O 31.47%
B:GLN107.N-B:GLN110.OE1 32.07%
B:HIS172.N-B:ILE136.O 36.65%
B:ARG105.NH2-B:PHE181.O 31.47%
B:THR111.OG1-B:ASP295.OD1 31.87%
B:VAL91.N-B:ASP34.O 36.25%
B:VAL86.N-B:GLN83.O 31.47%
B:ILE200.N-B:ASP289.OD1 31.87%
B:LEU32.N-B:VAL35.O 35.86%
B:ARG4.N-B:GLN299.OE1 31.47%
B:THR292.OG1-B:ASP295.OD2 31.47%
B:CYS22.N-B:THR25.O 35.86%
B:SER144.OG-B:CYS117.O 30.68%
B:MET130.N-B:GLN110.O 30.88%
B:GLY149.N-B:TYR161.O 35.66%
B:VAL18.N-B:GLY29.O 30.48%
B:ALA255.N-B:GLY251.O 30.68%
B:SER254.OG-B:ILE259.O 35.26%
B:ALA116.N-B:GLY124.O 30.08%
B:THR21.N-B:LEU67.O 30.48%
B:ARG298.NH2-B:MET6.O 34.06%
B:LEU268.N-B:MET264.O 30.08%
B:THR292.OG1-B:ASP295.OD1 30.28%
B:THR21.N-B:LEU67.O 33.07%
B:ASN95.ND2-B:GLY15.O 29.68%
B:LEU268.N-B:MET264.O 29.68%
B:CYS128.N-B:PHE112.O 32.07%
B:GLN69.N-B:GLN19.O 29.48%
B:LEU67.N-B:THR21.O 29.48%
B:TYR118.N-B:SER121.O 32.07%
B:ILE281.N-B:SER284.O 28.88%
B:PHE112.N-B:CYS128.O 28.88%
B:SER113.N-B:PHE150.O 31.47%
B:LYS102.N-B:VAL157.O 28.29%
B:VAL86.N-B:GLN83.O 28.29%
B:LEU268.N-B:MET264.O 31.08%
B:MET130.N-B:GLN110.O 27.69%
B:LYS269.N-B:CYS265.O 28.09%
B:GLU14.N-B:SER10.O 30.88%
B:GLN107.N-B:GLN110.OE1 26.89%
B:LEU208.N-B:VAL204.O 27.49%
B:ALA255.N-B:GLY251.O 30.88%
B:THR45.OG1-B:ASP48.OD1 26.49%
B:ASN151.N-B:SER158.O 27.29%
B:THR25.OG1-B:CYS44.O 30.88%
B:SER81.N-B:LYS88.O 26.10%
B:CYS22.N-B:THR25.O 27.09%
B:ARG40.NH2-B:ASP187.OD1 30.48%
B:LYS5.NZ-B:GLU290.OE1 25.90%
B:ARG4.N-B:GLN299.OE1 26.69%
B:THR45.OG1-B:ASP48.OD2 29.88%
B:TYR126.N-B:VAL114.O 25.90%
B:THR45.OG1-B:ASP48.OD2 26.29%
B:LYS269.N-B:CYS265.O 29.48%
B:CYS160.N-B:GLY149.O 25.30%
B:CYS38.N-B:LEU87.O 25.90%
B:ARG40.NE-B:ASP187.OD2 28.88%
B:LEU67.N-B:THR21.O 25.30%
B:SER121.OG-B:TYR118.O 25.50%
B:SER158.N-B:ASN151.O 28.49%
B:LYS5.NZ-B:GLU288.OE1 25.10%
(continued)
2.4 Concluding Remarks
119
Table 2.33 (continued) B:SER62.N-B:ASN65.OD1 25.50%
B:LYS102.N-B:VAL157.O 28.49%
B:TRP218.NE1-B:THR280.O 24.90%
B:HIS80.ND1-B:ASN63.OD1 25.30%
B:THR243.OG1-B:HIS246.ND1 28.29%
B:HIS172.N-B:ILE136.O 24.90%
B:ASP153.N-B:CYS156.O 24.90%
B:ASN231.ND2-B:LEU242.O 28.09%
B:THR198.OG1-B:GLU240.OE1 24.90%
B:LYS5.NZ-B:GLU290.OE2 24.90%
B:ARG131.N-B:THR135.O 28.09%
B:GLY302.N-B:VAL297.O 24.90%
B:ASN221.N-B:SER267.OG 24.70%
B:GLN192.NE2-B:VAL186.O 28.09%
B:VAL104.N-B:PHE159.O 24.50%
B:THR25.OG1-B:CYS44.O 24.70%
B:LEU208.N-B:VAL204.O 27.69%
B:ALA255.N-B:GLY251.O 24.50%
B:ASN231.ND2-B:LEU242.O 24.50%
B:ARG4.N-B:GLN299.OE1 27.29%
B:ASN180.N-B:ASP176.OD2 24.30%
B:TRP218.NE1-B:THR280.O 24.30%
B:TRP218.NE1-B:THR280.O 26.89%
B:GLN299.NE2-B:ARG4.O 23.90%
B:CYS128.N-B:PHE112.O 24.10%
B:GLN107.N-B:GLN110.OE1 26.69%
B:VAL186.N-B:GLN192.OE1 23.71%
B:ASN180.N-B:ASP176.OD2 24.10%
B:ASN214.ND2-B:ALA210.O 26.49%
B:LEU272.N-B:LEU268.O 23.71%
B:ASN84.ND2-B:GLU178.O 23.71%
B:ALA116.N-B:GLY124.O 26.49%
B:LYS5.NZ-B:GLU290.OE2 23.71%
B:CYS300.N-B:VAL296.O 23.51%
B:SER81.N-B:LYS88.O 26.10%
B:TYR54.OH-B:ASP187.O 23.31%
B:LYS102.N-B:VAL157.O 23.31%
B:ASN221.N-B:SER267.OG 25.90%
B:LEU208.N-B:VAL204.O 23.11%
B:ARG131.N-B:THR135.O 23.31%
B:THR198.OG1-B:GLU240.OE2 25.70%
B:GLN189.N-B:MET49.O 23.11%
B:SER81.N-B:LYS88.O 23.11%
B:ASN28.ND2-B:CYS145.O 25.70%
B:SER139.N-B:TYR126.OH 23.11%
B:PHE159.N-B:LYS102.O 23.11%
B:THR21.OG1-B:THR26.OG1 25.10%
B:SER62.N-B:ASN65.OD1 22.91%
B:ASN203.ND2-B:GLY109.O 22.91%
B:ASN180.N-B:ASP176.OD1 24.50%
B:SER284.N-B:ILE281.O 22.91%
B:ARG105.NH1-B:ASP176.OD1 22.71%
B:LEU67.N-B:THR21.O 24.50%
B:ASN221.N-B:SER267.OG 22.91%
B:THR93.OG1-B:ASP92.OD2 22.51%
B:VAL86.N-B:GLN83.O 24.50%
B:HIS164.N-B:ALA173.O 22.71%
B:CYS160.N-B:GLY149.O 22.31%
B:ASN151.N-B:SER158.O 24.50%
B:SER254.OG-B:ILE259.O 22.31%
B:LYS5.NZ-B:GLU290.OE1 22.11%
B:VAL104.N-B:PHE159.O 24.30%
B:ASN231.ND2-B:LEU242.O 21.91%
B:ASN95.ND2-B:GLY15.O 21.91%
B:HIS80.ND1-B:ASN63.OD1 23.71%
B:THR21.OG1-B:THR26.OG1 21.51%
B:ALA116.N-B:GLY124.O 21.51%
B:LYS5.NZ-B:GLU290.OE2 23.51%
B:CYS156.N-B:ASP153.O 21.31%
B:HIS41.NE2-B:HIS164.O 21.51%
B:CYS265.N-B:VAL261.O 23.11%
B:SER113.N-B:PHE150.O 21.12%
B:ARG131.NH2-B:ASP289.OD1 21.51%
B:ILE200.N-B:ASP289.OD1 22.71%
B:ASP92.N-B:ARG76.O 20.92%
B:THR243.OG1-B:HIS246.ND1 21.31%
B:ARG105.NH1-B:ASP176.OD2 22.71%
B:CYS265.N-B:VAL261.O 20.52%
B:THR198.OG1-B:GLU240.OE2 21.12%
B:ASN95.ND2-B:GLY15.O 22.31%
B:THR26.OG1-B:THR21.OG1 20.52%
B:GLY120.N-B:ASN28.OD1 21.12%
B:CYS300.N-B:VAL296.O 21.91%
B:ASN180.N-B:ASP176.OD1 20.32%
B:VAL186.N-B:GLN192.OE1 20.92%
B:SER62.N-B:ASN65.OD1 21.51%
B:ASN203.ND2-B:GLY109.O 20.12%
B:THR292.N-B:ASP295.OD2 20.92%
B:ASN151.ND2-B:THR111.O 21.51%
B:CYS265.N-B:VAL261.O 20.72%
B:SER139.N-B:TYR126.OH 21.12%
B:THR21.OG1-B:THR26.OG1 20.12%
B:LYS5.NZ-B:GLU290.OE1 20.72% B:SER121.N-B:TYR118.O 20.72% B:CYS38.N-B:LEU87.O 20.52%
120
2 3C-Like Protease (3CLpro)
Table 2.34 The MD-SBs of monomeric the SARS-CoV-1-Mpro-N3-2hob model (denoted as “SARS-CoV-1-N3 monomer”) and the SARS-CoV-2-Mpro-N3-6lu7 model (denoted as “SARSCoV-2-N3 monomer”), where each model has three sets of MD simulations [346] SARS-CoV-1-N3 rep1
rep2
rep3
SARS-CoV-2-N3 rep1
ASP153-ARG298
rep2
rep3
ASP153-ARG298
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12 ASP155-LYS102
ASP155-LYS102
ASP155-LYS102
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP176-LYS180
ASP176-LYS180
ASP187-ARG188
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12 ASP176-ARG105
ASP176-LYS180 ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP187-ARG40 ASP187-HIS41
ASP187-HIS41
ASP216-ARG217 ASP229-LYS269
ASP229-LYS269
ASP229-LYS269
ASP229-LYS269
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP229-LYS269
ASP245-HIS246 ASP263-ARG222
ASP263-ARG222
ASP263-ARG222
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP289-LYS137
ASP289-LYS137
ASP289-LYS137
ASP289-LYS137
ASP263-ARG222
ASP289-LYS137
ASP263-ARG222
ASP289-LYS137
ASP263-ARG222
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP295-LYS5 ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP48-ARG60
ASP48-ARG60
ASP48-ARG60
ASP48-ARG60
ASP48-ARG60
ASP48-ARG60
ASP48-LYS61
ASP48-LYS61
ASP56-ARG60
ASP56-ARG60
ASP56-ARG60
ASP56-ARG60
ASP56-ARG60
ASP56-ARG60
ASP92-ARG76
ASP92-ARG76
ASP92-ARG76
ASP92-ARG76
ASP92-ARG76
ASP92-ARG76
GLU14-LYS97
GLU14-LYS97
GLU166-HIS172
GLU166-HIS172
GLU166-HIS172
GLU166-HIS172
GLU166-HIS172
GLU166-HIS172
GLU178-LYS180
GLU178-LYS180 GLU240-HIS246
GLU14-LYS97 GLU178-ARG88
GLU178-ARG88 GLU178-ARG105
GLU178-ARG105 GLU178-LYS180 GLU240-HIS246
GLU240-HIS246
GLU270-ARG222
GLU270-ARG222
GLU270-LYS269
GLU270-LYS269
GLU270-LYS269
GLU178-LYS88 GLU178-ARG105
GLU178-ARG105
GLU178-ARG105
GLU240-HIS246
GLU240-HIS246
GLU240-HIS246
GLU270-ARG222
GLU270-ARG222
GLU270-ARG222
GLU270-LYS269
GLU270-LYS269
GLU270-LYS269
GLU288-LYS5
GLU288-LYS5
GLU270-ARG279 GLU288-ARG4
GLU288-ARG4
GLU288-LYS5
GLU288-ARG4 GLU288-LYS5
GLU288-LYS5
GLU288-LYS5
GLU288-LYS137
GLU288-LYS137
GLU288-LYS137
GLU288-LYS137
GLU290-ARG4
GLU290-ARG4
GLU288-ARG4
GLU288-ARG131 GLU290-ARG4 GLU290-LYS5
GLU290-LYS5
GLU290-LYS5
GLU290-LYS5
GLU288-LYS137 GLU290-LYS5
GLU290-ARG131
GLU290-ARG131
GLU290-ARG131
GLU290-ARG131
GLU290-ARG131
GLU290-LYS137
GLU290-LYS137
GLU290-LYS137
GLU290-LYS137
GLU290-LYS137
GLU47-ARG60
GLU47-ARG60
GLU47-ARG60
GLU55-ARG40
GLU55-ARG40
GLU55-ARG40
GLU55-ARG40
GLU55-ARG40
GLU55-ARG188
GLU288-LYS137 GLU290-ARG4 GLU290-LYS5 GLU290-LYS137 GLU55-ARG40
2.4 Concluding Remarks
121
Table 2.35 The MD-SBs of dimer the SARS-CoV-1-Mpro-N3-2hob model (denoted as “SARSCoV-1-N3 dimer”) and the SARS-CoV-2-Mpro-N3-6lu7 model (denoted as “SARS-CoV-2-N3 dimer”), where each model has three sets of MD simulations [346] SARS-CoV-1-N3 rep1
rep2
A:GLU14-B:LYS12
B:GLU14-A:LYS12
A:GLU14-B:LYS12
A:GLU290-B:ARG4
A:GLU290-B:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
B:GLU290-A:ARG4
B:GLU290-A:ARG4
rep3
A:ASP153-A:ARG298 A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS100
B:ASP155-B:LYS100
B:ASP155-B:LYS102
A:ASP155-A:LYS102
B:ASP155-B:LYS102
B:ASP155-B:LYS12
A:ASP155-A:LYS12
B:ASP155-B:LYS12
A:ASP155-A:LYS12
B:ASP155-B:LYS12
A:ASP155-A:LYS102 A:ASP155-A:LYS12 A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP176-A:LYS180
B:ASP176-B:LYS180
A:ASP176-A:LYS180
B:ASP176-B:LYS180
A:ASP176-A:LYS180
B:ASP176-B:LYS180
A:ASP187-A:ARG188
B:ASP187-B:ARG188
A:ASP187-A:ARG188
A:ASP187-A:ARG188
B:ASP187-B:ARG188
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP187-A:ARG40
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP197-A:LYS137
B:ASP197-B:LYS137
A:ASP197-A:LYS137
B:ASP197-B:LYS137
A:ASP197-A:ARG131
A:ASP216-A:ARG279
B:ASP216-B:ARG279
A:ASP197-A:LYS137
A:ASP216-A:ARG217
A:ASP187-A:HIS41
A:ASP216-A:ARG279
B:ASP216-B:ARG279
A:ASP229-A:LYS269
B:ASP229-B:LYS269
A:ASP216-A:ARG279
A:ASP229-A:LYS269
B:ASP229-B:LYS269
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP229-A:LYS269
B:ASP197-B:ARG131 B:ASP197-B:LYS137 B:ASP229-B:LYS269
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP289-A:LYS137
B:ASP289-B:LYS137
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP48-A:ARG60
B:ASP48-B:ARG60
A:ASP48-A:ARG60
B:ASP48-B:ARG60
A:ASP48-A:ARG60
B:ASP48-B:ARG60
A:ASP48-A:LYS61
B:ASP48-B:LYS61
A:ASP56-A:ARG60
B:ASP56-B:ARG60
A:ASP48-A:LYS61
B:ASP48-B:LYS61
A:ASP56-A:ARG60
B:ASP56-B:ARG60
A:ASP92-A:ARG76
B:ASP92-B:ARG76
A:ASP56-A:ARG60
B:ASP56-B:ARG60
A:ASP92-A:ARG76
B:ASP92-B:ARG76
A:GLU166-A:HIS172
B:GLU166-B:HIS172
A:ASP92-A:ARG76
B:ASP92-B:ARG76
A:GLU166-A:HIS172
B:GLU166-B:HIS172
A:GLU178-A:ARG88
B:GLU178-B:ARG88
A:GLU166-A:HIS172
B:GLU166-B:HIS172
A:GLU178-A:ARG105
B:GLU178-B:ARG105
A:GLU178-A:LYS180
B:GLU178-B:LYS180
A:GLU178-A:ARG88
A:GLU178-A:ARG88
B:GLU178-B:ARG88
A:GLU178-A:LYS180
B:GLU178-B:LYS180
A:GLU270-A:ARG222
B:GLU270-B:ARG222
A:GLU240-A:HIS246
B:GLU240-B:HIS246
A:GLU240-A:HIS246
B:GLU240-B:HIS246
A:GLU270-A:LYS269
B:GLU270-B:LYS269
A:GLU270-A:ARG222
B:GLU270-B:ARG222 B:GLU270-B:LYS269
A:GLU240-A:HIS246
B:GLU240-B:HIS246
A:GLU178-A:LYS180
A:GLU270-A:ARG222
B:GLU270-B:ARG222
A:GLU288-A:LYS5
B:GLU288-B:LYS5
A:GLU270-A:LYS269
A:GLU270-A:LYS269
B:GLU270-B:LYS269
A:GLU290-A:ARG131
B:GLU290-B:ARG131
A:GLU288-A:LYS137
A:GLU290-A:LYS137
B:GLU290-B:LYS137
A:GLU288-A:LYS5
B:GLU288-B:LYS5
A:GLU290-A:LYS5
B:GLU290-B:LYS5
A:GLU290-A:ARG131
A:GLU288-A:LYS137 A:GLU288-A:LYS5
B:GLU178-B:LYS180
B:GLU288-B:LYS5
A:GLU290-A:ARG131
B:GLU290-B:ARG131
A:GLU290-A:LYS137
B:GLU290-B:LYS137
A:GLU290-A:LYS137
B:GLU290-B:LYS137
A:GLU290-A:LYS5
B:GLU290-B:LYS5
A:GLU290-A:LYS5
B:GLU290-B:LYS5
A:GLU55-A:ARG40
B:GLU55-B:ARG40
A:GLU47-A:LYS61 A:GLU55-A:ARG40
B:ASP48-B:LYS61 B:GLU55-B:ARG40
B:GLU55-B:ARG40
B:ASP289-B:LYS137
B:GLU288-B:LYS137 B:GLU178-B:ARG105
B:GLU178-B:ARG105
B:ASP187-B:ARG40 B:GLU288-B:ARG131 SARS-CoV-2-N3 rep1
rep2
A:GLU288-B:ARG4
A:GLU14-B:LYS12
A:GLU14-B:LYS12
A:GLU290-B:ARG4
B:GLU14-A:LYS12
A:GLU290-B:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
B:GLU290-A:ARG4
rep3
B:GLU290-A:ARG4 A:ASP153-A:ARG298
A:ASP153-A:ARG298 A:ASP153-A:LYS102
B:ASP153-B:LYS102
A:ASP153-A:LYS102
A:ASP153-A:ARG298 B:ASP153-B:LYS102
A:ASP153-A:LYS102
B:ASP153-B:LYS102
(continued)
122
2 3C-Like Protease (3CLpro)
Table 2.35 (continued) SARS-CoV-1-N3 rep1
rep2
rep3
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS100
B:ASP155-B:LYS100
A:ASP155-A:LYS100
A:ASP155-A:LYS12
B:ASP155-B:LYS12
A:ASP155-A:LYS12
B:ASP155-B:LYS12
A:ASP155-A:LYS102
B:ASP155-B:LYS100
A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP155-A:LYS12
B:ASP155-B:LYS12
A:ASP187-A:ARG188
B:ASP187-B:ARG188
A:ASP187-A:ARG188
B:ASP187-B:ARG188
A:ASP176-A:ARG105
B:ASP176-B:ARG105
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP187-A:ARG188
B:ASP187-B:ARG188
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP187-A:ARG40
B:ASP187-B:ARG40
A:ASP197-A:LYS137
B:ASP197-B:LYS137
A:ASP197-A:LYS137
B:ASP197-B:LYS137
A:ASP197-A:ARG131
B:ASP197-B:ARG131
A:ASP216-A:ARG279
B:ASP216-B:ARG279
A:ASP216-A:ARG279
A:ASP197-A:LYS137
B:ASP197-B:LYS137
A:ASP229-A:LYS269
B:ASP229-B:LYS269
A:ASP229-A:LYS269
B:ASP229-B:LYS269
A:ASP229-A:LYS269
B:ASP229-B:LYS269
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP263-A:ARG222
B:ASP263-B:ARG222
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP289-A:ARG131
B:ASP289-B:ARG131
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP34-A:LYS90
B:ASP34-B:LYS90
B:ASP48-B:ARG60
A:ASP289-A:LYS137 A:ASP295-A:ARG298
B:ASP295-B:ARG298
A:ASP34-A:LYS90
B:ASP34-B:LYS90
A:ASP48-A:ARG60
A:ASP48-A:ARG60
B:ASP48-B:ARG60
A:ASP48-A:LYS61
A:ASP48-A:LYS61
A:ASP56-A:ARG60
B:ASP48-B:ARG60 B:ASP56-B:ARG60
A:ASP92-A:ARG76
B:ASP92-B:ARG76
A:ASP56-A:ARG60
B:ASP56-B:ARG60
A:ASP92-A:ARG76
B:ASP92-B:ARG76
A:GLU166-A:HIS172
B:GLU166-B:HIS172
A:ASP92-A:ARG76
B:ASP92-B:ARG76
A:GLU166-A:HIS172
B:GLU166-B:HIS172
A:GLU178-A:ARG105
B:GLU178-B:ARG105
A:GLU166-A:HIS172
B:GLU166-B:HIS172
A:GLU178-A:ARG105
A:GLU178-A:ARG105
B:GLU178-B:ARG105
A:GLU178-A:LYS88
B:ASP56-B:ARG60
A:ASP48-A:ARG60 A:ASP56-A:ARG60
A:GLU178-A:LYS88
B:GLU178-B:LYS88
A:GLU240-A:HIS246
B:GLU240-B:HIS246
A:GLU240-A:HIS246
B:GLU240-B:HIS246
A:GLU240-A:HIS246
B:GLU240-B:HIS246
A:GLU270-A:ARG222
B:GLU270-B:ARG222
A:GLU270-A:ARG222
B:GLU270-B:ARG222
A:GLU270-A:ARG222
B:GLU270-B:ARG222
A:GLU270-A:LYS269
B:GLU270-B:LYS269
A:GLU270-A:LYS269
B:GLU270-B:LYS269
A:GLU270-A:LYS269
B:GLU270-B:LYS269
A:GLU288-A:LYS5
B:GLU288-B:LYS5
A:GLU288-A:LYS137
B:GLU288-B:LYS137
A:GLU288-A:LYS5
B:GLU288-B:LYS5
A:GLU290-A:ARG131
B:GLU290-B:ARG131
A:GLU288-A:LYS5
B:GLU288-B:LYS5
A:GLU290-A:ARG131
B:GLU290-B:ARG131
A:GLU290-A:LYS5
B:GLU290-B:LYS5
A:GLU290-A:ARG131
B:GLU290-B:ARG131
A:GLU290-A:LYS5
B:GLU290-B:LYS5
A:GLU290-A:LYS5
B:GLU290-B:LYS5
A:GLU55-A:ARG40
B:GLU55-B:ARG40
B:GLU55-B:ARG40
A:GLU47-A:ARG60
B:GLU47-B:ARG60
B:GLU47-B:ARG60
B:ASP48-B:LYS61
A:GLU55-A:ARG40
B:GLU55-B:ARG40 B:ASP187-B:HIS41
B:ASP48-B:ARG188
B:GLU178-B:LYS88 B:GLU290-B:LYS137
B:GLU290-B:LYS137
B:GLU290-B:LYS137
B:GLU47-B:HIS41 B:ASP289-B:LYS137
B:GLU288-B:LYS137 B:ASP216-B:ARG279 B:GLU288-B:ARG131
HIS41.NE2-LIG307.O 0.20 ASN142.ND2-LIG307.O8 0.20 SER46.OG-LIG307.O 0.20
LIG307.N6-GLN189.OE1 1.60 THR26.N-LIG307.O7 1.20 TYR118.OH-LIG307.O7 1.20 LIG307.N5-HIS164.O 0.80 HIS41.NE2-LIG307.O 0.80 LIG307.N6-ASN142.OD1 0.60 ASN142.ND2-LIG307.O8 0.60 LIG307.N5-LIG307.O 0.40 GLN189.NE2-LIG307.O8 0.40 LIG307.N6-GLN189.NE2 0.40 HIS163.NE2-LIG307.O8 0.20 LIG307.N6-ASN142.ND2 0.20
GLN192.N-LIG307.O 3.39 GLN192.N-LIG307.O42 2.20 ASN142.ND2-LIG307.O7 1.00 GLN192.N-LIG307.N2 0.60 HIS41.NE2-LIG307.O7 0.60 LIG307.N5-LIG307.O 0.40 GLY143.N-LIG307.O7 0.40 ASN142.ND2-LIG307.C6 0.20 LIG307.N6-ASN142.O 0.20
SER144.OG-LIG307.O8 0.43
ASN142.ND2-LIG307.O8 0.43
LIG307.N6-GLU166.OE1 0.28
CYS145.SG-LIG307.O7 0.14
LIG307.N6-ASN142.ND2 0.14
GLN192.N-LIG307.O42 0.20
GLN189.NE2-LIG307.O 3.59
ASN142.ND2-LIG307.O 0.20
rep3
ASN142.ND2-LIG307.O8 0.20
LIG307.N6-GLN189.OE1 0.20
LIG307.N6-SER46.OG 0.20
LIG307.N6-THR26.O 0.20
GLY143.N-LIG307.O 0.20
SER144.N-LIG307.O7 0.20
LIG307.N6-SER144.OG 0.20
ASN119.ND2-LIG307.O7 0.20
HIS41.NE2-LIG307.O7 0.20
LIG307.N5-HIS164.O 0.20
LIG307.N-GLN189.O 0.40
GLY143.N-LIG307.O7 0.40
HIS41.NE2-LIG307.O 0.40
HIS163.NE2-LIG307.O8 0.40
LIG307.N5-LIG307.O8 0.60
CYS145.SG-LIG307.O 0.60
GLY143.N-LIG307.O8 0.60
ASN142.ND2-LIG307.O 0.80
CYS145.N-LIG307.O7 0.80
LIG307.N5-LIG307.O 0.80
GLN192.N-LIG307.N2 1.00
LIG307.N-GLN192.O 2.20
GLN189.NE2-LIG307.O8 2.59
LIG307.N-GLN189.OE1 5.19
LIG307.N-THR190.O 5.39
GLN189.NE2-LIG307.O 5.99
LIG307.N6-CYS44.O 14.57
SER46.OG-LIG307.O8 17.56
GLU166.N-LIG307.O 42.71
LIG307.N-GLU166.O 51.30
SER46.OG-LIG307.O7 0.20
HIS41.NE2-LIG307.O7 0.20
HIS163.NE2-LIG307.N6 0.40
THR25.OG1-LIG307.O7 0.40
LIG307.N5-HIS164.O 0.40
GLN192.N-LIG307.O1 0.80
LIG307.N-GLN192.O 0.80
GLN192.N-LIG307.N2 1.20
LIG307.N6-LEU141.O 2.00
THR26.N-LIG307.O7 3.19
GLN189.NE2-LIG307.O 3.59
GLN192.N-LIG307.N2 0.57
SER144.N-LIG307.O8 2.56
GLN192.N-LIG307.N2 0.20
GLY143.N-LIG307.O8 4.59
LIG307.N5-LIG307.O 4.99
CYS145.N-LIG307.O8 1.14
HIS41.NE2-LIG307.O7 4.84
LIG307.N-THR190.O 1.80
LIG307.N-GLN189.OE1 2.20
LIG307.N6-GLU166.OE1 5.79
SER144.N-LIG307.O8 5.59
GLY143.N-LIG307.O8 1.80
LIG307.N6-ASN142.OD1 5.12
LIG307.N6-PHE140.O 3.59
LIG307.N5-LIG307.O8 3.59
LIG307.N6-GLU166.OE2 7.39
CYS145.N-LIG307.O8 5.79
LIG307.N-THR190.O 7.78
LIG307.N6-SER144.OG 13.17
LIG307.N-GLN189.OE1 3.79
GLN189.NE2-LIG307.O 11.81
GLN189.NE2-LIG307.O 5.99
SER46.OG-LIG307.O8 4.19
GLN192.NE2-LIG307.O 9.58
LIG307.N-THR190.O 8.58
GLU166.N-LIG307.O 31.74 LIG307.N-GLN189.OE1 13.77
LIG307.N-LIG307.O 2.00
GLY143.N-LIG307.O8 15.50
LIG307.N-GLN192.O 7.39
LIG307.N6-CYS44.O 12.18
ASN142.ND2-LIG307.O8 9.58
rep2 LIG307.N-GLU166.O 45.11
CYS145.N-LIG307.O7 3.79
LIG307.N-GLN189.OE1 32.43
LIG307.N-GLN192.O 17.92
HIS163.ND1-LIG307.O8 29.54
LIG307.N-GLN189.OE1 21.16
LIG307.N-GLN192.O 9.98
GLU166.N-LIG307.O 36.73 GLN189.NE2-LIG307.O 17.17
LIG307.N-ARG188.O 26.35
LIG307.N-GLU166.O 30.54
GLU166.N-LIG307.O 45.23
LIG307.N5-HIS164.O 37.70
LIG307.N5-HIS164.O 44.71
LIG307.N-GLU166.O 40.92
SARS-CoV-2-N3 rep1 LIG307.N-GLU166.O 55.69
rep3 LIG307.N5-HIS164.O 46.31
rep2
LIG307.N-GLU166.O 55.33
SARS-CoV-1-N3 rep1
GLU166.N-LIG307.O 54.09
Table 2.36 The MD-HBs linking the ligand LIG307 of monomeric the SARS-CoV-1-Mpro-N3-2hob model (denoted as “SARS-CoV-1-N3 monomer”) and the SARS-CoV-2-Mpro-N3-6lu7 model (denoted as “SARS-CoV-2-N3 monomer”), where each model has three sets of MD simulations [346]
2.4 Concluding Remarks 123
HIS163.N-SER147.O 60.68 TYR54.OH-ASP187.O 58.08 LEU167.N-VAL171.O 56.09 THR257.OG1-LEU253.O 55.89 LEU87.N-CYS38.O 55.69
VAL36.N-LEU89.O 58.28 VAL20.N-LEU27.O 55.09 TRP31.N-CYS16.O 54.49 LEU87.N-CYS38.O 54.09 VAL114.N-TYR126.O 53.09 HIS163.N-SER147.O 53.09
TRP31.N-CYS16.O 59.46
VAL36.N-LEU89.O 59.46
VAL20.N-LEU27.O 58.75
ILE136.N-HIS172.O 57.75
TYR182.OH-CYS160.O 57.75
HIS163.N-SER147.O 57.61
THR257.OG1-LEU253.O 57.04
VAL114.N-TYR126.O 55.48
ARG131.N-THR135.O 55.48
LEU87.N-CYS38.O 55.05
TRP31.N-CYS16.O 57.09
VAL36.N-LEU89.O 56.89
THR257.OG1-LEU253.O 56.29
LEU167.N-VAL171.O 55.69
ASP153.N-CYS156.O 54.29
THR135.OG1-ASN133.OD1 54.09
ARG88.N-SER81.O 54.09
LEU89.N-VAL36.O 53.49
TYR37.N-LEU30.O 52.50
VAL114.N-TYR126.O 52.10
LEU167.N-VAL171.O 49.93
VAL157.N-LYS100.O 49.79
ASN95.N-ASP33.O 48.10
LYS90.N-GLY79.O 47.31
GLN192.NE2-VAL186.O 47.31
VAL18.N-GLY29.O 47.50 ALA173.N-MET165.O 47.31 TYR182.N-GLY174.O 47.31
THR21.N-LEU67.O 44.71 CYS128.N-PHE112.O 44.11 ALA70.N-VAL73.O 43.71
SER113.OG-GLN127.OE1 48.36
GLY149.N-TYR161.O 48.08
LEU242.N-ASN231.OD1 47.94
ASN231.N-LEU227.O 47.80
LEU75.N-VAL68.O 47.11
PHE150.N-SER113.O 46.51
CYS22.N-THR25.O 46.11
ALA70.N-VAL73.O 45.91
GLN83.N-VAL86.O 46.91
ASP153.N-CYS156.O 47.70
GLY149.N-TYR161.O 44.71
ALA70.N-VAL73.O 49.36
PHE150.N-SER113.O 43.31
GLN192.NE2-VAL186.O 48.30
LEU27.N-VAL20.O 45.31
VAL20.N-LEU27.O 48.30
ARG88.N-SER81.O 50.50
ASN84.ND2-GLU178.O 48.50
LEU115.N-VAL148.O 50.70
LYS90.N-GLY79.O 50.64
LEU242.N-ASN231.OD1 48.90 GLN192.NE2-VAL186.O 45.31
THR135.OG1-ASN133.OD1 51.90
TYR37.N-LEU30.O 47.90
THR25.OG1-CYS44.O 51.64
HIS172.N-ILE136.O 48.90 LEU75.N-VAL68.O 46.51
VAL114.N-TYR126.O 52.10
PHE112.N-CYS128.O 48.90
HIS172.N-ILE136.O 53.20
VAL157.N-LYS100.O 51.70 TYR37.N-LEU30.O 50.90
LYS88.N-SER81.O 52.50
ARG131.N-THR135.O 51.30
LEU89.N-VAL36.O 53.34
LEU87.N-CYS38.O 51.90
TYR54.OH-ASP187.O 47.31
GLY146.N-HIS163.O 53.29
LYS90.N-GLY79.O 51.50
GLN19.N-GLN69.O 53.49
VAL36.N-LEU89.O 54.69
ARG88.N-SER81.O 52.30 VAL157.N-LYS100.O 53.49
LEU27.N-VAL20.O 55.29
ALA173.N-MET165.O 52.30 HIS172.N-ILE136.O 52.10
SER147.OG-SER144.O 55.69
LEU89.N-VAL36.O 52.89
ILE78.N-LYS90.O 56.69
TYR182.OH-CYS160.O 62.48
VAL20.N-LEU27.O 59.28
THR201.OG1-GLU240.O 62.48
THR257.OG1-LEU253.O 60.28
THR135.OG1-ASN133.OD1 60.74
THR201.OG1-GLU240.O 61.68
THR201.OG1-GLU240.O 62.59
ILE78.N-LYS90.O 61.68
THR201.OG1-GLU240.O 61.08
TYR209.OH-ILE259.O 63.67 SER267.OG-ASP263.O 63.07
TYR182.OH-ILE106.O 66.27 ILE78.N-LYS90.O 64.87
TYR54.OH-ASP187.O 66.00
TYR209.OH-ILE259.O 63.87
TYR182.OH-CYS160.O 62.87
TYR54.OH-ASP187.O 62.48
SARS-CoV-2-N3 rep1 TRP31.N-CYS16.O 65.27
TYR209.OH-ILE259.O 66.67
rep2
ILE78.N-LYS90.O 67.43
SARS-CoV-1-N3 rep1
TYR209.OH-ILE259.O 66.47
rep3
VAL157.N-LYS100.O 46.31
THR175.OG1-ASP176.O 47.11
LEU115.N-VAL148.O 47.31
VAL20.N-LEU27.O 47.70
THR135.OG1-ASN133.OD1 47.70
LEU75.N-VAL68.O 47.90
GLN19.N-GLN69.O 48.30
LEU89.N-VAL36.O 48.90
ASN95.N-ASP33.O 48.90
ALA70.N-VAL73.O 49.10
ARG131.N-THR135.O 49.10
TYR37.N-LEU30.O 49.70
LYS88.N-SER81.O 50.70
VAL36.N-LEU89.O 52.69
VAL114.N-TYR126.O 53.69
THR201.OG1-GLU240.O 54.89
ASN203.ND2-ASP289.O 55.69
THR257.OG1-LEU253.O 56.29
TRP31.N-CYS16.O 56.49
SER144.OG-LEU141.O 56.89
LEU87.N-CYS38.O 57.09
LEU167.N-VAL171.O 58.08
GLY146.N-HIS163.O 59.08
HIS163.N-SER147.O 62.28
ILE78.N-LYS90.O 63.27
TYR182.OH-CYS160.O 63.67
SER267.OG-ASP263.O 65.87
TYR209.OH-ILE259.O 70.66
rep2
LYS90.N-GLY79.O 45.11
ASN95.N-ASP33.O 45.11
VAL36.N-LEU89.O 45.31
VAL157.N-LYS100.O 45.31
GLY146.N-HIS163.O 45.51
GLN189.N-MET49.O 45.91
TYR37.N-LEU30.O 46.11
CYS128.N-PHE112.O 46.11
THR21.N-LEU67.O 46.51
ASP153.N-CYS156.O 46.71
LYS88.N-SER81.O 47.50
GLN192.NE2-VAL186.O 48.70
GLN83.N-VAL86.O 48.70
SER144.OG-LEU141.O 48.70
HIS163.N-SER147.O 49.70
LEU87.N-CYS38.O 50.90
LEU167.N-VAL171.O 51.90
TYR182.OH-CYS160.O 55.09
THR257.OG1-LEU253.O 56.89
THR135.OG1-ASN133.OD1 57.09
ARG131.N-THR135.O 57.09
VAL20.N-LEU27.O 58.28
TYR54.OH-ASP187.O 59.68
THR201.OG1-GLU240.O 61.68
TRP31.N-CYS16.O 61.88
TYR209.OH-ILE259.O 67.27
ILE78.N-LYS90.O 68.06
SER267.OG-ASP263.O 70.66
rep3
Table 2.37 The MD-HBs (with occupancy rates ≥20%) of monomeric the SARS-CoV-1-Mpro-N3-2hob model (denoted as “SARS-CoV-1-N3 monomer”) and the SARS-CoV-2-Mpro-N3-6lu7 model (denoted as “SARS-CoV-2-N3 monomer”), where each model has three sets of MD simulations [346]
124 2 3C-Like Protease (3CLpro)
SER123.N-ALA116.O 43.51
VAL297.N-PRO293.O 32.86
ASN231.ND2-LEU242.O 32.72
ASN95.ND2-TRP31.O 33.93
ALA173.N-MET165.O 33.53
TYR118.N-SER121.O 33.73 ARG105.NH2-PHE181.O 33.73
LYS269.N-CYS265.O 30.94 THR45.OG1-ASP48.OD1 30.74
ASN95.ND2-TRP31.O 33.93
TYR239.N-ALA234.O 30.94
LEU27.N-VAL20.O 34.14
GLY149.N-TYR161.O 34.13
CYS22.N-THR25.O 31.54
GLN83.N-LEU86.O 34.53
ARG40.NH2-ASP187.OD1 34.93
VAL91.N-ASP34.O 31.74
TYR239.N-ALA234.O 35.28
LEU30.N-TYR37.O 34.28
CYS22.N-THR25.O 35.93 LEU32.N-VAL35.O 35.73
HIS80.ND1-ASN63.OD1 32.93 TRP218.NE1-THR280.O 31.94
THR292.OG1-ASP295.OD1 36.42
THR199.N-ASN238.O 36.27
TYR239.N-ALA234.O 35.93
THR45.OG1-ASP48.OD1 34.93
PHE8.N-SER113.OG 34.73
THR292.OG1-ASP295.OD2 36.73 TYR239.N-ALA234.O 36.73
ILE136.N-HIS172.O 34.53 ASN95.ND2-TRP31.O 33.13
LYS137.N-ALA129.O 37.98
THR45.OG1-ASP48.OD1 36.56
HIS164.N-ALA173.O 37.52
GLU14.N-SER10.O 37.33
GLY149.N-TYR161.O 34.53
CYS128.N-PHE112.O 39.32 LEU242.N-ASN231.OD1 39.12 PHE150.N-SER113.O 37.52
ASN231.N-LEU227.O 36.13 SER123.N-ALA116.O 35.73 GLN69.N-GLN19.O 35.33
CYS128.N-PHE112.O 38.41
THR21.N-LEU67.O 38.26
PHE8.N-SER113.OG 37.98
LEU27.N-VAL20.O 38.52
VAL18.N-GLY29.O 38.12
LEU30.N-TYR37.O 38.72
ASN231.N-LEU227.O 39.52 THR199.N-ASN238.O 39.52
ASP153.N-CYS156.O 36.93 LEU242.N-ASN231.OD1 36.53
LEU32.N-THR35.O 39.69
LEU205.N-THR201.O 38.83
GLY109.N-MET130.O 39.12
GLN189.N-MET49.O 39.72 ALA70.N-VAL73.O 39.52
LEU30.N-TYR37.O 37.52 LEU268.N-MET264.O 37.13
TYR182.N-GLY174.O 39.12
ASN203.ND2-ASP289.O 41.54
SER147.OG-SER144.O 40.68
LEU32.N-THR35.O 39.12
ASN133.ND2-GLY195.O 39.12
LEU205.N-THR201.O 40.52
THR199.N-ASN238.O 39.72
SER147.OG-SER144.O 37.92
CYS22.N-THR25.O 42.25
THR175.OG1-ASP176.O 39.72
GLU14.N-SER10.O 41.12
THR199.N-ASN238.O 38.32
TYR182.N-GLY174.O 41.68
GLN192.NE2-VAL186.O 42.39
TYR118.N-SER121.O 41.12
VAL91.N-ASP34.O 41.32
TYR118.N-SER121.O 38.92 THR25.OG1-CYS44.O 41.12
ASN95.N-ASP33.O 42.96
THR21.N-LEU67.O 41.72
LEU30.N-TYR37.O 41.92
LYS90.N-GLY79.O 42.91
ASN84.ND2-GLU178.O 39.92
THR135.OG1-ASN133.OD1 40.52
ASN151.N-SER158.O 38.12
ARG105.NH2-PHE181.O 43.39
SER144.OG-LEU141.O 43.39
ARG105.NH2-PHE181.O 42.32
GLN19.N-GLN69.O 42.12
ASN203.ND2-ASP289.O 43.31 HIS172.N-ILE136.O 42.91
LEU205.N-THR201.O 41.12 LEU115.N-VAL148.O 40.72 LEU32.N-THR35.O 40.52
GLN189.N-MET49.O 45.38
LEU75.N-VAL68.O 44.38
GLN299.NE2-ARG4.O 43.39
THR292.OG1-ASP295.OD1 43.71
LEU205.N-THR201.O 43.51
SER123.N-ALA116.O 42.91
ASN95.N-ASP33.O 45.71 GLN19.N-GLN69.O 45.51
GLN83.N-LEU86.O 41.32 GLN19.N-GLN69.O 41.12
GLN299.NE2-ASP295.O 46.37
ASN133.ND2-GLY195.O 46.23
ARG131.N-THR135.O 44.31
ASN231.N-LEU227.O 44.11
LEU89.N-VAL36.O 46.11 PHE112.N-CYS128.O 45.91
VAL157.N-LYS100.O 42.51 ASN95.N-ASP33.O 41.72
TYR37.N-LEU30.O 46.66
ASP153.N-CYS156.O 46.37
CYS128.N-PHE112.O 45.31
THR175.OG1-ASP176.O 46.51 LEU75.N-VAL68.O 46.11
GLY109.N-MET130.O 43.11 ASN203.ND2-ASP289.O 43.11
THR25.OG1-CYS44.O 44.31
PHE150.N-SER113.O 47.80
ASN84.ND2-GLU178.O 47.08
LEU115.N-VAL148.O 45.71
SER147.OG-SER144.O 45.71
VAL91.N-ASP34.O 45.31
ASN84.ND2-GLU178.O 32.73
TYR182.N-GLY174.O 33.13
SER113.OG-GLN127.OE1 33.13
TYR118.N-SER121.O 33.53
PHE150.N-SER113.O 34.53
TYR239.N-ALA234.O 35.13
ASN95.ND2-TRP31.O 35.13
SER10.OG-GLU14.OE1 35.33
ALA173.N-MET165.O 35.93
LEU67.N-THR21.O 36.33
SER147.OG-SER144.O 36.53
ASN231.N-LEU227.O 36.73
ASN151.N-SER158.O 36.73
ASN28.ND2-CYS145.O 37.52
LEU268.N-MET264.O 37.52
THR199.N-ASN238.O 37.92
ASN203.ND2-GLY109.O 38.32
ASP153.N-CYS156.O 38.52
GLY149.N-TYR161.O 38.72
VAL18.N-GLY29.O 38.92
CYS128.N-PHE112.O 39.72
LEU32.N-VAL35.O 39.92
LEU30.N-TYR37.O 39.92
LEU242.N-ASN231.OD1 40.12
GLN83.N-VAL86.O 40.32
PHE8.N-SER113.OG 40.52
LYS90.N-GLY79.O 42.71
PHE112.N-CYS128.O 42.91
GLU14.N-SER10.O 43.31
GLN192.NE2-VAL186.O 44.71
LEU75.N-VAL68.O 44.91
SER113.N-PHE150.O 34.33
HIS80.ND1-ASN63.OD1 34.93
ASN203.ND2-ASP289.O 35.33
LYS137.N-ALA129.O 36.13
ASN133.ND2-GLY195.O 37.33
TYR118.N-SER121.O 37.92
ASN84.ND2-GLU178.O 38.12
LEU242.N-ASN231.OD1 38.52
ALA116.N-GLY124.O 38.72
THR25.OG1-CYS44.O 39.32
LEU32.N-VAL35.O 39.32
LEU89.N-VAL36.O 39.92
VAL91.N-ASP34.O 39.92
SER123.N-ALA116.O 39.92
TYR182.N-GLY174.O 40.52
GLN19.N-GLN69.O 40.52
ARG40.NH2-ASP187.OD2 40.72
TYR239.N-ALA234.O 40.72
SER147.OG-SER144.O 40.92
GLN69.N-GLN19.O 41.12
CYS22.N-THR25.O 41.72
ALA70.N-VAL73.O 41.72
PHE150.N-SER113.O 42.32
THR175.OG1-ASP176.O 42.71
LEU205.N-THR201.O 43.31
GLY149.N-TYR161.O 43.71
LEU27.N-VAL20.O 43.71
ARG40.NE-ASP187.OD1 44.31
VAL114.N-TYR126.O 44.31
ILE136.N-HIS172.O 44.51
2.4 Concluding Remarks 125
ARG40.NE-ASP187.OD2 31.54 LYS269.N-CYS265.O 31.34 LEU268.N-MET264.O 30.94
THR292.OG1-ASP295.OD1 29.14 LYS180.N-ASP176.OD1 28.94 THR25.OG1-CYS44.O 28.74
ILE281.N-SER284.O 32.01
LEU57.N-ASN53.O 31.58
LYS102.N-VAL157.O 31.44
LEU67.N-THR21.O 31.44
VAL91.N-ASP34.O 31.29
HIS80.ND1-ASN63.OD1 31.01
ALA210.N-ALA206.O 30.58
SER254.OG-ILE259.O 30.58
SER158.N-ASN151.O 30.44
ALA116.N-GLY124.O 30.44
PHE112.N-CYS128.O 30.16
TYR101.OH-ASP33.OD1 30.01
ASN151.N-SER158.O 32.53
PHE112.N-CYS128.O 31.34
LEU268.N-MET264.O 30.54
ILE200.N-ASP289.OD2 29.94
THR111.OG1-ASP295.OD1 29.54
SER81.N-ARG88.O 29.54
ILE281.N-SER284.O 29.54
ASN231.ND2-LEU242.O 29.34
TRP218.NE1-THR280.O 29.34
MET130.N-GLN110.O 28.94
CYS160.N-GLY149.O 28.34
HIS80.ND1-ASN63.OD1 28.14
ASN28.ND2-CYS145.O 33.33
LYS102.N-VAL157.O 29.34 CYS160.N-GLY149.O 28.74 LEU67.N-THR21.O 28.14 ASN151.N-SER158.O 27.94 SER144.OG-LEU141.O 27.94 GLY109.N-MET130.O 27.74 LEU57.N-ASN53.O 27.35 VAL86.N-GLN83.O 27.15 SER254.OG-ILE259.O 27.15 SER10.OG-GLU14.OE2 26.95 SER301.N-GLY2.O 26.95 VAL104.N-PHE159.O 26.35 SER62.N-ASN65.OD1 26.15 SER113.N-PHE150.O 25.95
SER81.N-ARG88.O 27.74 TYR126.N-VAL114.O 27.74 THR198.OG1-GLU240.OE1 27.35 ALA255.N-GLY251.O 26.35 THR198.OG1-GLU240.OE2 26.15 MET162.N-THR175.O 24.55 ALA234.N-PHE230.O 24.55 THR21.OG1-THR26.OG1 24.35 ARG105.NH1-ASP176.OD2 23.95 ASN231.ND2-LEU242.O 23.35 ASN28.ND2-CYS145.O 23.35 VAL104.N-PHE159.O 22.95 CYS160.N-GLY149.O 22.75 LEU167.N-VAL171.O 22.75 ASP216.N-ALA211.O 22.55
THR175.OG1-ASP176.O 29.73
ILE200.N-ASP289.OD2 29.73
TRP218.NE1-THR280.O 29.73
SER123.N-ALA116.O 29.16
ASN95.ND2-TRP31.O 29.16
LEU268.N-MET264.O 28.31
GLN83.N-LEU86.O 28.17
THR21.OG1-THR26.OG1 28.17
LYS180.N-ASP176.OD1 28.02
ALA255.N-GLY251.O 28.02
LEU115.N-VAL148.O 28.02
SER81.N-ARG88.O 27.45
THR292.OG1-ASP295.OD2 27.45
ASN151.N-SER158.O 27.03
VAL104.N-PHE159.O 26.74
GLY109.N-MET130.O 26.74
GLY146.N-HIS163.O 26.46
ARG40.NE-ASP187.OD2 25.32
LYS269.N-CYS265.O 25.32
GLN107.N-GLN110.OE1 25.18
ALA173.N-MET165.O 24.89
VAL91.N-ASP34.O 27.94
THR45.OG1-ASP48.OD2 27.54
LYS269.N-CYS265.O 27.15
SER158.N-ASN151.O 26.95
SER113.OG-GLN127.OE1 26.75
SER10.OG-GLU14.OE2 26.75
THR175.N-MET162.O 26.55
LYS102.N-VAL157.O 26.15
LEU67.N-THR21.O 25.75
ASN28.ND2-CYS145.O 25.75
ASN203.ND2-GLY109.O 25.55
THR292.N-ASP295.OD1 25.55
PHE305.N-TYR154.O 25.15
SER113.N-PHE150.O 24.75
SER10.OG-GLU14.OE1 24.55
ILE136.N-HIS172.O 24.15
LYS180.N-ASP176.OD2 23.95
GLN273.N-LYS269.O 22.75
THR21.OG1-THR26.OG1 21.96
GLY29.N-VAL18.O 21.76
TYR209.N-LEU205.O 24.35 THR45.OG1-ASP48.OD2 24.15
TYR101.OH-ASP33.OD1 21.56 ARG40.NE-ASP187.OD1 21.56
GLN273.N-LYS269.O 24.95
THR292.N-ASP295.OD1 22.16
ASN65.N-SER62.O 24.55
ALA210.N-ALA206.O 24.95
ALA210.N-ALA206.O 22.55 VAL303.N-GLN256.OE1 21.76
ASN221.N-SER267.OG 25.55
THR175.N-MET162.O 22.55
ARG40.NH2-ASP187.OD2 27.54
SER10.OG-GLU14.OE1 30.14
THR292.OG1-ASP295.OD1 30.54
SER113.N-PHE150.O 27.94 LEU67.N-THR21.O 27.94
THR243.OG1-HIS246.ND1 30.54
ARG105.NH2-PHE181.O 28.14
ARG131.N-THR135.O 32.34
ASN133.ND2-GLY195.O 30.94
ASN84.ND2-GLU178.O 32.73
GLY146.N-HIS163.O 29.74 THR45.OG1-ASP48.OD2 29.54
SER158.N-ASN151.O 28.54
THR45.OG1-ASP48.OD1 32.93
ILE281.N-SER284.O 32.93
GLN256.NE2-PRO252.O 29.94
GLN299.N-ASP295.O 30.54
ILE281.N-SER284.O 30.54
SARS-CoV-2-N3 rep1 THR21.N-LEU67.O 33.53
GLN69.N-GLN19.O 33.13
rep3 VAL18.N-GLY29.O 30.54
rep2
CYS160.N-GLY149.O 32.43
SARS-CoV-1-N3 rep1
ASN203.ND2-ASP289.O 33.53
LEU208.N-VAL204.O 23.55
ALA234.N-PHE230.O 23.95
GLY23.N-VAL42.O 24.15
THR243.OG1-HIS246.ND1 24.15
ASN214.N-ALA210.O 24.35
VAL86.N-GLN83.O 24.75
SER62.N-ASN65.OD1 24.95
LYS137.N-ALA129.O 25.35
SER81.N-LYS88.O 25.35
THR198.OG1-GLU240.OE1 25.95
ARG105.NH2-PHE181.O 25.95
ASN180.N-ASP176.OD2 26.15
LYS102.N-VAL157.O 26.95
ALA116.N-GLY124.O 27.15
THR198.OG1-GLU240.OE2 27.54
THR21.OG1-THR25.O 27.74
SER10.OG-GLU14.OE2 27.74
GLU290.N-GLU288.OE1 28.34
SER158.N-ASN151.O 28.34
ALA255.N-GLY251.O 28.54
LYS269.N-CYS265.O 28.74
SER113.N-PHE150.O 28.94
ASN231.ND2-LEU242.O 29.14
SER123.N-ALA116.O 29.14
CYS160.N-GLY149.O 29.54
GLN256.NE2-PRO252.O 30.14
THR292.OG1-ASP295.OD2 30.54
VAL303.N-GLN256.OE1 31.14
ASN133.ND2-GLY195.O 31.54
ARG40.NE-ASP187.OD2 31.74
ARG40.NH2-ASP187.OD1 31.74
HIS80.ND1-ASN63.OD1 32.34
LEU27.N-VAL20.O 32.53
ILE281.N-SER284.O 32.53
rep2
SER10.OG-GLU14.OE2 25.55
ALA210.N-ALA206.O 25.55
GLN107.N-GLN110.OE1 25.75
THR98.OG1-ASP33.OD1 25.75
ASN95.ND2-TRP31.O 25.75
TYR209.N-LEU205.O 25.95
ILE281.N-SER284.O 25.95
VAL18.N-GLY29.O 26.15
THR292.OG1-ASP295.OD1 26.15
SER62.N-ASN65.OD1 26.35
ALA173.N-MET165.O 26.55
LEU30.N-TYR37.O 26.75
ASN151.ND2-THR111.O 26.95
ALA255.N-GLY251.O 26.95
THR243.OG1-HIS246.ND1 27.35
CYS160.N-GLY149.O 27.74
LEU268.N-MET264.O 28.14
HIS172.N-ILE136.O 28.34
THR198.OG1-GLU240.OE1 28.54
SER113.OG-GLN127.OE1 28.54
GLU14.N-SER10.O 28.94
GLY109.N-MET130.O 29.14
LYS102.N-VAL157.O 29.34
VAL86.N-GLN83.O 29.74
HIS41.NE2-HIS164.O 30.14
LYS269.N-CYS265.O 30.34
TRP218.NE1-THR280.O 30.74
ARG105.NH2-PHE181.O 30.94
SER158.N-ASN151.O 31.34
PHE112.N-CYS128.O 31.74
TYR126.N-VAL114.O 32.93
THR199.N-ASN238.O 33.93
ASN231.N-LEU227.O 33.93
PHE8.N-SER113.OG 34.33
rep3
Table 2.38 The MD-HBs (with occupancy rates ≥20%) of monomeric the SARS-CoV-1-Mpro-N3-2hob model (denoted as “SARS-CoV-1-N3 monomer”) and the SARS-CoV-2-Mpro-N3-6lu7 model (denoted as “SARS-CoV-2-N3 monomer”), where each model has three sets of MD simulations [346] (continuation)
126 2 3C-Like Protease (3CLpro)
GLY120.N-ASN28.OD1 20.76 GLN107.N-GLN110.OE1 20.76 THR292.N-ASP295.OD2 20.56
ASN180.N-ASP176.OD1 21.56 ARG105.NH1-ASN180.O 21.56 ASN231.ND2-LEU242.O 21.3 SER158.N-ASN151.O 21.36 SER284.N-ILE281.O 21.16
VAL186.N-GLN192.OE1 22.05
SER10.OG-GLU14.OE2 21.91
ASP92.N-ARG76.O 21.76
THR292.N-ASP295.OD1 21.76
THR198.OG1-GLU240.OE1 21.62
ASN180.N-ASP176.OD2 20.76
ASN65.N-SER62.O 20.16
THR224.OG1-ASP263.OD2 20.20
SER121.N-TYR118.O 20.06
LEU208.N-VAL204.O 20.56 ASP216.N-ALA211.O 20.16
MET130.N-GLN110.O 20.63
ASN238.ND2-ASP197.O 20.34
THR226.OG1-ASP229.OD1 20.56
GLN299.NE2-ASP295.O 20.56
LYS90.NZ-THR35.OG1 20.63
TYR209.N-LEU205.O 21.05
THR198.OG1-GLU240.OE2 20.76 ASN151.N-SER158.O 20.76
PHE8.N-SER113.OG 20.56 THR198.OG1-GLU240.OE2 20.56
THR292.OG1-ASP295.OD2 20.76
THR111.OG1-ASP295.OD2 20.96
SER254.OG-ILE259.O 21.16
THR21.OG1-THR26.OG1 23.35
SER81.N-LYS88.O 23.55
THR292.N-ASP295.OD1 23.55
ASN180.N-ASP176.OD1 23.55
ILE200.N-ASP289.OD1 24.15
LEU272.N-LEU268.O 24.35
SER113.N-PHE150.O 21.19
GLN273.N-LYS269.O 20.96
ASN231.ND2-LEU242.O 24.35
VAL104.N-PHE159.O 24.35
THR45.OG1-ASP48.OD1 24.55
LEU57.N-ASN53.O 24.75
THR45.OG1-ASP48.OD2 24.95
THR111.OG1-ASP295.OD1 24.95
THR26.OG1-THR21.OG1 24.95
GLN299.NE2-ASP295.O 25.15
SER10.OG-GLU14.OE1 25.35
SER10.OG-GLU14.OE1 21.19
VAL186.N-GLN192.OE1 20.76
GLN69.N-GLN19.O 20.76
GLN107.N-GLN110.OE1 21.76
THR224.OG1-ASP263.OD1 20.16
LYS180.N-ASP176.OD2 22.19
GLU14.N-SER10.O 21.34
GLN299.N-ASP295.O 20.96
ASN180.N-ASP176.OD2 21.96
SER254.OG-ILE259.O 20.36
ARG105.NH1-ASP176.OD2 22.33
ASP92.N-ARG76.O 20.96
LYS5.NZ-GLU288.OE2 21.36
TRP218.NE1-THR280.O 21.96
ARG105.NH1-ASP176.OD1 20.16
ARG298.N-PHE294.O 21.36
LEU208.N-VAL204.O 20.36
THR45.OG1-ASP48.OD2 23.04
TYR209.N-LEU205.O 20.36
ARG298.NH2-ASP295.OD1 21.96
TYR126.N-VAL114.O 22.48
LEU208.N-VAL204.O 22.75
TYR209.N-LEU205.O 20.56
SER254.N-LEU250.O 23.90
ALA234.N-PHE230.O 20.36
SER254.OG-ILE259.O 21.96
ASN151.ND2-THR111.O 22.55
ARG105.NH1-ASP176.OD1 22.16
ALA116.N-GLY124.O 23.35
ALA116.N-GLY124.O 20.56
ASP216.N-ALA211.O 24.32
ASN51.ND2-ASP48.O 20.76
THR175.OG1-ASP176.O 20.36
ALA255.N-GLY251.O 23.55
ARG60.NH1-ASP48.OD2 20.76
ALA234.N-PHE230.O 24.75
TYR101.OH-ASP33.OD2 20.96
ILE136.N-HIS172.O 22.95
GLN83.NE2-GLU178.O 22.62
ARG40.NE-ASP187.OD1 23.75
MET165.N-ALA173.O 20.96
LEU141.N-TYR118.OH 24.75
THR198.OG1-GLU240.OE2 21.16
VAL104.N-PHE159.O 22.95
SER81.N-LYS88.O 22.75
HIS41.NE2-HIS164.O 23.95
LEU86.N-GLN83.O 21.16
GLN69.N-GLN19.O 24.75
TYR101.OH-ASP33.OD1 21.36
THR111.OG1-ASP295.OD2 23.35
ASN221.N-SER267.OG 23.55
MET6.N-GLN299.OE1 20.56
GLY120.N-ASN28.OD1 23.95
LYS102.N-VAL157.O 21.16
TYR118.N-SER121.O 24.75
TYR126.N-VAL114.O 24.15
MET130.N-GLN110.O 21.36
ASN28.ND2-CYS145.O 24.89
ALA210.N-ALA206.O 21.76
ALA116.N-GLY124.O 21.36
2.4 Concluding Remarks 127
128
2 3C-Like Protease (3CLpro)
Table 2.39 The MD-HBs linking the ligands LIG307 and LIG308 of dimer the SARS-CoV-1Mpro-N3-2hob model (denoted as “SARS-CoV-1-N3 dimer”) —the model has three sets of MD simulations [346] SARS-CoV-1-N3 rep1
rep2
rep3
LIG307.N-B:GLU166.O 45.22%
B:GLU166.N-LIG307.O 53.78%
A:SER144.N-LIG308.O8 27.09%
B:GLU166.N-LIG307.O 29.28%
LIG307.N5-B:HIS164.O 42.43%
LIG308.N-A:ARG188.O 23.90%
LIG307.N-B:GLN189.OE1 25.50%
LIG307.N-B:GLU166.O 40.24%
A:GLN189.NE2-LIG308.O 18.92%
B:SER144.N-LIG307.O8 23.71%
LIG307.N-B:GLN189.OE1 33.86%
A:GLY143.N-LIG308.O8 11.16%
B:GLY143.N-LIG307.O8 14.74%
B:CYS145.N-LIG307.O7 11.95%
LIG308.N-LIG308.O42 9.96%
LIG307.N5-LIG307.O 9.16%
B:ASN142.ND2-LIG307.O8 9.76%
LIG308.N6-A:LEU141.O 5.38%
LIG307.N-B:THR190.O 8.17%
LIG307.N-B:GLN192.O 5.38%
LIG308.N-LIG308.O 5.38%
LIG307.N6-B:LEU141.O 4.98%
B:THR190.N-LIG307.O 4.38%
LIG308.N-A:GLU166.O 4.58%
B:GLN189.NE2-LIG307.O 4.38%
B:GLN189.NE2-LIG307.O 4.18%
A:GLU166.N-LIG308.O 2.79%
B:CYS145.N-LIG307.O7 3.98%
LIG307.N-B:THR190.O 1.59%
A:CYS145.N-LIG308.O7 2.79%
B:SER144.OG-LIG307.O8 3.19%
LIG307.N6-B:GLU166.OE2 1.20%
LIG308.N-A:GLN189.OE1 2.59%
LIG307.N5-B:HIS164.O 1.79%
LIG307.N-LIG307.O 1.00%
A:SER144.OG-LIG308.O8 1.59%
LIG307.N6-B:SER144.OG 1.59%
LIG307.N6-B:PHE140.O 0.60%
LIG308.N-A:THR190.O 1.20%
B:GLN192.N-LIG307.N2 0.80%
B:GLN192.N-LIG307.N2 0.40%
A:HIS41.NE2-LIG308.O7 1.00%
LIG307.N6-B:GLU166.OE1 0.60%
LIG307.N6-B:GLU166.OE1 0.40%
A:HIS41.NE2-LIG308.O 1.00%
LIG307.N-B:GLN192.O 0.40%
B:THR190.OG1-LIG307.O 0.20%
LIG308.N6-A:SER144.OG 0.80%
B:HIS41.NE2-LIG307.O 0.40%
LIG307.N6-B:SER144.OG 0.20%
A:GLN192.NE2-LIG308.N2 0.80%
B:GLN192.N-LIG307.O1 0.20%
LIG308.N6-A:PHE140.O 0.60%
B:ASN119.ND2-LIG307.C2 0.20%
A:GLU166.N-LIG308.O 43.82%
A:GLN189.NE2-LIG308.O42 0.60%
LIG307.N-B:GLN189.O 0.20%
LIG308.N-A:GLU166.O 32.87%
LIG308.N5-A:ASN142.OD1 0.40%
LIG308.N-A:GLN189.OE1 21.51%
A:THR190.N-LIG308.O 0.40%
A:GLU166.N-LIG308.O 51.79%
LIG308.N5-A:HIS164.O 17.73%
A:GLN192.N-LIG308.N2 0.20%
LIG308.N-A:GLU166.O 39.64%
A:CYS145.N-LIG308.O7 13.15%
LIG308.N-A:GLN192.O 0.20%
LIG308.N-A:GLN189.OE1 34.26%
LIG308.N-A:THR190.O 9.36%
A:GLN192.NE2-LIG308.O1 0.20%
LIG308.N5-A:HIS164.O 21.71%
LIG308.N6-A:GLU166.OE2 4.58%
A:ASN119.ND2-LIG308.C2 0.20%
LIG308.N-A:THR190.O 10.56%
LIG308.N6-A:GLU166.OE1 3.78%
A:THR26.OG1-LIG308.C4 0.20%
A:CYS145.N-LIG308.O7 10.16%
A:THR190.N-LIG308.O 3.19%
A:CYS145.N-LIG308.O8 0.20%
A:THR190.N-LIG308.O 3.39%
A:HIS41.NE2-LIG308.O 1.79%
A:GLN189.NE2-LIG308.O 3.19%
A:HIS172.NE2-LIG308.O8 1.59%
LIG308.N6-A:GLU166.OE2 1.59%
A:GLN189.NE2-LIG308.O 1.39%
LIG308.N6-A:GLU166.OE1 1.39%
LIG308.N6-B:SER1.OG 1.20%
A:GLN192.N-LIG308.N2 1.00%
B:SER1.OG-LIG308.O8 1.20%
LIG308.N-A:GLN192.O 0.60%
A:GLN192.N-LIG308.N2 0.80%
LIG308.N6-A:PHE140.O 0.40%
A:ASN142.ND2-LIG308.O8 0.60%
A:GLN192.N-LIG308.O1 0.20%
A:GLN192.N-LIG308.O1 0.40%
A:HIS41.NE2-LIG308.O 0.20%
LIG308.N-A:GLN192.O 0.40%
LIG308.N5-LIG308.O 0.20%
A:THR190.OG1-LIG308.O 0.20% LIG308.N5-LIG308.O 0.20% LIG308.N-LIG308.O 0.20% LIG308.N-LIG308.O8 0.20% LIG308.N5-LIG308.O8 0.20% A:GLN189.NE2-LIG308.O8 0.20% LIG308.N5-A:GLN189.OE1 0.20% LIG308.N-A:GLN189.O 0.20%
2.4 Concluding Remarks
129
Table 2.40 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-1-Mpro-N32hob model (denoted as “SARS-CoV-1-N3 dimer”) —the model has three sets of MD simulations [346] SARS-CoV-1-N3 rep1
rep2
rep3
B:ARG4.NH2-A:GLU290.OE2 45.82%
A:SER139.OG-B:GLN299.OE1 59.36%
B:SER139.OG-A:GLN299.OE1 42.83%
B:ARG4.NH1-A:GLU290.OE1 43.23%
B:SER139.OG-A:GLY2.O 32.27%
A:SER1.OG-B:GLU166.OE2 29.88%
B:SER1.OG-A:GLU166.OE2 30.68%
A:VAL125.N-B:ALA7.O 29.08%
A:ALA7.N-B:VAL125.O 28.88%
B:GLY11.N-A:GLU14.OE1 30.28%
B:ARG4.NH2-A:GLU290.OE2 28.69%
A:ARG4.NH1-B:LYS137.O 28.49%
B:SER1.OG-A:GLU166.OE1 29.28%
A:ALA7.N-B:VAL125.O 28.29%
B:ARG4.NH1-A:GLU290.OE2 28.29%
A:SER1.OG-B:GLU166.OE1 27.69%
B:GLY11.N-A:GLU14.OE1 27.69%
B:ARG4.NH2-A:GLU290.OE1 26.49%
A:GLY11.N-B:GLU14.OE1 25.30%
B:ARG4.NH1-A:GLU290.OE1 23.90%
B:VAL125.N-A:ALA7.O 25.10%
A:SER139.OG-B:GLN299.OE1 23.11%
A:SER1.OG-B:GLU166.OE1 23.51%
A:SER1.OG-B:GLU166.OE1 23.31%
A:GLY143.N-B:VAL303.O 22.11%
B:VAL125.N-A:ALA7.O 22.71%
A:GLY11.N-B:GLU14.OE1 21.71%
A:VAL125.N-B:ALA7.O 21.91%
B:SER1.OG-A:GLU166.OE1 22.11%
B:ALA7.N-A:VAL125.O 20.92%
A:SER1.OG-B:GLU166.OE2 21.12%
B:ALA7.N-A:VAL125.O 21.91%
A:VAL125.N-B:ALA7.O 20.92%
A:SER10.OG-A:GLU14.OE1 83.07%
A:SER10.OG-A:GLU14.OE1 82.47%
B:GLY11.N-A:GLU14.OE1 20.72% A:TYR209.OH-A:ILE259.O 64.34%
A:TYR209.OH-A:ILE259.O 67.53%
A:SER10.OG-A:GLU14.OE1 80.68%
A:TRP31.N-A:CYS16.O 64.14%
A:TRP31.N-A:CYS16.O 66.14%
A:GLU14.OE1-A:SER10.OG 80.68%
A:HIS163.N-A:SER147.O 62.95%
A:HIS163.N-A:SER147.O 65.14%
A:TYR209.OH-A:ILE259.O 66.73%
A:SER147.OG-A:SER144.O 60.76%
A:VAL114.N-A:TYR126.O 57.77%
A:THR201.OG1-A:GLU240.O 65.74%
A:THR257.OG1-A:LEU253.O 59.56%
A:ILE78.N-A:LYS90.O 57.77%
A:ILE78.N-A:LYS90.O 65.34%
A:THR201.OG1-A:GLU240.O 58.57%
A:THR257.OG1-A:LEU253.O 56.37%
A:HIS163.N-A:SER147.O 64.94%
A:VAL114.N-A:TYR126.O 57.57%
A:LEU87.N-A:CYS38.O 56.18%
A:THR135.OG1-A:ASN133.OD1 60.76%
A:ILE78.N-A:LYS90.O 57.37%
A:THR201.OG1-A:GLU240.O 54.38%
A:TRP31.N-A:CYS16.O 59.56%
A:LEU87.N-A:CYS38.O 56.18%
A:VAL157.N-A:LYS100.O 53.19%
A:VAL114.N-A:TYR126.O 57.17%
A:LEU115.N-A:VAL148.O 54.38%
A:LEU115.N-A:VAL148.O 52.39%
A:THR257.OG1-A:LEU253.O 55.18%
A:THR135.OG1-A:ASN133.OD1 53.59%
A:THR45.OG1-A:ASP48.OD1 51.00%
A:LEU167.N-A:VAL171.O 54.98%
A:ASN203.ND2-A:GLY109.O 53.39%
A:VAL36.N-A:LEU89.O 50.80%
A:VAL36.N-A:LEU89.O 54.58%
A:LYS5.NZ-A:GLU290.OE1 52.79%
A:SER147.OG-A:SER144.O 50.40%
A:SER123.N-A:ALA116.O 54.38%
A:ALA70.N-A:VAL73.O 52.59%
A:ASP153.N-A:CYS156.O 50.20%
A:TYR182.OH-A:CYS160.O 54.38%
A:LEU167.N-A:VAL171.O 52.39%
A:GLN19.N-A:GLN69.O 49.60%
A:LEU87.N-A:CYS38.O 53.98%
A:VAL36.N-A:LEU89.O 51.39%
A:LEU89.N-A:VAL36.O 49.00%
A:GLN299.NE2-A:ARG4.O 52.79%
A:LEU89.N-A:VAL36.O 51.20%
A:LEU27.N-A:VAL20.O 48.80%
A:LEU89.N-A:VAL36.O 52.19%
A:ASP153.N-A:CYS156.O 50.80%
A:LYS90.N-A:GLY79.O 48.01%
A:ILE136.N-A:HIS172.O 51.59%
A:LEU27.N-A:VAL20.O 50.40%
A:ARG88.N-A:SER81.O 48.01%
A:ASP153.N-A:CYS156.O 51.39%
A:VAL157.N-A:LYS100.O 50.40%
A:LEU167.N-A:VAL171.O 47.41%
A:VAL20.N-A:LEU27.O 51.00%
A:LYS90.N-A:GLY79.O 49.60%
A:VAL20.N-A:LEU27.O 47.21%
A:ARG131.N-A:THR135.O 50.60%
A:ARG131.N-A:THR135.O 49.60%
A:PHE8.N-A:SER113.OG 46.02%
A:GLY149.N-A:TYR161.O 50.20%
A:VAL18.N-A:GLY29.O 49.00%
A:ASN203.ND2-A:GLY109.O 45.82%
A:LEU115.N-A:VAL148.O 49.80%
A:TYR37.N-A:LEU30.O 48.61%
A:ALA173.N-A:MET165.O 45.82%
A:TYR37.N-A:LEU30.O 49.20%
A:ARG88.N-A:SER81.O 48.41%
A:ASN95.N-A:ASP33.O 45.42%
A:HIS172.N-A:ILE136.O 48.80%
A:GLN19.N-A:GLN69.O 46.41%
A:VAL18.N-A:GLY29.O 45.42%
A:THR25.OG1-A:CYS44.O 48.01%
A:SER123.N-A:ALA116.O 46.02%
A:TYR37.N-A:LEU30.O 45.42%
A:VAL157.N-A:LYS100.O 47.41%
A:GLY146.N-A:HIS163.O 45.82%
A:PHE112.N-A:CYS128.O 45.02%
A:PHE150.N-A:SER113.O 47.01%
A:PHE150.N-A:SER113.O 45.62%
A:ALA70.N-A:VAL73.O 43.82%
A:LEU242.N-A:ASN231.OD1 46.81%
A:LEU30.N-A:TYR37.O 45.22%
A:LEU75.N-A:VAL68.O 43.63%
A:ARG88.N-A:SER81.O 46.61%
A:ASN203.ND2-A:ASP289.O 44.82%
A:CYS128.N-A:PHE112.O 43.63%
A:ASN95.N-A:ASP33.O 46.61%
A:LEU75.N-A:VAL68.O 44.62%
A:TYR182.OH-A:CYS160.O 43.23%
A:LEU75.N-A:VAL68.O 46.41%
A:ALA173.N-A:MET165.O 43.82%
A:HIS172.N-A:ILE136.O 43.03%
A:ALA70.N-A:VAL73.O 46.41%
A:ASN95.N-A:ASP33.O 43.43%
A:LEU30.N-A:TYR37.O 42.23%
A:PHE8.N-A:SER113.OG 46.02%
A:LEU242.N-A:ASN231.OD1 43.43%
A:GLY146.N-A:HIS163.O 41.83%
A:LYS90.N-A:GLY79.O 46.02%
A:HIS172.N-A:ILE136.O 42.83%
A:PHE150.N-A:SER113.O 41.63%
A:GLN19.N-A:GLN69.O 45.42%
A:GLY109.N-A:MET130.O 42.83%
A:SER123.N-A:ALA116.O 41.24%
A:GLY146.N-A:HIS163.O 45.42%
A:CYS128.N-A:PHE112.O 42.23%
A:ASN231.N-A:LEU227.O 41.24%
A:ASN203.ND2-A:ASP289.O 44.42%
A:LEU32.N-A:THR35.O 41.63%
A:THR21.N-A:LEU67.O 41.24%
A:LEU32.N-A:THR35.O 44.42%
A:ASN95.ND2-A:TRP31.O 41.43%
A:LEU242.N-A:ASN231.OD1 41.04%
A:LEU27.N-A:VAL20.O 43.43%
A:ASN231.N-A:LEU227.O 41.24%
A:ASN214.ND2-A:ALA210.O 40.44%
A:ILE200.N-A:ASP289.OD2 43.43%
A:ASN133.ND2-A:GLY195.O 40.84%
A:LEU32.N-A:THR35.O 39.64%
A:LEU30.N-A:TYR37.O 43.43%
(continued)
130
2 3C-Like Protease (3CLpro)
Table 2.40 (continued) SARS-CoV-1-N3 rep1
rep2
rep3
A:TYR118.N-A:SER121.O 40.24%
A:LYS5.NZ-A:GLU290.OE1 38.45%
A:ARG105.NH2-A:PHE181.O 42.63%
A:ASN28.ND2-A:CYS145.O 39.04%
A:ALA234.N-A:PHE230.O 38.05%
A:ARG131.NH2-A:ASP289.OD2 42.43%
A:PHE8.N-A:SER113.OG 39.04%
A:ARG60.NH1-A:ASP48.OD1 37.85%
A:LEU205.N-A:THR201.O 41.83%
A:VAL20.N-A:LEU27.O 38.84%
A:ARG60.NH2-A:ASP48.OD2 37.65%
A:VAL18.N-A:GLY29.O 41.63%
A:THR199.N-A:ASN238.O 38.25%
A:ASN28.ND2-A:CYS145.O 37.45%
A:CYS22.N-A:THR25.O 41.63%
A:TYR182.OH-A:ILE106.O 38.05%
A:ASN203.ND2-A:ASP289.O 37.25%
A:CYS128.N-A:PHE112.O 41.63%
A:TYR239.N-A:ALA234.O 37.65%
A:THR135.OG1-A:ASN133.OD1 37.05%
A:ALA116.N-A:GLY124.O 40.84%
A:LEU268.N-A:MET264.O 36.85%
A:ARG105.NH2-A:PHE181.O 37.05%
A:THR111.OG1-A:ASP295.OD1 40.64%
A:THR45.OG1-A:ASP48.OD2 36.45%
A:GLN192.NE2-A:VAL186.O 37.05%
A:GLU14.N-A:SER10.O 40.24%
A:GLY149.N-A:TYR161.O 36.45%
A:ASN84.ND2-A:GLU178.O 36.85%
A:ASN214.ND2-A:ALA210.O 38.25%
A:THR21.N-A:LEU67.O 36.25%
A:GLY109.N-A:MET130.O 36.45%
A:THR21.N-A:LEU67.O 37.85%
A:GLN83.N-A:LEU86.O 36.25%
A:GLY149.N-A:TYR161.O 36.45%
A:PHE112.N-A:CYS128.O 37.65%
A:PHE112.N-A:CYS128.O 35.86%
A:ASN95.ND2-A:TRP31.O 35.46%
A:ASN231.N-A:LEU227.O 37.45%
A:SER144.OG-A:HIS163.NE2 35.86%
A:TYR118.N-A:SER121.O 34.66%
A:ASN95.ND2-A:TRP31.O 37.05%
A:ARG40.NH2-A:ASP187.OD1 35.66%
A:TYR182.N-A:GLY174.O 34.66%
A:THR199.N-A:ASN238.O 36.85%
A:SER113.OG-A:GLN127.OE1 35.26%
A:GLU14.N-A:SER10.O 34.06%
A:ASN28.ND2-A:CYS145.O 36.85%
A:ASN231.ND2-A:LEU242.O 35.06%
A:GLU290.N-A:GLU288.OE1 34.06%
A:LYS5.NZ-A:GLU290.OE2 36.85%
A:GLN189.N-A:MET49.O 32.47%
A:TYR239.N-A:ALA234.O 33.67%
A:ASN133.ND2-A:GLY195.O 36.65%
A:LEU205.N-A:THR201.O 31.87%
A:ILE281.N-A:SER284.O 33.47%
A:GLN192.NE2-A:VAL186.O 36.45%
A:CYS22.N-A:THR25.O 31.87%
A:SER113.OG-A:GLN127.OE1 33.47%
A:ILE281.N-A:SER284.O 36.06%
A:SER158.N-A:ASN151.O 31.08%
A:ARG40.NH2-A:ASP187.OD1 33.47%
A:SER147.OG-A:SER144.O 35.06%
A:GLU14.N-A:SER10.O 30.48%
A:ARG131.N-A:THR135.O 32.87%
A:ALA173.N-A:MET165.O 35.06%
A:GLN256.NE2-A:PRO252.O 29.88%
A:THR175.OG1-A:ASP176.O 31.87%
A:TYR182.N-A:GLY174.O 34.46%
A:VAL91.N-A:ASP34.O 29.68%
A:THR199.N-A:ASN238.O 31.67%
A:ASN203.ND2-A:GLY109.O 34.46%
Table 2.41 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-1-MproN3-2hob model (denoted as “SARS-CoV-1-N3 dimer”) —the model has three sets of MD simulations [346] (continuation-1) SARS-CoV-1-N3 rep1
rep2
rep3
A:THR45.OG1-A:ASP48.OD1 28.88%
A:LEU67.N-A:THR21.O 31.47%
A:GLY109.N-A:MET130.O 34.26%
A:GLN192.NE2-A:VAL186.O 28.69%
A:ASN231.ND2-A:LEU242.O 31.27%
A:SER113.OG-A:GLN127.OE1 33.47%
A:ARG40.NE-A:ASP187.OD2 28.49%
A:GLN189.N-A:MET49.O 30.48%
A:GLN83.N-A:LEU86.O 33.47%
A:SER81.N-A:ARG88.O 28.49%
A:GLN83.N-A:LEU86.O 30.28%
A:SER158.N-A:ASN151.O 32.67%
A:THR111.OG1-A:ASP295.OD2 28.29%
A:SER81.N-A:ARG88.O 30.28%
A:VAL91.N-A:ASP34.O 32.47%
A:ILE281.N-A:SER284.O 28.09%
A:THR292.OG1-A:ASP295.OD2 29.88%
A:LEU268.N-A:MET264.O 31.67%
A:THR198.OG1-A:GLU240.OE2 27.89%
A:SER1.OG-B:GLU166.OE2 29.88%
A:ASN84.ND2-A:GLU178.O 31.47%
A:LEU67.N-A:THR21.O 27.49%
A:GLY11.N-B:GLU14.OE1 29.88%
A:ALA255.N-A:GLY251.O 31.27%
A:THR111.OG1-A:ASP295.OD1 27.49%
A:CYS22.N-A:THR25.O 29.68%
A:THR175.OG1-A:ASP176.O 31.27%
A:GLN69.N-A:GLN19.O 27.09%
A:HIS80.ND1-A:ASN63.OD1 29.48%
A:SER81.N-A:ARG88.O 31.27%
A:ASN95.ND2-A:GLY15.O 27.09%
A:GLN69.N-A:GLN19.O 28.88%
A:TYR239.N-A:ALA234.O 31.08%
A:HIS80.ND1-A:ASN63.OD1 27.09%
A:VAL91.N-A:ASP34.O 28.88%
A:CYS160.N-A:GLY149.O 30.48%
A:ARG131.NH2-A:ASP289.OD2 26.89%
A:THR111.OG1-A:ASP295.OD2 28.88%
A:SER254.OG-A:ILE259.O 30.08%
A:ILE136.N-A:HIS172.O 26.29%
A:ARG40.NE-A:ASP187.OD2 28.69%
A:THR45.OG1-A:ASP48.OD1 29.28%
A:LYS102.N-A:VAL157.O 26.29%
A:ILE43.N-A:ARG40.O 28.69%
A:ARG40.NE-A:ASP187.OD2 29.08%
A:LEU208.N-A:VAL204.O 26.29%
A:SER144.OG-A:CYS117.O 28.69%
A:THR45.OG1-A:ASP48.OD2 28.88%
A:TYR182.N-A:GLY174.O 26.29%
A:LYS102.N-A:VAL157.O 28.49%
A:LYS102.N-A:VAL157.O 28.49%
A:GLN256.NE2-A:THR304.O 26.10%
A:THR225.OG1-A:ASP229.OD1 28.49%
A:ASN231.ND2-A:LEU242.O 28.49%
A:THR175.OG1-A:ASP176.O 25.90%
A:THR226.OG1-A:ASP229.OD2 27.69%
A:ASN28.ND2-A:GLY143.O 28.49%
A:TYR54.OH-A:ASP187.O 25.10%
A:SER144.OG-A:HIS163.NE2 27.49%
A:THR111.OG1-A:ASP295.OD2 28.29%
A:ILE43.N-A:ARG40.O 25.10%
A:SER158.N-A:ASN151.O 27.49%
A:TRP218.NE1-A:THR280.O 28.29%
A:GLY275.N-A:GLU270.O 25.10%
A:SER254.OG-A:ILE259.O 26.29%
A:CYS300.N-A:VAL296.O 28.09%
A:ARG105.NH2-A:PHE181.O 24.90%
A:THR198.OG1-A:GLU240.OE1 26.10%
A:ARG40.NH2-A:ASP187.OD1 28.09%
A:PHE159.N-A:LYS102.O 24.70%
A:SER113.N-A:PHE150.O 25.50%
A:SER144.OG-A:LEU141.O 26.89%
A:ALA7.N-B:VAL125.O 24.70%
A:THR98.OG1-A:ASN95.O 25.30%
A:LEU208.N-A:VAL204.O 26.10%
A:VAL104.N-A:PHE159.O 24.50%
A:LEU208.N-A:VAL204.O 24.70%
A:VAL104.N-A:PHE159.O 25.70%
(continued)
2.4 Concluding Remarks
131
Table 2.41 (continued) SARS-CoV-1-N3 rep1
rep2
rep3
A:THR198.OG1-A:GLU240.OE1 23.90%
A:LEU268.N-A:MET264.O 24.50%
A:GLN69.N-A:GLN19.O 25.50%
A:GLN19.NE2-A:ASN119.O 23.71%
A:VAL104.N-A:PHE159.O 24.30%
A:ASN151.N-A:SER158.O 25.50%
A:LYS269.N-A:CYS265.O 23.51%
A:LYS180.N-A:ASP176.OD1 23.71%
A:THR98.OG1-A:ASN95.O 25.30%
A:TYR182.OH-A:CYS160.O 23.51%
A:THR45.N-A:ASP48.OD1 23.71%
A:LEU67.N-A:THR21.O 24.30%
A:ASN274.N-A:GLU270.O 23.31%
A:TRP218.NE1-A:THR280.O 23.31%
A:ALA234.N-A:PHE230.O 23.90%
A:ASN151.N-A:SER158.O 23.31%
A:THR225.OG1-A:ASP229.OD2 23.31%
A:LEU272.N-A:LEU268.O 23.71%
A:GLN299.NE2-A:GLY2.O 23.11%
A:ALA255.N-A:GLY251.O 23.31%
A:ARG40.NE-A:ASP187.OD1 23.31%
A:LYS5.NZ-A:GLU288.OE2 22.91%
A:MET235.N-A:ASN231.O 23.31%
A:MET130.N-A:GLN110.O 23.11%
A:ARG131.NH1-A:ASP289.OD1 22.11%
A:GLN273.N-A:LYS269.O 23.11%
A:THR292.N-A:ASP295.OD1 22.91%
A:THR292.OG1-A:ASP295.OD1 21.71%
A:ASN95.ND2-A:GLY15.O 23.11%
A:THR198.OG1-A:GLU240.OE1 22.91%
A:THR292.OG1-A:ASP295.OD2 21.51%
A:THR111.OG1-A:ASP295.OD1 22.91%
A:GLN273.NE2-A:LYS269.O 22.91%
A:ASN84.ND2-A:GLU178.O 21.31%
A:THR198.OG1-A:GLU240.OE2 22.51%
A:THR21.OG1-A:THR26.OG1 22.51%
A:THR26.OG1-A:THR21.OG1 20.92%
A:GLN83.NE2-A:GLU178.O 22.31%
A:SER254.N-A:LEU250.O 22.11%
A:ALA255.N-A:GLY251.O 20.92%
A:THR292.OG1-A:ASP295.OD1 22.11%
A:SER284.N-A:ILE281.O 21.91%
A:ARG105.NH1-A:ASP176.OD1 20.72%
A:SER284.N-A:ILE281.O 21.51%
A:LYS269.N-A:CYS265.O 21.71%
A:MET162.N-A:THR175.O 20.52%
A:ARG105.NH1-A:ASP176.OD2 21.51%
A:ARG131.NH1-A:ASP289.OD1 21.71%
A:SER254.OG-A:ILE259.O 20.32%
A:ASN221.ND2-A:ALA266.O 21.51%
A:ARG40.NH2-A:ASP187.OD2 21.71%
A:CYS160.N-A:GLY149.O 20.12%
A:GLU240.N-A:THR199.O 21.51%
A:THR198.OG1-A:GLU240.OE2 21.51%
A:TYR182.OH-A:ILE106.O 21.31%
A:ARG105.NH1-A:ASP176.OD1 21.12%
B:SER10.OG-B:GLU14.OE1 84.06%
A:ALA116.N-A:GLY124.O 21.31%
A:ASN95.ND2-A:GLY15.O 21.12%
B:TYR182.OH-B:CYS160.O 70.72%
A:TYR101.OH-A:ASP33.OD2 21.12%
A:ARG105.NH1-A:LYS180.O 20.72%
B:TYR209.OH-B:ILE259.O 69.12%
A:LYS269.N-A:CYS265.O 20.92%
A:GLN107.N-A:GLN110.OE1 20.52%
B:THR201.OG1-B:GLU240.O 63.94%
A:GLN107.N-A:GLN110.OE1 20.92%
A:THR224.OG1-A:ASP263.OD2 20.52%
B:VAL114.N-B:TYR126.O 63.75%
A:ASN151.ND2-A:THR111.O 20.72%
A:TYR118.N-A:SER121.O 20.32%
B:TRP31.N-B:CYS16.O 62.15%
A:ILE136.N-A:HIS172.O 20.72%
A:ARG4.N-A:GLN299.OE1 20.32%
B:HIS163.N-B:SER147.O 61.35%
A:THR26.OG1-A:THR21.OG1 20.52%
A:SER113.N-A:PHE150.O 20.32%
B:ILE78.N-B:LYS90.O 59.36%
A:ARG40.NH2-A:ASP187.OD2 20.52%
B:TYR54.OH-B:ASP187.O 58.96%
A:ASN151.N-A:SER158.O 20.12%
B:SER10.OG-B:GLU14.OE1 85.66%
B:GLY146.N-B:HIS163.O 57.57%
A:GLY120.N-A:ASN28.OD1 20.12%
B:TYR209.OH-B:ILE259.O 76.69%
B:THR257.OG1-B:LEU253.O 55.78%
A:THR226.OG1-A:ASP229.OD1 20.12%
B:ILE78.N-B:LYS90.O 63.75%
B:LEU27.N-B:VAL20.O 54.78%
B:TYR54.OH-B:ASP187.O 62.35%
B:LEU87.N-B:CYS38.O 53.59%
B:SER10.OG-B:GLU14.OE1 84.86%
B:TRP31.N-B:CYS16.O 61.95%
B:VAL36.N-B:LEU89.O 53.19%
B:TYR54.OH-B:ASP187.O 68.33%
B:VAL36.N-B:LEU89.O 60.96%
B:LEU167.N-B:VAL171.O 52.19%
B:TYR209.OH-B:ILE259.O 66.53%
B:THR201.OG1-B:GLU240.O 60.16%
B:VAL157.N-B:LYS100.O 51.99%
B:THR201.OG1-B:GLU240.O 65.74%
B:LEU115.N-B:VAL148.O 59.36%
B:VAL20.N-B:LEU27.O 51.99%
B:ILE78.N-B:LYS90.O 64.14%
B:LEU27.N-B:VAL20.O 56.77%
B:GLY109.N-B:MET130.O 51.59%
B:TRP31.N-B:CYS16.O 63.15%
B:THR257.OG1-B:LEU253.O 55.58%
B:THR135.OG1-B:ASN133.OD1 51.39%
B:VAL36.N-B:LEU89.O 58.37%
B:LEU167.N-B:VAL171.O 55.18%
B:GLN19.N-B:GLN69.O 51.39%
B:VAL114.N-B:TYR126.O 56.77%
B:VAL114.N-B:TYR126.O 54.98%
B:GLN189.N-B:MET49.O 51.20%
B:GLY179.N-B:ASP176.OD1 55.38%
B:SER147.OG-B:SER144.O 52.99%
B:LEU115.N-B:VAL148.O 50.60%
B:LEU87.N-B:CYS38.O 53.78%
B:ASP153.N-B:CYS156.O 52.79%
B:LEU242.N-B:ASN231.OD1 49.20%
B:ALA173.N-B:MET165.O 53.78%
B:HIS172.N-B:ILE136.O 52.79%
B:ARG88.N-B:SER81.O 48.80%
B:THR135.OG1-B:ASN133.OD1 52.99%
B:GLY146.N-B:HIS163.O 52.19%
B:LYS90.N-B:GLY79.O 48.80%
B:THR257.OG1-B:LEU253.O 52.99%
B:ALA173.N-B:MET165.O 51.79%
B:ASP153.N-B:CYS156.O 48.41%
B:GLY109.N-B:MET130.O 52.59%
B:THR135.OG1-B:ASN133.OD1 51.39%
B:LEU89.N-B:VAL36.O 48.21%
B:HIS163.N-B:SER147.O 52.39%
B:ARG88.N-B:SER81.O 51.00%
B:ALA173.N-B:MET165.O 47.61%
B:VAL20.N-B:LEU27.O 52.19%
B:HIS163.N-B:SER147.O 50.60%
B:GLN192.NE2-B:VAL186.O 47.41%
B:LEU115.N-B:VAL148.O 51.59%
B:GLN19.N-B:GLN69.O 50.00%
B:ASN203.ND2-B:GLY109.O 46.81%
B:LEU167.N-B:VAL171.O 51.59%
B:TYR118.N-B:SER121.O 49.40%
B:CYS22.N-B:THR25.O 46.61%
B:GLN19.N-B:GLN69.O 50.20%
B:LEU87.N-B:CYS38.O 49.20%
B:PHE8.N-B:SER113.OG 46.61%
B:LEU89.N-B:VAL36.O 50.20%
B:CYS128.N-B:PHE112.O 49.20%
B:LEU75.N-B:VAL68.O 45.82%
B:ARG105.NH1-B:ASP176.OD2 49.60%
B:VAL157.N-B:LYS100.O 48.80%
B:SER123.N-B:ALA116.O 45.82%
B:LYS90.N-B:GLY79.O 49.00%
B:PHE150.N-B:SER113.O 48.80%
B:TYR37.N-B:LEU30.O 45.62%
B:TYR182.OH-B:ILE106.O 48.61%
B:SER123.N-B:ALA116.O 48.61%
132
2 3C-Like Protease (3CLpro)
Table 2.42 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-1-MproN3-2hob model (denoted as “SARS-CoV-1-N3 dimer”) —the model has three sets of MD simulations [346] (continuation-2) SARS-CoV-1-N3 rep1
rep2
rep3
B:GLN83.N-B:LEU86.O 43.63%
B:ASP153.N-B:CYS156.O 48.21%
B:LYS90.N-B:GLY79.O 48.01%
B:THR199.N-B:ASN238.O 43.63%
B:TYR37.N-B:LEU30.O 48.21%
B:VAL20.N-B:LEU27.O 47.41%
B:ASN231.N-B:LEU227.O 43.63%
B:VAL157.N-B:LYS100.O 48.21%
B:LEU89.N-B:VAL36.O 45.82%
B:ASN95.N-B:ASP33.O 43.03%
B:SER147.OG-B:SER144.O 47.81%
B:GLY149.N-B:TYR161.O 45.22%
B:GLY149.N-B:TYR161.O 43.03%
B:LEU27.N-B:VAL20.O 47.41%
B:LEU242.N-B:ASN231.OD1 44.82%
B:LEU30.N-B:TYR37.O 42.03%
B:SER123.N-B:ALA116.O 47.01%
B:TYR182.OH-B:CYS160.O 44.82%
B:ASN133.ND2-B:GLY195.O 41.04%
B:HIS172.N-B:ILE136.O 47.01%
B:ASN133.ND2-B:GLY195.O 44.22%
B:ALA70.N-B:VAL73.O 41.04%
B:LEU242.N-B:ASN231.OD1 46.81%
B:TYR37.N-B:LEU30.O 44.22%
B:TYR118.N-B:SER121.O 40.04%
B:LEU75.N-B:VAL68.O 46.41%
B:LEU32.N-B:THR35.O 43.23%
B:ARG131.N-B:THR135.O 39.84%
B:ALA70.N-B:VAL73.O 45.02%
B:VAL18.N-B:GLY29.O 43.23%
B:SER147.OG-B:SER144.O 39.84%
B:GLN299.NE2-B:ARG4.O 44.22%
B:ARG40.NH2-B:ASP187.OD1 42.83%
B:VAL18.N-B:GLY29.O 39.84%
B:PHE150.N-B:SER113.O 43.43%
B:THR292.OG1-B:ASP295.OD1 42.43%
B:LEU32.N-B:THR35.O 39.64%
B:SER144.OG-B:HIS163.NE2 43.23%
B:LEU30.N-B:TYR37.O 42.23%
B:ASN28.ND2-B:CYS145.O 39.64%
B:ARG88.N-B:SER81.O 42.83%
B:GLN192.NE2-B:VAL186.O 42.23%
B:PHE112.N-B:CYS128.O 39.24%
B:LEU30.N-B:TYR37.O 42.83%
B:ASN95.N-B:ASP33.O 42.23%
B:ASN95.ND2-B:TRP31.O 38.84%
B:GLY146.N-B:HIS163.O 42.63%
B:ASN28.ND2-B:CYS145.O 41.63%
B:ASN203.ND2-B:ASP289.O 38.25%
B:PHE8.N-B:SER113.OG 42.03%
B:LEU75.N-B:VAL68.O 41.63%
B:THR25.OG1-B:CYS44.O 38.05%
B:VAL18.N-B:GLY29.O 42.03%
B:ALA70.N-B:VAL73.O 41.24%
B:THR21.N-B:LEU67.O 38.05%
B:ASN95.N-B:ASP33.O 42.03%
B:PHE8.N-B:SER113.OG 41.04%
B:PHE150.N-B:SER113.O 37.85%
B:ARG40.NE-B:ASP187.OD2 41.83%
B:ARG40.NE-B:ASP187.OD2 40.64%
B:TYR182.N-B:GLY174.O 37.25%
B:GLN189.N-B:MET49.O 41.43%
B:ASN95.ND2-B:TRP31.O 40.64%
B:ARG40.NE-B:ASP187.OD2 37.05%
B:ASN95.ND2-B:TRP31.O 40.44%
B:ASN231.N-B:LEU227.O 40.04%
B:GLN299.NE2-B:ARG4.O 36.85%
B:ASN231.N-B:LEU227.O 40.04%
B:GLU14.N-B:SER10.O 39.04%
B:LEU205.N-B:THR201.O 35.26%
B:LYS180.N-B:ASP176.OD1 39.84%
B:THR21.N-B:LEU67.O 38.84%
B:TYR239.N-B:ALA234.O 34.26%
B:ASN203.ND2-B:ASP289.O 39.64%
B:ASN203.ND2-B:ASP289.O 38.25%
B:ARG131.NH2-B:ASP289.OD2 34.26%
B:ARG40.NH2-B:ASP187.OD1 39.24%
B:PHE112.N-B:CYS128.O 38.05%
B:SER113.OG-B:GLN127.OE1 34.26%
B:CYS128.N-B:PHE112.O 39.24%
B:THR199.N-B:ASN238.O 37.25%
B:ARG40.NH2-B:ASP187.OD1 34.06%
B:LEU32.N-B:THR35.O 39.04%
B:GLY109.N-B:MET130.O 36.85%
B:HIS172.N-B:ILE136.O 33.67%
B:PHE112.N-B:CYS128.O 38.25%
B:LEU205.N-B:THR201.O 36.85%
B:GLU14.N-B:SER10.O 33.07%
B:ILE200.N-B:ASP289.OD2 37.85%
B:ARG105.NH2-B:PHE181.O 36.65%
B:LYS102.N-B:VAL157.O 32.27%
B:GLN83.N-B:LEU86.O 37.05%
B:ILE281.N-B:SER284.O 36.45%
B:ASN231.ND2-B:LEU242.O 31.47%
B:ASN231.ND2-B:LEU242.O 36.65%
B:LEU57.N-B:ASN53.O 36.06%
B:HIS80.ND1-B:ASN63.OD1 31.08%
B:LEU57.N-B:ASN53.O 36.45%
B:TYR182.N-B:GLY174.O 35.26%
B:LEU268.N-B:MET264.O 30.68%
B:GLY149.N-B:TYR161.O 36.06%
B:THR45.OG1-B:ASP48.OD2 34.86%
B:TRP218.NE1-B:THR280.O 30.28%
B:THR199.N-B:ASN238.O 35.86%
B:LEU268.N-B:MET264.O 34.26%
B:ALA116.N-B:GLY124.O 30.08%
B:TYR118.N-B:SER121.O 35.66%
B:ARG131.N-B:THR135.O 33.47%
B:THR45.OG1-B:ASP48.OD2 30.08%
B:ILE281.N-B:SER284.O 35.06%
B:TYR239.N-B:ALA234.O 33.47%
B:ASN214.ND2-B:ALA210.O 29.28%
B:THR175.OG1-B:ASP176.O 34.86%
B:VAL91.N-B:ASP34.O 32.87%
B:ILE281.N-B:SER284.O 29.28%
B:THR45.OG1-B:ASP48.OD2 34.66%
B:CYS22.N-B:THR25.O 32.67%
B:THR175.OG1-B:ASP176.O 28.49%
B:ASN133.ND2-B:GLY195.O 34.46%
B:ASN231.ND2-B:LEU242.O 31.27%
B:VAL91.N-B:ASP34.O 28.49%
B:THR21.N-B:LEU67.O 34.26%
B:TRP218.NE1-B:THR280.O 31.08%
B:THR45.OG1-B:ASP48.OD1 27.69%
B:LEU205.N-B:THR201.O 33.67%
B:GLN189.N-B:MET49.O 30.28%
B:THR292.OG1-B:ASP295.OD2 27.49%
B:THR292.OG1-B:ASP295.OD1 33.07%
B:SER158.N-B:ASN151.O 30.28%
B:ARG131.NH1-B:ASP289.OD1 27.09%
B:THR25.OG1-B:CYS44.O 32.47%
B:THR25.OG1-B:CYS44.O 29.88%
B:SER158.N-B:ASN151.O 27.09%
B:THR175.N-B:MET162.O 32.27%
B:PHE305.N-B:GLN256.O 29.88%
B:HIS164.N-B:ALA173.O 26.69%
B:LEU268.N-B:MET264.O 31.87%
B:ASN203.ND2-B:GLY109.O 29.28%
B:GLN69.N-B:GLN19.O 26.49%
B:ARG131.N-B:THR135.O 31.67%
B:CYS160.N-B:GLY149.O 28.69%
B:THR198.OG1-B:GLU240.OE1 26.49%
B:TRP218.NE1-B:THR280.O 31.47%
B:GLN83.N-B:LEU86.O 28.49%
B:MET130.N-B:GLN110.O 26.29%
B:ASN28.ND2-B:CYS145.O 31.27%
B:LYS269.N-B:CYS265.O 28.49%
B:ASN151.ND2-B:THR111.O 26.10%
B:GLN192.NE2-B:VAL186.O 31.08%
B:THR175.OG1-B:ASP176.O 28.29%
B:SER254.OG-B:ILE259.O 25.90%
B:VAL91.N-B:ASP34.O 30.88%
B:LYS102.N-B:VAL157.O 28.29%
B:LEU208.N-B:VAL204.O 25.70%
B:TYR239.N-B:ALA234.O 30.28%
B:ILE200.N-B:ASP289.OD2 27.49%
B:THR111.OG1-B:ASP295.OD2 25.50%
B:SER158.N-B:ASN151.O 29.88%
B:SER144.OG-B:HIS163.NE2 27.49%
B:SER81.N-B:ARG88.O 25.30%
B:THR292.OG1-B:ASP295.OD2 29.08%
B:LEU67.N-B:THR21.O 27.09%
B:LEU67.N-B:THR21.O 25.10%
B:CYS22.N-B:THR25.O 28.88%
B:GLY120.N-B:ASN28.OD1 26.69%
B:VAL104.N-B:PHE159.O 24.50%
B:LYS102.N-B:VAL157.O 28.69%
B:GLN69.N-B:GLN19.O 26.69%
(continued)
2.4 Concluding Remarks
133
Table 2.42 (continued) SARS-CoV-1-N3 rep1
rep2
rep3
B:CYS128.N-B:PHE112.O 24.50%
B:LEU67.N-B:THR21.O 28.49%
B:GLN256.NE2-B:VAL303.O 26.29%
B:THR21.OG1-B:THR26.OG1 24.30%
B:SER254.N-B:LEU250.O 28.49%
B:HIS80.ND1-B:ASN63.OD1 26.10%
B:ALA234.N-B:PHE230.O 24.10%
B:MET130.N-B:GLN110.O 28.09%
B:THR292.OG1-B:ASP295.OD2 25.90%
B:TRP207.N-B:ASN203.O 23.90%
B:ALA116.N-B:GLY124.O 27.89%
B:TYR101.OH-B:ASP33.OD2 25.70%
B:LEU272.N-B:LEU268.O 23.90%
B:SER81.N-B:ARG88.O 27.89%
B:ASN95.ND2-B:GLY15.O 25.50%
B:SER113.N-B:PHE150.O 23.71%
B:GLN69.N-B:GLN19.O 27.69%
B:LYS180.N-B:ASP176.OD1 25.50%
B:SER144.OG-B:LEU141.O 23.51%
B:GLU14.N-B:SER10.O 27.69%
B:ILE136.N-B:HIS172.O 25.50%
B:GLN107.N-B:GLN110.OE1 23.11%
B:GLN107.N-B:GLN110.OE1 27.29%
B:ARG131.NH2-B:ASP289.OD2 24.70%
B:CYS160.N-B:GLY149.O 23.11%
B:HIS80.ND1-B:ASN63.OD1 27.29%
B:VAL104.N-B:PHE159.O 24.50%
B:LYS269.N-B:CYS265.O 22.91%
B:PHE159.N-B:LYS102.O 26.49%
B:SER81.N-B:ARG88.O 24.50%
B:THR111.OG1-B:ASP295.OD1 22.71%
B:ASN95.ND2-B:GLY15.O 26.49%
B:THR111.OG1-B:ASP295.OD1 23.71%
B:ASN151.N-B:SER158.O 22.51%
B:ASP216.N-B:ALA211.O 26.10%
B:GLN273.N-B:LYS269.O 23.51%
B:LEU86.N-B:GLN83.O 21.91%
B:VAL297.N-B:PRO293.O 26.10%
B:GLN19.NE2-B:ASN119.O 23.51%
B:TYR101.OH-B:ASP33.OD2 21.91%
B:THR98.OG1-B:ASN95.O 25.50%
B:SER113.N-B:PHE150.O 23.31%
B:ASP92.N-B:ARG76.O 21.71%
B:ASN203.ND2-B:GLY109.O 25.30%
B:THR98.OG1-B:ASN95.O 22.91%
B:THR98.OG1-B:ASN95.O 21.71%
B:ASN84.ND2-B:GLY179.O 25.30%
B:GLN107.N-B:GLN110.OE1 22.71%
B:LYS5.NZ-B:GLU288.OE2 21.51%
B:THR111.OG1-B:ASP295.OD1 25.10%
B:THR45.OG1-B:ASP48.OD1 22.11%
B:LYS5.NZ-B:GLU290.OE1 21.12%
B:MET162.N-B:THR175.O 24.30%
B:MET130.N-B:GLN110.O 21.91%
B:HIS41.NE2-B:HIS164.O 21.12%
B:ALA210.N-B:ALA206.O 24.30%
B:HIS164.N-B:ALA173.O 21.91%
B:SER254.N-B:LEU250.O 20.12%
B:VAL104.N-B:PHE159.O 24.10%
B:TYR209.N-B:LEU205.O 21.91%
B:SER113.N-B:PHE150.O 24.10%
B:ARG105.NH1-B:ASP176.OD1 21.71%
B:LYS269.N-B:CYS265.O 23.71%
B:ASP216.N-B:ALA211.O 21.51%
B:THR45.OG1-B:ASP48.OD1 23.71%
B:LEU86.N-B:GLN83.O 21.51%
B:THR111.OG1-B:ASP295.OD2 22.31%
B:ALA116.N-B:GLY124.O 21.51%
B:ALA255.N-B:GLY251.O 22.31%
B:THR26.OG1-B:THR21.OG1 21.31%
B:SER254.OG-B:ILE259.O 21.51%
B:ASN214.ND2-B:ALA210.O 21.31%
B:THR198.OG1-B:GLU240.OE1 21.12%
B:SER254.OG-B:ILE259.O 21.12%
B:ALA234.N-B:PHE230.O 20.92%
B:ARG105.NH1-B:ASP176.OD2 21.12%
B:TYR101.OH-B:ASP33.OD2 20.92%
B:LYS5.NZ-B:GLU290.OE1 21.12%
B:ILE136.N-B:HIS172.O 20.92%
B:LEU208.N-B:VAL204.O 21.12%
B:CYS160.N-B:GLY149.O 20.92%
B:CYS156.N-B:ASP153.O 20.92%
B:ASP176.N-B:LYS180.O 20.92%
B:ALA210.N-B:ALA206.O 20.72%
B:SER139.N-B:TYR126.OH 20.52%
B:LYS180.N-B:ASP176.OD2 20.72% B:GLN127.NE2-B:ASP295.OD2 20.52% B:TYR182.OH-B:ILE106.O 20.32% B:SER254.N-B:LEU250.O 20.32%
134
2 3C-Like Protease (3CLpro)
Table 2.43 The MD-HBs linking the ligands LIG307 and LIG308 of dimer the SARS-CoV-2Mpro-N3-6lu7 model (denoted as “SARS-CoV-2-N3 dimer”) —the model has three sets of MD simulations [346] SARS-CoV-2-N3 rep1
rep2
rep3
B:GLU166.N-LIG307.O 56.77%
B:GLU166.N-LIG307.O 56.18%
B:GLU166.N-LIG307.O 49.00%
LIG307.N-B:GLU166.O 38.05%
LIG307.N-B:GLU166.O 37.85%
LIG307.N-B:GLU166.O 38.65%
LIG307.N-B:GLN189.OE1 27.29%
LIG307.N5-B:HIS164.O 29.28%
LIG307.N5-B:HIS164.O 33.07%
LIG307.N5-B:HIS164.O 20.32%
LIG307.N-B:GLN189.OE1 24.90%
LIG307.N-B:GLN189.OE1 30.08%
B:HIS163.NE2-LIG307.O8 9.76%
B:HIS163.NE2-LIG307.O8 9.56%
B:HIS163.NE2-LIG307.O8 19.32%
B:CYS145.N-LIG307.O7 6.77%
B:CYS145.N-LIG307.O7 9.16%
LIG307.N-B:THR190.O 8.96%
LIG307.N-B:THR190.O 5.98%
LIG307.N-B:THR190.O 5.58%
B:CYS145.N-LIG307.O7 5.98%
B:GLN189.NE2-LIG307.O 3.98%
LIG307.N6-B:GLU166.OE1 1.59%
LIG307.N-B:GLN192.O 2.59%
LIG307.N-B:GLN192.O 2.39%
LIG307.N-B:GLN192.O 1.39%
B:GLN189.NE2-LIG307.O 1.59%
LIG307.N6-B:GLU166.OE1 1.00%
LIG307.N6-B:GLU166.OE2 1.39%
LIG307.N6-B:PHE140.O 1.59%
LIG307.N6-B:PHE140.O 0.80%
B:GLN192.N-LIG307.N2 1.20%
LIG307.N6-B:GLU166.OE2 1.00%
LIG307.N6-B:GLU166.OE2 0.80%
B:GLN189.NE2-LIG307.O 1.00%
B:THR190.N-LIG307.O 0.80%
B:THR190.N-LIG307.O 0.40%
LIG307.N6-B:PHE140.O 0.20%
LIG307.N6-B:GLU166.OE1 0.80%
B:THR26.N-LIG307.C5 0.40%
B:SER144.OG-LIG307.O8 0.20%
B:HIS41.NE2-LIG307.O 0.20%
B:GLN192.N-LIG307.N2 0.40%
B:GLN192.N-LIG307.O1 0.20%
B:SER144.OG-LIG307.O8 0.20% B:GLN192.N-LIG307.N2 0.20%
LIG308.N-A:GLU166.O 57.97%
LIG308.N-A:GLU166.O 49.00%
LIG308.N-LIG308.O8 42.23%
A:GLU166.N-LIG308.O 35.26%
LIG308.N-A:GLU166.O 29.68%
A:GLU166.N-LIG308.O 32.07%
LIG308.N-LIG308.O8 22.51%
A:GLU166.N-LIG308.O 21.91%
A:GLN189.NE2-LIG308.O 9.96%
LIG308.N-A:GLN189.OE1 8.37%
LIG308.N-A:GLN189.OE1 21.12%
LIG308.N-A:THR190.O 9.56%
LIG308.N-A:THR190.O 8.17%
A:GLN189.NE2-LIG308.O 7.17%
LIG308.N5-LIG308.O8 7.57%
LIG308.N5-LIG308.O8 6.57%
LIG308.N5-A:HIS164.O 6.57%
A:THR26.N-LIG308.O7 7.37%
A:GLN189.NE2-LIG308.O 5.98%
A:HIS41.NE2-LIG308.O 5.98%
LIG308.N-A:GLN189.OE1 1.39%
A:GLN189.NE2-LIG308.O8 4.78%
LIG308.N-A:GLN192.O 5.38%
A:ASN142.ND2-LIG308.O8 1.00%
LIG308.N5-A:GLN189.OE1 2.99%
A:GLN189.NE2-LIG308.O8 3.78%
LIG308.N6-A:GLN189.OE1 0.60%
A:THR26.N-LIG308.O7 2.59%
A:GLU166.N-LIG308.O42 3.19%
LIG308.N6-A:GLU166.OE2 0.40%
A:HIS41.NE2-LIG308.O 2.19%
LIG308.N6-A:LEU141.O 2.99%
A:GLN189.NE2-LIG308.O8 0.40%
LIG308.N6-A:GLN189.OE1 1.99%
A:CYS145.N-LIG308.O8 2.59%
A:HIS41.NE2-LIG308.O7 0.20%
A:SER144.N-LIG308.O8 1.79%
A:SER144.N-LIG308.O8 2.19%
LIG308.N5-A:HIS164.O 0.20%
A:SER46.OG-LIG308.O7 1.39%
LIG308.N6-A:SER144.OG 1.99%
LIG308.N-A:GLN192.O 0.20%
A:ASN142.ND2-LIG308.O8 1.39%
LIG308.N5-A:GLN189.OE1 1.59%
LIG308.N6-A:GLN189.NE2 0.20%
A:SER144.OG-LIG308.O8 0.60%
LIG308.N5-LIG308.O 1.20%
A:GLN189.NE2-LIG308.N6 0.20%
A:GLY143.N-LIG308.O8 0.60%
A:GLY143.N-LIG308.O8 1.20%
A:CYS145.N-LIG308.O8 0.60%
A:THR25.OG1-LIG308.O7 1.20%
LIG308.N6-A:SER46.OG 0.60%
LIG308.N-LIG308.O42 1.00%
LIG308.N-A:GLN192.O 0.40%
A:ASN142.ND2-LIG308.O7 0.60%
LIG308.N5-LIG308.O 0.40%
A:GLY143.N-LIG308.O7 0.60%
A:GLN189.NE2-LIG308.O7 0.40%
A:SER46.OG-LIG308.O8 0.40%
LIG308.N6-A:LEU141.O 0.40%
LIG308.N6-A:PHE140.O 0.20%
LIG308.N-A:GLN189.O 0.40%
A:HIS41.NE2-LIG308.C5 0.20%
A:CYS145.SG-LIG308.O 0.40%
A:GLN192.N-LIG308.N2 0.20%
A:HIS163.NE2-LIG308.O8 0.20%
A:ASN142.ND2-LIG308.O8 0.20%
A:GLN192.N-LIG308.N2 0.20%
A:GLU166.N-LIG308.O8 0.20%
LIG308.N6-A:ASN142.OD1 0.20%
A:GLN192.N-LIG308.O 0.20%
A:THR25.OG1-LIG308.O7 0.20%
A:GLN192.NE2-LIG308.O 0.20%
A:GLN189.NE2-LIG308.C4 0.20%
LIG308.N6-A:HIS41.O 0.20%
LIG308.N5-A:ASN142.OD1 0.20%
LIG308.N6-A:CYS44.O 0.20%
A:ASN142.ND2-LIG308.O7 0.20%
LIG308.N5-LIG308.O8 0.20%
A:ASN142.ND2-LIG308.O 0.20%
2.4 Concluding Remarks
135
Table 2.44 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-2-Mpro-N36lu7 model (denoted as “SARS-CoV-2-N3 dimer”) —the model has three sets of MD simulations [346] SARS-CoV-2-N3 rep1
rep2
rep3
A:SER139.OG-B:GLN299.OE1 57.57%
A:SER139.OG-B:GLN299.OE1 57.57%
A:SER139.OG-B:GLN299.OE1 58.37%
B:SER139.OG-A:GLN299.OE1 51.00%
B:SER139.OG-A:GLN299.OE1 53.19%
B:SER139.OG-A:GLN299.OE1 49.80%
B:VAL125.N-A:ALA7.O 32.67%
B:VAL125.N-A:ALA7.O 31.87%
B:GLY11.N-A:GLU14.OE1 33.47%
A:VAL125.N-B:ALA7.O 32.07%
B:SER1.OG-A:GLU166.OE1 31.67%
A:ALA7.N-B:VAL125.O 32.27%
B:SER1.OG-A:GLU166.OE2 30.68%
A:VAL125.N-B:ALA7.O 31.08%
A:GLY11.N-B:GLU14.OE1 30.68%
B:GLY11.N-A:GLU14.OE1 29.68%
B:GLY11.N-A:GLU14.OE1 28.88%
B:VAL125.N-A:ALA7.O 29.88%
A:GLY11.N-B:GLU14.OE1 29.28%
B:ARG4.NH1-A:GLU290.OE1 28.49%
B:SER1.OG-A:GLU166.OE2 24.30%
A:ALA7.N-B:VAL125.O 26.49%
A:ALA7.N-B:VAL125.O 27.69%
B:ALA7.N-A:VAL125.O 21.91%
A:SER1.OG-B:GLU166.OE2 26.29%
A:GLY11.N-B:GLU14.OE1 27.69%
B:SER1.OG-A:GLU166.OE1 21.71%
A:SER1.OG-B:GLU166.OE1 26.29%
B:ARG4.NH2-A:GLU290.OE2 25.90%
B:ARG4.NH2-A:GLU290.OE2 20.32%
B:ALA7.N-A:VAL125.O 26.10%
B:ALA7.N-A:VAL125.O 25.10%
B:ARG4.NH2-A:GLU290.OE1 20.12%
A:ARG4.NH2-B:GLU290.OE2 25.70%
B:SER1.OG-A:GLU166.OE2 22.11%
B:ARG4.NH1-A:GLU290.OE1 24.90%
A:ARG4.NH2-B:GLU290.OE2 21.12%
A:SER10.OG-A:GLU14.OE1 81.27%
B:SER1.OG-A:GLU166.OE1 23.31%
A:ARG4.NH1-B:GLU290.OE2 20.92%
A:SER267.OG-A:ASP263.O 69.12%
A:ARG4.NH1-B:GLU290.OE1 22.91%
A:ARG4.NH2-B:GLU290.OE1 20.32%
A:TRP31.N-A:CYS16.O 63.35%
B:ARG4.NH2-A:GLU290.OE2 22.71%
A:SER1.OG-B:GLU166.OE2 20.12%
A:SER10.OG-A:GLU14.OE1 83.27%
A:SER10.OG-A:GLU14.OE1 81.27%
A:TYR209.OH-A:ILE259.O 58.96%
A:TYR209.OH-A:ILE259.O 65.54%
A:SER267.OG-A:ASP263.O 68.53%
A:HIS163.N-A:SER147.O 58.76%
A:TRP31.N-A:CYS16.O 65.54%
A:TYR182.OH-A:CYS160.O 65.34%
A:VAL114.N-A:TYR126.O 58.76%
A:HIS163.N-A:SER147.O 64.14%
A:TRP31.N-A:CYS16.O 64.74%
A:THR201.OG1-A:GLU240.O 58.76%
A:LEU167.N-A:VAL171.O 62.95%
A:HIS163.N-A:SER147.O 62.95%
A:TYR54.OH-A:ASP187.O 58.57%
A:SER267.OG-A:ASP263.O 61.95%
A:THR201.OG1-A:GLU240.O 61.35%
A:SER144.OG-A:LEU141.O 57.77%
A:THR201.OG1-A:GLU240.O 61.55%
A:TYR209.OH-A:ILE259.O 61.16%
A:LEU87.N-A:CYS38.O 56.77%
A:VAL20.N-A:LEU27.O 61.16%
A:GLN299.NE2-A:ARG4.O 59.76%
A:VAL36.N-A:LEU89.O 52.39%
A:TYR182.OH-A:CYS160.O 60.76%
A:VAL20.N-A:LEU27.O 59.16%
A:PHE150.N-A:SER113.O 52.39%
A:ILE78.N-A:LYS90.O 60.56%
A:ILE78.N-A:LYS90.O 58.96%
A:GLY149.N-A:TYR161.O 52.19%
A:GLY146.N-A:HIS163.O 60.36%
A:GLY146.N-A:HIS163.O 57.97%
A:THR135.OG1-A:ASN133.OD1 51.99%
A:VAL114.N-A:TYR126.O 57.37%
A:LEU167.N-A:VAL171.O 56.77%
A:LYS88.N-A:SER81.O 51.79%
A:VAL36.N-A:LEU89.O 56.57%
A:VAL36.N-A:LEU89.O 56.18%
A:THR257.OG1-A:LEU253.O 51.20%
A:LEU27.N-A:VAL20.O 55.58%
A:THR45.OG1-A:ASP48.OD1 55.78%
A:ALA70.N-A:VAL73.O 51.00%
A:TYR54.OH-A:ASP187.O 55.58%
A:THR257.OG1-A:LEU253.O 55.18%
A:VAL20.N-A:LEU27.O 50.60%
A:GLY149.N-A:TYR161.O 54.18%
A:VAL114.N-A:TYR126.O 54.98%
A:THR175.OG1-A:ASP176.O 50.40%
A:LEU87.N-A:CYS38.O 53.98%
A:TYR37.N-A:LEU30.O 53.98%
A:LEU89.N-A:VAL36.O 50.20%
A:GLY109.N-A:MET130.O 53.19%
A:LEU89.N-A:VAL36.O 53.98%
A:GLY109.N-A:MET130.O 50.00%
A:SER147.OG-A:SER144.O 52.19%
A:GLY109.N-A:MET130.O 52.59%
A:GLY146.N-A:HIS163.O 48.61%
A:LYS88.N-A:SER81.O 51.79%
A:GLN256.NE2-A:VAL303.O 52.59%
A:ARG60.NH1-A:ASP48.OD2 48.21%
A:GLN19.N-A:GLN69.O 50.40%
A:GLY149.N-A:TYR161.O 51.79%
A:GLN256.NE2-A:VAL303.O 48.01%
A:TYR37.N-A:LEU30.O 50.20%
A:LEU27.N-A:VAL20.O 51.39%
A:SER123.N-A:ALA116.O 48.01%
A:THR135.OG1-A:ASN133.OD1 49.80%
A:LEU87.N-A:CYS38.O 51.20%
A:PHE8.N-A:SER113.OG 47.61%
A:GLN83.N-A:VAL86.O 49.80%
A:THR135.OG1-A:ASN133.OD1 50.40%
A:ASN95.N-A:ASP33.O 47.01%
A:LEU89.N-A:VAL36.O 49.80%
A:LYS88.N-A:SER81.O 49.60%
A:LEU167.N-A:VAL171.O 46.81%
A:SER144.OG-A:LEU141.O 49.60%
A:GLN192.NE2-A:VAL186.O 49.20%
A:VAL157.N-A:LYS100.O 46.41%
A:GLN299.NE2-A:ARG4.O 49.00%
A:ASP153.N-A:CYS156.O 47.61%
A:SER147.OG-A:SER144.O 46.41%
A:GLN192.NE2-A:VAL186.O 48.61%
A:THR175.OG1-A:ASP176.O 46.61%
A:LEU27.N-A:VAL20.O 46.41%
A:ASN95.N-A:ASP33.O 48.21%
A:ASN95.N-A:ASP33.O 46.22%
A:ASN203.ND2-A:ASP289.O 45.62%
A:THR257.OG1-A:LEU253.O 48.01%
A:GLN19.N-A:GLN69.O 46.02%
A:ARG131.N-A:THR135.O 45.22%
A:PHE150.N-A:SER113.O 47.41%
A:ASN203.ND2-A:ASP289.O 45.82%
A:VAL18.N-A:GLY29.O 45.22%
A:TYR182.N-A:GLY174.O 47.41%
A:SER123.N-A:ALA116.O 45.62%
A:GLN19.N-A:GLN69.O 45.02%
A:ALA70.N-A:VAL73.O 47.21%
A:LEU242.N-A:ASN231.OD1 45.42%
A:TYR37.N-A:LEU30.O 45.02%
A:SER123.N-A:ALA116.O 47.21%
A:ALA70.N-A:VAL73.O 45.22%
A:LYS90.N-A:GLY79.O 44.22%
A:ASN203.ND2-A:ASP289.O 46.61%
A:LEU30.N-A:TYR37.O 44.62%
A:HIS172.N-A:ILE136.O 44.02%
A:THR175.OG1-A:ASP176.O 46.02%
A:TYR182.N-A:GLY174.O 43.82%
A:ILE281.N-A:SER284.O 43.63%
A:ILE281.N-A:SER284.O 44.22%
A:SER144.OG-A:LEU141.O 43.63%
A:MET130.N-A:GLN110.O 43.23%
A:VAL18.N-A:GLY29.O 44.22%
A:SER147.OG-A:SER144.O 43.63%
A:LEU30.N-A:TYR37.O 42.83%
A:TYR182.OH-A:CYS160.O 60.56% A:ILE78.N-A:LYS90.O 60.16%
(continued)
136
2 3C-Like Protease (3CLpro)
Table 2.44 (continued) SARS-CoV-2-N3 rep1
rep2
rep3
A:CYS22.N-A:THR25.O 43.43%
A:VAL157.N-A:LYS100.O 43.43%
A:VAL91.N-A:ASP34.O 42.63%
A:LEU115.N-A:VAL148.O 42.63%
A:PHE150.N-A:SER113.O 42.83%
A:THR45.OG1-A:ASP48.OD2 42.03%
A:THR25.OG1-A:CYS44.O 42.63%
A:ASN231.N-A:LEU227.O 42.63%
A:ASN95.ND2-A:TRP31.O 41.63%
A:THR45.OG1-A:ASP48.OD1 42.23%
A:LEU75.N-A:VAL68.O 41.63%
A:LEU75.N-A:VAL68.O 41.24%
A:ASP153.N-A:CYS156.O 41.43%
A:ILE281.N-A:SER284.O 41.43%
A:ARG60.NH2-A:ASP48.OD1 41.24%
A:LEU75.N-A:VAL68.O 41.24%
A:PHE8.N-A:SER113.OG 41.43%
A:ASN133.ND2-A:GLY195.O 40.24%
A:LYS90.N-A:GLY79.O 40.24%
A:ASN95.ND2-A:TRP31.O 41.43%
A:GLN83.N-A:VAL86.O 39.64%
A:PHE8.N-A:SER113.OG 40.04%
A:VAL18.N-A:GLY29.O 40.44%
A:LEU32.N-A:VAL35.O 39.04%
A:VAL157.N-A:LYS100.O 40.04%
A:ARG105.NH2-A:PHE181.O 40.44%
A:THR199.N-A:ASN238.O 39.04%
A:LEU205.N-A:THR201.O 39.84%
A:GLN83.N-A:VAL86.O 40.44%
A:GLN299.NE2-A:ARG4.O 38.65%
A:VAL91.N-A:ASP34.O 39.04%
A:LEU205.N-A:THR201.O 40.44%
A:ASP153.N-A:CYS156.O 38.65%
A:LEU30.N-A:TYR37.O 38.65%
A:LYS90.N-A:GLY79.O 39.64%
A:ALA173.N-A:MET165.O 38.45%
A:LEU242.N-A:ASN231.OD1 38.25%
A:VAL91.N-A:ASP34.O 39.24%
A:HIS80.ND1-A:ASN63.OD1 38.45%
A:ASN231.N-A:LEU227.O 38.05%
A:HIS172.N-A:ILE136.O 38.45%
A:TYR182.N-A:GLY174.O 38.25%
A:TYR239.N-A:ALA234.O 37.45%
A:PHE112.N-A:CYS128.O 38.05%
A:ASN28.ND2-A:CYS145.O 38.05%
A:PHE112.N-A:CYS128.O 37.45%
A:ASN214.ND2-A:ALA210.O 37.85%
A:LEU205.N-A:THR201.O 37.85%
A:LEU32.N-A:VAL35.O 37.05%
A:GLU14.N-A:SER10.O 37.45%
A:SER301.OG-A:VAL297.O 37.45%
A:ARG105.NH2-A:PHE181.O 36.85%
A:TYR239.N-A:ALA234.O 37.45%
A:CYS300.N-A:VAL296.O 37.05%
A:ARG40.NE-A:ASP187.OD2 36.85%
A:LEU32.N-A:VAL35.O 37.45%
A:THR111.OG1-A:ASP295.OD1 36.85%
A:HIS172.N-A:ILE136.O 36.85%
A:CYS22.N-A:THR25.O 36.85%
A:SER254.OG-A:ILE259.O 35.86%
A:ASN133.ND2-A:GLY195.O 36.45%
A:SER301.OG-A:VAL297.O 36.25%
A:SER113.N-A:PHE150.O 35.86%
A:THR199.N-A:ASN238.O 36.45%
A:TYR118.N-A:SER121.O 35.06%
A:SER158.N-A:ASN151.O 35.66%
A:SER158.N-A:ASN151.O 36.06%
A:ILE136.N-A:HIS172.O 34.86%
A:ASN151.ND2-A:THR111.O 35.46%
A:ASN95.ND2-A:TRP31.O 35.86%
A:ILE200.N-A:ASP289.OD1 34.86%
A:GLU14.N-A:SER10.O 35.06%
Table 2.45 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-2-Mpro-N36lu7 model (denoted as “SARS-CoV-2-N3 dimer”) —the model has three sets of MD simulations [346] (continuation-1) SARS-CoV-2-N3 rep1
rep2
rep3
A:ARG40.NH2-A:ASP187.OD1 35.66%
A:THR199.N-A:ASN238.O 34.66%
A:TYR118.N-A:SER121.O 34.06%
A:ALA173.N-A:MET165.O 35.46%
A:ASN133.ND2-A:GLY195.O 34.66%
A:ASN84.ND2-A:GLU178.O 33.86%
A:SER254.OG-A:ILE259.O 35.26%
A:SER254.OG-A:ILE259.O 34.26%
A:ARG105.NH2-A:PHE181.O 33.07%
A:ASN214.ND2-A:ALA210.O 34.26%
A:ALA173.N-A:MET165.O 34.26%
A:LYS269.N-A:CYS265.O 32.87%
A:ALA116.N-A:GLY124.O 34.26%
A:LEU115.N-A:VAL148.O 34.06%
A:LEU115.N-A:VAL148.O 32.67%
A:ILE136.N-A:HIS172.O 33.86%
A:SER113.N-A:PHE150.O 33.47%
A:LEU67.N-A:THR21.O 31.47%
A:THR111.OG1-A:ASP295.OD2 33.07%
A:SER158.N-A:ASN151.O 33.27%
A:TYR239.N-A:ALA234.O 31.08%
A:THR21.N-A:LEU67.O 32.67%
A:THR111.OG1-A:ASP295.OD1 33.27%
A:ASN214.ND2-A:ALA210.O 31.08%
A:SER113.N-A:PHE150.O 32.47%
A:ASN203.ND2-A:GLY109.O 32.67%
A:LEU242.N-A:ASN231.OD1 30.88%
A:MET130.N-A:GLN110.O 31.67%
A:ALA116.N-A:GLY124.O 32.67%
A:THR292.OG1-A:ASP295.OD1 30.88%
A:HIS41.NE2-A:HIS164.O 30.68%
A:ASN151.ND2-A:THR111.O 32.47%
A:LEU268.N-A:MET264.O 30.48%
A:TYR118.N-A:SER121.O 30.48%
A:GLN189.N-A:MET49.O 32.47%
A:THR111.OG1-A:ASP295.OD2 30.28%
A:ASN151.ND2-A:THR111.O 30.28%
A:THR111.OG1-A:ASP295.OD2 32.27%
A:THR243.OG1-A:HIS246.ND1 29.88%
A:LEU67.N-A:THR21.O 30.28%
A:ASN231.ND2-A:LEU242.O 32.07%
A:THR21.N-A:LEU67.O 28.88%
A:TRP218.NE1-A:THR280.O 30.08%
A:THR292.OG1-A:ASP295.OD2 31.87%
A:ALA116.N-A:GLY124.O 28.88%
A:THR111.OG1-A:ASP295.OD1 29.68%
A:HIS80.ND1-A:ASN63.OD1 31.67%
A:VAL125.N-B:ALA7.O 28.69%
A:ASN203.ND2-A:GLY109.O 29.48%
A:THR21.N-A:LEU67.O 31.27%
A:GLN192.NE2-A:VAL186.O 28.29%
A:GLN107.N-A:GLN110.OE1 29.48%
A:ARG60.NH1-A:ASP48.OD1 30.68%
A:VAL86.N-A:GLN83.O 27.09%
A:LYS269.N-A:CYS265.O 29.08%
A:ARG60.NH2-A:ASP48.OD2 30.68%
A:GLN69.N-A:GLN19.O 26.89%
A:CYS128.N-A:PHE112.O 28.49%
A:ARG40.NE-A:ASP187.OD2 28.88%
A:THR292.OG1-A:ASP295.OD2 26.89%
A:ARG40.NH2-A:ASP187.OD2 28.49%
A:LEU67.N-A:THR21.O 28.69%
A:ALA234.N-A:PHE230.O 26.69%
A:ILE200.N-A:ASP289.OD2 28.29%
A:LEU268.N-A:MET264.O 28.49%
A:CYS128.N-A:PHE112.O 26.29%
A:LEU208.N-A:VAL204.O 28.29%
A:SER1.OG-B:GLU166.OE1 28.29%
A:ILE136.N-A:HIS172.O 26.10%
A:THR21.OG1-A:THR26.OG1 27.89%
A:CYS300.N-A:VAL296.O 28.09%
A:SER81.N-A:LYS88.O 26.10%
A:VAL86.N-A:GLN83.O 27.69%
A:MET130.N-A:GLN110.O 28.09%
A:PHE159.N-A:LYS102.O 25.50%
A:HIS80.ND1-A:ASN63.OD1 27.69%
A:ARG40.NH2-A:ASP187.OD1 27.69%
A:ALA255.N-A:GLY251.O 25.30%
A:THR292.OG1-A:ASP295.OD1 27.09%
A:LYS5.NZ-A:GLU290.OE1 27.49%
A:ASN231.N-A:LEU227.O 25.30%
(continued)
2.4 Concluding Remarks
137
Table 2.45 (continued) SARS-CoV-2-N3 rep1
rep2
rep3
A:GLU14.N-A:SER10.O 26.89%
A:ARG131.N-A:THR135.O 27.29%
A:ASN180.N-A:ASP176.OD2 25.10%
A:LEU268.N-A:MET264.O 26.89%
A:ALA255.N-A:GLY251.O 26.89%
A:LEU208.N-A:VAL204.O 24.90%
A:LYS102.N-A:VAL157.O 26.69%
A:ARG40.NH2-A:ASP187.OD2 26.89%
A:ASN95.ND2-A:GLY15.O 24.90%
A:THR292.OG1-A:ASP295.OD2 25.50%
A:VAL86.N-A:GLN83.O 26.69%
A:VAL104.N-A:PHE159.O 24.70%
A:ASN274.ND2-A:GLU270.O 25.50%
A:ASN84.ND2-A:GLU178.O 26.49%
A:ARG4.NE-A:PHE3.O 24.30%
A:THR198.OG1-A:GLU240.OE2 24.90%
A:PHE159.N-A:LYS102.O 26.49%
A:ASN203.ND2-A:GLY109.O 23.71%
A:ASN221.N-A:SER267.OG 24.90%
A:SER62.N-A:ASN65.OD1 26.49%
A:THR98.OG1-A:ASN95.O 23.31%
A:THR243.OG1-A:HIS246.ND1 24.50%
A:GLN107.N-A:GLN110.OE1 26.10%
A:PHE112.N-A:CYS128.O 22.91%
A:ASN95.ND2-A:GLY15.O 24.50%
A:ASN274.ND2-A:GLU270.O 24.90%
A:LYS102.N-A:VAL157.O 22.71%
A:VAL186.N-A:GLN192.OE1 24.50%
A:VAL104.N-A:PHE159.O 24.90%
A:ASN221.N-A:SER267.OG 22.71%
A:PHE159.N-A:LYS102.O 24.30%
A:ASN28.ND2-A:CYS145.O 24.90%
A:GLY120.N-A:ASN28.OD1 22.51%
A:SER62.N-A:ASN65.OD1 24.30%
A:LYS102.N-A:VAL157.O 24.70%
A:TRP218.NE1-A:THR280.O 21.91%
A:VAL104.N-A:PHE159.O 24.10%
A:CYS128.N-A:PHE112.O 24.50%
A:SER284.N-A:ILE281.O 21.71%
A:GLN189.N-A:MET49.O 23.51%
A:THR98.OG1-A:ASN95.O 24.30%
A:GLN107.N-A:GLN110.OE1 21.51%
A:SER81.N-A:LYS88.O 22.91%
A:GLN69.N-A:GLN19.O 24.10%
A:ILE200.N-A:ASP289.OD2 21.31%
A:LYS5.NZ-A:GLU290.OE1 22.91%
A:THR243.OG1-A:HIS246.ND1 23.90%
A:ILE200.N-A:ASP289.OD1 21.31%
A:ALA255.N-A:GLY251.O 22.71%
A:TRP218.NE1-A:THR280.O 23.71%
A:CYS22.N-A:THR25.O 21.12%
A:ASN28.ND2-A:CYS145.O 21.91%
A:ARG131.NH2-A:ASP289.OD1 23.71%
A:THR198.OG1-A:GLU240.OE1 21.12%
A:THR198.OG1-A:GLU240.OE1 21.91%
A:LEU208.N-A:VAL204.O 23.31%
A:ARG4.N-A:GLN299.OE1 21.12%
A:ARG40.NE-A:ASP187.OD1 21.91%
A:ARG40.NE-A:ASP187.OD1 23.31%
A:SER139.N-A:TYR126.OH 21.12%
A:ASN231.ND2-A:LEU242.O 21.71%
A:ARG4.N-A:GLN299.OE1 22.91%
A:GLN273.N-A:LYS269.O 20.92%
A:THR45.OG1-A:ASP48.OD2 21.71%
A:LYS269.N-A:CYS265.O 22.91%
A:CYS38.N-A:LEU87.O 20.52%
A:ASN180.N-A:ASP176.OD1 21.12%
A:ALA234.N-A:PHE230.O 22.91%
A:THR98.OG1-A:ASN95.O 21.12%
A:THR21.OG1-A:THR26.OG1 22.91%
B:SER10.OG-B:GLU14.OE1 85.86%
A:GLY120.N-A:ASN28.OD1 20.92%
A:ASN95.ND2-A:GLY15.O 22.71%
B:SER267.OG-B:ASP263.O 67.33%
A:ARG131.N-A:THR135.O 20.72%
A:THR292.OG1-A:ASP295.OD1 22.71%
B:THR201.OG1-B:GLU240.O 61.75%
A:THR292.N-A:ASP295.OD2 20.72%
A:ASN221.N-A:SER267.OG 22.31%
B:TYR209.OH-B:ILE259.O 61.75%
A:ARG105.NH1-A:ASP176.OD2 20.72%
A:ASN151.N-A:SER158.O 22.11%
B:TRP31.N-B:CYS16.O 61.55%
A:ARG4.N-A:GLN299.OE1 20.52%
A:THR198.OG1-A:GLU240.OE2 22.11%
B:TYR182.OH-B:CYS160.O 59.96%
A:ARG131.NH2-A:ASP289.OD2 20.52%
A:SER81.N-A:LYS88.O 22.11%
B:ILE78.N-B:LYS90.O 59.36%
A:SER139.N-A:TYR126.OH 20.52%
A:HIS41.NE2-A:HIS164.O 21.71%
B:LEU87.N-B:CYS38.O 56.18%
A:LEU272.N-A:LEU268.O 20.32%
A:TYR54.OH-A:ASP187.O 20.72%
B:GLN299.NE2-B:ARG4.O 55.98%
A:GLN69.N-A:GLN19.O 20.12%
A:THR292.N-A:ASP295.OD1 20.52%
B:LEU167.N-B:VAL171.O 55.98%
A:CYS38.N-A:LEU87.O 20.32%
B:GLY109.N-B:MET130.O 55.18%
B:SER10.OG-B:GLU14.OE1 83.86%
B:VAL20.N-B:LEU27.O 54.18%
B:HIS163.N-B:SER147.O 63.94%
B:SER10.OG-B:GLU14.OE1 84.86%
B:VAL114.N-B:TYR126.O 52.59%
B:TRP31.N-B:CYS16.O 63.35%
B:SER267.OG-B:ASP263.O 65.94%
B:SER144.OG-B:LEU141.O 51.79%
B:THR201.OG1-B:GLU240.O 61.95%
B:TRP31.N-B:CYS16.O 65.14%
B:HIS163.N-B:SER147.O 51.59%
B:TYR182.OH-B:CYS160.O 61.95%
B:THR201.OG1-B:GLU240.O 62.35%
B:LYS88.N-B:SER81.O 51.39%
B:SER267.OG-B:ASP263.O 60.76%
B:ARG40.NH2-B:ASP187.OD1 59.96%
B:LEU89.N-B:VAL36.O 51.39%
B:TYR209.OH-B:ILE259.O 58.76%
B:HIS163.N-B:SER147.O 59.36%
B:VAL36.N-B:LEU89.O 50.60%
B:VAL114.N-B:TYR126.O 58.57%
B:VAL114.N-B:TYR126.O 59.36%
B:SER123.N-B:ALA116.O 50.20%
B:ILE78.N-B:LYS90.O 58.17%
B:ILE78.N-B:LYS90.O 58.96%
B:GLN192.NE2-B:VAL186.O 50.20%
B:LEU87.N-B:CYS38.O 57.37%
B:TYR209.OH-B:ILE259.O 58.96%
B:GLN19.N-B:GLN69.O 49.80%
B:GLN299.NE2-B:ARG4.O 57.17%
B:LEU167.N-B:VAL171.O 57.97%
B:LEU115.N-B:VAL148.O 49.40%
B:THR257.OG1-B:LEU253.O 56.57%
B:LEU87.N-B:CYS38.O 57.77%
B:GLY149.N-B:TYR161.O 49.00%
B:VAL36.N-B:LEU89.O 55.18%
B:TYR182.OH-B:CYS160.O 56.37%
B:LEU27.N-B:VAL20.O 48.61%
B:LEU167.N-B:VAL171.O 54.98%
B:LYS88.N-B:SER81.O 54.18%
B:GLN189.N-B:MET49.O 48.41%
B:GLY109.N-B:MET130.O 54.98%
B:HIS172.N-B:ILE136.O 52.99%
B:VAL91.N-B:ASP34.O 47.81%
B:LYS88.N-B:SER81.O 53.39%
B:THR257.OG1-B:LEU253.O 52.99%
B:GLY146.N-B:HIS163.O 47.81%
B:SER144.OG-B:LEU141.O 51.59%
B:ARG40.NE-B:ASP187.OD2 51.99%
B:THR45.OG1-B:ASP48.OD2 47.81%
B:SER147.OG-B:SER144.O 50.60%
B:SER144.OG-B:LEU141.O 51.99%
B:THR257.OG1-B:LEU253.O 47.61%
B:TYR37.N-B:LEU30.O 50.40%
B:GLN299.NE2-B:ARG4.O 51.59%
B:ASN95.N-B:ASP33.O 46.61%
138
2 3C-Like Protease (3CLpro)
Table 2.46 The MD-HBs (with occupancy rates ≥20%) of dimer the SARS-CoV-2-Mpro-N36lu7 model (denoted as “SARS-CoV-2-N3 dimer”) —the model has three sets of MD simulations [346] (continuation-2) SARS-CoV-2-N3 rep1
rep2
rep3
B:GLY149.N-B:TYR161.O 50.20%
B:VAL36.N-B:LEU89.O 50.60%
B:TYR37.N-B:LEU30.O 45.82%
B:LEU89.N-B:VAL36.O 49.20%
B:THR135.OG1-B:ASN133.OD1 50.20%
B:LEU75.N-B:VAL68.O 45.82%
B:LEU115.N-B:VAL148.O 47.81%
B:GLN83.N-B:VAL86.O 50.20%
B:GLN83.N-B:VAL86.O 44.62%
B:LEU75.N-B:VAL68.O 47.61%
B:LEU89.N-B:VAL36.O 50.00%
B:VAL18.N-B:GLY29.O 44.62%
B:PHE150.N-B:SER113.O 46.41%
B:GLY149.N-B:TYR161.O 50.00%
B:ALA70.N-B:VAL73.O 44.22%
B:VAL18.N-B:GLY29.O 46.41%
B:GLN192.NE2-B:VAL186.O 49.60%
B:ASN203.ND2-B:ASP289.O 44.02%
B:ASN203.ND2-B:ASP289.O 46.22%
B:VAL20.N-B:LEU27.O 49.40%
B:PHE8.N-B:SER113.OG 44.02%
B:SER123.N-B:ALA116.O 46.02%
B:LEU27.N-B:VAL20.O 48.61%
B:ASN95.ND2-B:TRP31.O 43.63%
B:GLY146.N-B:HIS163.O 46.02%
B:TYR37.N-B:LEU30.O 48.61%
B:PHE150.N-B:SER113.O 43.43%
B:ASN95.N-B:ASP33.O 46.02%
B:SER147.OG-B:SER144.O 48.01%
B:SER147.OG-B:SER144.O 43.43%
B:ALA70.N-B:VAL73.O 45.82%
B:GLY146.N-B:HIS163.O 48.01%
B:ARG105.NH2-B:PHE181.O 43.23%
B:ALA173.N-B:MET165.O 45.62%
B:LEU115.N-B:VAL148.O 47.81%
B:VAL157.N-B:LYS100.O 43.03%
B:HIS172.N-B:ILE136.O 45.22%
B:GLY109.N-B:MET130.O 47.61%
B:LEU32.N-B:VAL35.O 42.03%
B:GLN19.N-B:GLN69.O 45.02%
B:ALA70.N-B:VAL73.O 47.01%
B:THR111.OG1-B:ASP295.OD1 42.03%
B:PHE8.N-B:SER113.OG 44.62%
B:ARG131.N-B:THR135.O 46.41%
B:LYS90.N-B:GLY79.O 41.83%
B:GLN83.N-B:VAL86.O 44.22%
B:PHE150.N-B:SER113.O 46.22%
B:ILE136.N-B:HIS172.O 41.63%
B:VAL20.N-B:LEU27.O 43.23%
B:LEU242.N-B:ASN231.OD1 44.62%
B:LEU205.N-B:THR201.O 41.63%
B:LEU27.N-B:VAL20.O 42.83%
B:ASN203.ND2-B:ASP289.O 44.62%
B:TYR182.N-B:GLY174.O 41.43%
B:GLN192.NE2-B:VAL186.O 42.23%
B:GLN19.N-B:GLN69.O 44.42%
B:GLU14.N-B:SER10.O 40.84%
B:LYS90.N-B:GLY79.O 41.63%
B:VAL157.N-B:LYS100.O 44.22%
B:ILE281.N-B:SER284.O 40.64%
B:LEU242.N-B:ASN231.OD1 41.43%
B:LEU32.N-B:VAL35.O 44.02%
B:LYS5.NZ-B:GLU290.OE2 40.24%
B:ASN28.ND2-B:CYS145.O 41.43%
B:SER123.N-B:ALA116.O 44.02%
B:SER158.N-B:ASN151.O 39.64%
B:TYR182.N-B:GLY174.O 41.24%
B:VAL18.N-B:GLY29.O 43.63%
B:ARG60.NH1-B:ASP48.OD2 39.24%
B:VAL157.N-B:LYS100.O 41.24%
B:LYS90.N-B:GLY79.O 43.63%
B:LEU30.N-B:TYR37.O 38.65%
B:ILE281.N-B:SER284.O 41.04%
B:ASN95.N-B:ASP33.O 43.43%
B:TYR239.N-B:ALA234.O 38.45%
B:LEU30.N-B:TYR37.O 40.64%
B:GLN189.N-B:MET49.O 43.23%
B:THR199.N-B:ASN238.O 38.25%
B:TYR118.N-B:SER121.O 40.64%
B:LEU75.N-B:VAL68.O 43.23%
B:LEU242.N-B:ASN231.OD1 37.05%
B:THR199.N-B:ASN238.O 40.24%
B:VAL91.N-B:ASP34.O 42.63%
B:ASN214.ND2-B:ALA210.O 37.05%
B:VAL91.N-B:ASP34.O 40.24%
B:PHE8.N-B:SER113.OG 41.83%
B:HIS172.N-B:ILE136.O 36.85%
B:TYR239.N-B:ALA234.O 40.24%
B:TYR182.N-B:GLY174.O 41.63%
B:ASN231.N-B:LEU227.O 36.45%
B:SER158.N-B:ASN151.O 39.64%
B:ASN95.ND2-B:TRP31.O 41.63%
B:HIS80.ND1-B:ASN63.OD1 36.45%
B:LEU32.N-B:VAL35.O 39.04%
B:ILE281.N-B:SER284.O 41.24%
B:ALA116.N-B:GLY124.O 35.66%
B:ASN95.ND2-B:TRP31.O 39.04%
B:ASP153.N-B:CYS156.O 41.04%
B:ASN151.ND2-B:THR111.O 35.26%
B:LEU205.N-B:THR201.O 38.84%
B:ASN231.N-B:LEU227.O 40.84%
B:TYR126.OH-B:LYS137.O 35.06%
B:TYR54.OH-B:ASP187.O 37.85%
B:ASN133.ND2-B:GLY195.O 40.04%
B:THR135.OG1-B:ASN133.OD1 34.46%
B:ASN231.N-B:LEU227.O 37.05%
B:LEU30.N-B:TYR37.O 38.84%
B:ASP153.N-B:CYS156.O 34.06%
B:CYS128.N-B:PHE112.O 35.86%
B:THR199.N-B:ASN238.O 38.05%
B:PHE112.N-B:CYS128.O 33.86%
B:ASP153.N-B:CYS156.O 35.86%
B:TYR239.N-B:ALA234.O 38.05%
B:THR111.OG1-B:ASP295.OD2 33.86%
B:ARG105.NH2-B:PHE181.O 35.26%
B:LEU205.N-B:THR201.O 36.65%
B:THR21.N-B:LEU67.O 33.47%
B:SER254.OG-B:ILE259.O 35.26%
B:ASN28.ND2-B:CYS145.O 35.86%
B:SER254.OG-B:ILE259.O 32.27%
B:THR111.OG1-B:ASP295.OD1 35.06%
B:GLU14.N-B:SER10.O 35.26%
B:TYR118.N-B:SER121.O 31.87%
B:THR111.OG1-B:ASP295.OD2 34.86%
B:TYR118.N-B:SER121.O 34.86%
B:SER113.N-B:PHE150.O 31.87%
B:GLU14.N-B:SER10.O 34.26%
B:ASN214.ND2-B:ALA210.O 34.06%
B:LYS269.N-B:CYS265.O 31.27%
B:THR21.N-B:LEU67.O 33.47%
B:THR21.N-B:LEU67.O 34.06%
B:ASN28.ND2-B:CYS145.O 31.08%
B:THR25.OG1-B:CYS44.O 32.87%
B:THR111.OG1-B:ASP295.OD1 34.06%
B:THR292.OG1-B:ASP295.OD1 30.88%
B:SER113.N-B:PHE150.O 32.47%
B:THR111.OG1-B:ASP295.OD2 33.86%
B:CYS22.N-B:THR25.O 30.28%
B:LEU268.N-B:MET264.O 32.27%
B:SER254.OG-B:ILE259.O 33.86%
B:ILE43.N-B:ARG40.O 29.88%
B:ALA255.N-B:GLY251.O 31.87%
B:PHE112.N-B:CYS128.O 33.47%
B:ARG40.NH2-B:ASP187.OD1 29.68%
B:THR135.OG1-B:ASN133.OD1 31.47%
B:TYR54.OH-B:ASP187.O 33.07%
B:LEU67.N-B:THR21.O 29.28%
B:CYS22.N-B:THR25.O 31.27%
B:SER158.N-B:ASN151.O 32.87%
B:TRP218.NE1-B:THR280.O 28.88%
B:ASN214.ND2-B:ALA210.O 29.88%
B:ALA173.N-B:MET165.O 32.27%
B:ALA173.N-B:MET165.O 28.29%
B:PHE112.N-B:CYS128.O 29.68%
B:ARG105.NH2-B:PHE181.O 31.47%
B:THR175.OG1-B:ASP176.O 28.09%
B:ARG4.N-B:GLN299.OE1 29.08%
B:ASN231.ND2-B:LEU242.O 31.27%
B:ARG60.NH2-B:ASP48.OD1 28.09%
B:THR175.OG1-B:ASP176.O 28.69%
B:ALA116.N-B:GLY124.O 31.27%
B:ARG40.NE-B:ASP187.OD2 27.89%
B:ALA116.N-B:GLY124.O 28.49%
B:ALA255.N-B:GLY251.O 30.68%
B:ALA255.N-B:GLY251.O 27.89%
B:ASN151.ND2-B:THR111.O 28.29%
B:CYS128.N-B:PHE112.O 30.08%
B:LEU208.N-B:VAL204.O 27.69%
B:GLN69.N-B:GLN19.O 27.89%
B:ASN95.ND2-B:GLY15.O 30.08%
B:GLN69.N-B:GLN19.O 27.69%
B:ASN95.ND2-B:GLY15.O 27.09%
B:HIS80.ND1-B:ASN63.OD1 30.08%
B:THR243.OG1-B:HIS246.ND1 27.49%
(continued)
2.4 Concluding Remarks
139
Table 2.46 (continued) SARS-CoV-2-N3 rep1
rep2
rep3
B:HIS80.ND1-B:ASN63.OD1 27.09%
B:ASN203.ND2-B:GLY109.O 29.68%
B:THR45.N-B:ASP48.OD2 27.29%
B:THR243.OG1-B:HIS246.ND1 26.89%
B:ILE136.N-B:HIS172.O 28.88%
B:PHE159.N-B:LYS102.O 27.09%
B:LYS269.N-B:CYS265.O 26.89%
B:SER62.N-B:ASN65.OD1 28.69%
B:VAL86.N-B:GLN83.O 26.49%
B:PHE159.N-B:LYS102.O 26.89%
B:VAL86.N-B:GLN83.O 28.69%
B:ASN221.N-B:SER267.OG 25.70%
B:LEU67.N-B:THR21.O 26.29%
B:CYS22.N-B:THR25.O 28.09%
B:LEU268.N-B:MET264.O 25.30%
B:TRP218.NE1-B:THR280.O 26.29%
B:ASN151.ND2-B:THR111.O 27.29%
B:ASN151.N-B:SER158.O 25.10%
B:ARG40.NH2-B:ASP187.OD1 25.90%
B:ILE200.N-B:ASP289.OD1 27.29%
B:ASN180.N-B:ASP176.OD2 24.90%
B:ASN203.ND2-B:GLY109.O 25.90%
B:LEU268.N-B:MET264.O 27.29%
B:ASN95.ND2-B:GLY15.O 24.50%
B:SER113.OG-B:GLN127.OE1 25.70%
B:SER113.OG-B:GLN127.OE1 26.89%
B:SER81.N-B:LYS88.O 24.30%
B:LEU272.N-B:LEU268.O 24.70%
B:LEU67.N-B:THR21.O 26.89%
B:ARG4.N-B:GLN299.OE1 24.30%
B:ASN231.ND2-B:LEU242.O 24.30%
B:ILE43.N-B:ARG40.O 26.49%
B:SER62.N-B:ASN65.OD1 24.10%
B:VAL104.N-B:PHE159.O 23.71%
B:GLN69.N-B:GLN19.O 26.49%
B:VAL104.N-B:PHE159.O 23.90%
B:ARG131.NH2-B:ASP289.OD1 23.71%
B:MET130.N-B:GLN110.O 26.29%
B:ARG105.NH1-B:ASP176.OD1 23.71%
B:LYS5.NZ-B:GLU290.OE1 23.31%
B:ARG4.N-B:GLN299.OE1 25.90%
B:CYS160.N-B:GLY149.O 23.71%
B:ARG40.NE-B:ASP187.OD2 22.91%
B:PHE159.N-B:LYS102.O 25.50%
B:CYS128.N-B:PHE112.O 22.91%
B:SER62.N-B:ASN65.OD1 22.91%
B:LYS269.N-B:CYS265.O 25.10%
B:MET165.N-B:ALA173.O 22.91%
B:LEU208.N-B:VAL204.O 22.71%
B:THR45.OG1-B:ASP48.OD1 25.10%
B:ARG131.NH2-B:ASP289.OD1 22.71%
B:SER284.N-B:ILE281.O 21.91%
B:THR175.OG1-B:ASP176.O 24.90%
B:ASN203.ND2-B:GLY109.O 22.51%
B:SER81.N-B:LYS88.O 21.91%
B:THR292.OG1-B:ASP295.OD1 24.10%
B:THR26.OG1-B:THR21.OG1 22.31%
B:LYS102.N-B:VAL157.O 21.71%
B:LYS102.N-B:VAL157.O 23.11%
B:THR292.OG1-B:ASP295.OD2 22.31%
B:ILE136.N-B:HIS172.O 21.51%
B:LEU208.N-B:VAL204.O 22.71%
B:CYS38.N-B:LEU87.O 22.11%
B:ALA210.N-B:ALA206.O 21.31%
B:TRP218.NE1-B:THR280.O 22.71%
B:ASN133.ND2-B:GLY195.O 21.91%
B:THR292.OG1-B:ASP295.OD2 21.31%
B:ASN151.N-B:SER158.O 22.31%
B:LYS102.N-B:VAL157.O 21.71%
B:ASN151.N-B:SER158.O 21.12%
B:ASN221.N-B:SER267.OG 22.31%
B:GLN107.N-B:GLN110.OE1 21.51%
B:ARG40.N-B:CYS85.O 21.12%
B:ALA234.N-B:PHE230.O 22.31%
B:THR198.OG1-B:GLU240.OE2 21.31%
B:ASN180.N-B:ASP176.OD2 20.12%
B:THR292.OG1-B:ASP295.OD2 22.31%
B:GLN273.N-B:LYS269.O 21.12%
B:THR292.N-B:ASP295.OD1 20.12%
B:THR45.OG1-B:ASP48.OD2 21.91%
B:THR21.OG1-B:THR26.OG1 20.32%
B:ARG60.NH1-B:ASP48.OD1 21.91%
B:ASN231.ND2-B:LEU242.O 20.32%
B:VAL104.N-B:PHE159.O 21.71%
B:GLN127.NE2-B:GLU290.OE2 20.32%
B:SER113.N-B:PHE150.O 21.51%
B:GLY29.N-B:VAL18.O 20.12%
B:THR292.N-B:ASP295.OD1 21.51%
B:VAL303.N-B:GLN256.O 20.12%
B:THR226.OG1-B:ASP229.OD2 21.51% B:SER284.N-B:ILE281.O 21.12% B:LYS5.NZ-B:GLU290.OE1 20.92% B:CYS160.N-B:GLY149.O 20.52% B:ASN180.N-B:ASP176.OD2 20.52% B:SER81.N-B:LYS88.O 20.52% B:THR98.OG1-B:ASP33.OD1 20.32% B:ASN238.ND2-B:ASP197.O 20.32% B:THR243.OG1-B:ASP245.OD1 20.12%
Table 2.47 The MD-SBs-HBs between the two monomers of dimer the SARS-CoV-1-Mpro1q2w model (denoted as “SARS-CoV-1 dimer”) and the SARS-CoV-2-Mpro-6y2e model (denoted as “SARS-CoV-2 dimer”), where each model has three sets of MD simulations [346] SARS-CoV-1 rep1
rep2
rep3
A:GLU14-B:LYS12
B:GLU14-A:LYS12
B:GLU14-A:LYS12
A:GLU290-B:ARG4
B:GLU290-A:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
A:TYR118.OH-B:ARG298.O 35.86%
A:SER139.OG-B:GLN299.OE1 54.38%
B:GLN299.NE2-A:SER139.O 47.61%
A:SER139.OG-B:GLY2.O 32.67%
B:VAL125.N-A:ALA7.O 34.46%
B:ARG4.NH1-A:GLU290.OE2 40.84%
A:ALA7.N-B:VAL125.O 28.69%
A:GLY11.N-B:GLU14.OE2 31.47%
A:ARG4.NH2-B:GLU290.OE2 39.04%
A:GLY11.N-B:GLU14.OE2 28.49%
A:VAL125.N-B:ALA7.O 31.27%
A:GLY11.N-B:GLU14.OE2 37.25%
B:ARG4.NH2-A:GLU290.OE1 30.08%
B:ALA7.N-A:VAL125.O 30.88%
A:ALA7.N-B:VAL125.O 32.27%
B:VAL125.N-A:ALA7.O 25.30%
B:ARG4.NH1-A:GLU290.OE1 29.88%
B:ARG4.NH2-A:GLU290.OE1 35.46%
B:ARG4.NH1-A:GLU290.OE2 24.30%
B:ARG4.NH2-A:GLU290.OE2 29.48%
A:TYR118.OH-B:ARG298.O 29.48%
B:GLY11.N-A:GLU14.OE2 23.71%
B:GLY11.N-A:GLU14.OE2 28.49%
A:ARG4.NH1-B:GLU290.OE1 28.29%
B:ARG4.NH2-A:GLU290.OE2 21.31%
A:ARG4.NH1-B:GLU290.OE1 22.51%
A:ARG4.NH2-B:GLU290.OE1 25.10%
A:ARG4.N-B:SER139.OG 20.32%
A:ARG4.NH2-B:GLU290.OE2 21.51%
A:VAL125.N-B:ALA7.O 20.12%
B:GLY11.N-A:GLU14.OE2 23.71% A:VAL125.N-B:ALA7.O 21.12%
(continued)
140
2 3C-Like Protease (3CLpro)
Table 2.47 (continued) SARS-CoV-2 rep1
rep2
rep3
A:GLU14-B:LYS12
A:GLU14-B:LYS12
A:GLU14-B:LYS12
B:GLU14-A:LYS12
A:GLU290-B:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
B:GLU290-A:ARG4
A:GLU290-B:ARG4 B:GLU290-A:ARG4 A:ASP216-B:LYS137
A:SER10.OG-A:GLU14.OE2 82.87%
B:SER139.OG-A:GLN299.OE1 64.34%
B:SER139.OG-A:GLN299.OE1 60.76%
A:SER267.OG-A:ASP263.O 65.94%
A:SER139.OG-B:GLN299.OE1 54.58%
A:SER139.OG-B:GLN299.OE1 48.80%
A:SER139.OG-B:GLN299.OE1 52.79%
B:ARG4.NH1-A:GLU290.OE2 50.00%
B:ARG4.NH1-A:GLU290.OE2 43.03%
B:SER139.OG-A:GLN299.OE1 46.02%
B:ARG4.NH2-A:GLU290.OE1 41.24%
B:ARG4.NH2-A:GLU290.OE1 33.67%
A:SER123.OG-B:VAL303.O 26.49%
B:VAL125.N-A:ALA7.O 34.06%
B:GLY11.N-A:GLU14.OE2 30.28%
B:SER1.OG-A:GLU166.OE2 29.08%
B:GLY11.N-A:GLU14.OE2 28.09%
A:GLY11.N-B:GLU14.OE2 30.08%
B:GLY11.N-A:GLU14.OE2 24.50%
B:SER1.OG-A:GLU166.OE1 23.90%
A:ARG4.NH2-B:GLU290.OE1 27.89%
B:SER1.OG-A:GLU166.OE1 24.10%
B:ASN119.ND2-A:PHE305.O 23.90%
A:VAL125.N-B:ALA7.O 26.10%
B:ARG4.NH1-A:GLU290.OE2 20.92%
A:ARG4.NH2-B:GLU290.OE1 22.51%
B:SER1.OG-A:GLU166.OE2 22.51%
B:SER1.N-A:PHE140.O 20.12%
B:SER1.OG-A:GLU166.OE2 21.71%
A:SER1.OG-B:GLU166.OE1 21.12%
B:PHE305.N-A:PRO122.O 21.12% A:ALA7.N-B:VAL125.O 20.92% A:PHE140.N-B:SER1.O 20.32% A:ARG4.NH1-B:GLU290.OE2 20.12%
Table 2.48 The MD-SBs-HBs between the two monomers of dimer the SARS-CoV-1-Mpro-N32hob model (denoted as “SARS-CoV-1-N3 dimer”) and the SARS-CoV-2-Mpro-N3-6lu7 model (denoted as “SARS-CoV-2-N3 dimer”), where each model has three sets of MD simulations [346] SARS-CoV-1-N3 rep1
rep2
rep3
A:GLU14-B:LYS12
B:GLU14-A:LYS12
A:GLU14-B:LYS12
A:GLU290-B:ARG4
A:GLU290-B:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
B:GLU290-A:ARG4
B:GLU290-A:ARG4
B:ARG4.NH2-A:GLU290.OE2 45.82%
A:SER139.OG-B:GLN299.OE1 59.36%
B:SER139.OG-A:GLN299.OE1 42.83%
B:ARG4.NH1-A:GLU290.OE1 43.23%
B:SER139.OG-A:GLY2.O 32.27%
A:SER1.OG-B:GLU166.OE2 29.88%
B:SER1.OG-A:GLU166.OE2 30.68%
A:VAL125.N-B:ALA7.O 29.08%
A:ALA7.N-B:VAL125.O 28.88%
B:GLY11.N-A:GLU14.OE1 30.28%
B:ARG4.NH2-A:GLU290.OE2 28.69%
A:ARG4.NH1-B:LYS137.O 28.49%
B:SER1.OG-A:GLU166.OE1 29.28%
A:ALA7.N-B:VAL125.O 28.29%
B:ARG4.NH1-A:GLU290.OE2 28.29%
A:SER1.OG-B:GLU166.OE1 27.69%
B:GLY11.N-A:GLU14.OE1 27.69%
B:ARG4.NH2-A:GLU290.OE1 26.49%
A:GLY11.N-B:GLU14.OE1 25.30%
B:ARG4.NH1-A:GLU290.OE1 23.90%
B:VAL125.N-A:ALA7.O 25.10%
A:SER139.OG-B:GLN299.OE1 23.11%
A:SER1.OG-B:GLU166.OE1 23.51%
A:SER1.OG-B:GLU166.OE1 23.31%
A:GLY143.N-B:VAL303.O 22.11%
B:VAL125.N-A:ALA7.O 22.71%
A:GLY11.N-B:GLU14.OE1 21.71%
A:VAL125.N-B:ALA7.O 21.91%
B:SER1.OG-A:GLU166.OE1 22.11%
B:ALA7.N-A:VAL125.O 20.92%
A:SER1.OG-B:GLU166.OE2 21.12%
B:ALA7.N-A:VAL125.O 21.91%
A:VAL125.N-B:ALA7.O 20.92%
SARS-CoV-2-N3 rep1
rep2
rep3
A:GLU288-B:ARG4
A:GLU14-B:LYS12
A:GLU14-B:LYS12
A:GLU290-B:ARG4
B:GLU14-A:LYS12
A:GLU290-B:ARG4
B:GLU290-A:ARG4
A:GLU290-B:ARG4
B:GLU290-A:ARG4
B:GLY11.N-A:GLU14.OE1 20.72%
B:GLU290-A:ARG4 A:SER139.OG-B:GLN299.OE1 57.57%
A:SER139.OG-B:GLN299.OE1 57.57%
A:SER139.OG-B:GLN299.OE1 58.37%
B:SER139.OG-A:GLN299.OE1 51.00%
B:SER139.OG-A:GLN299.OE1 53.19%
B:SER139.OG-A:GLN299.OE1 49.80%
B:VAL125.N-A:ALA7.O 32.67%
B:VAL125.N-A:ALA7.O 31.87%
B:GLY11.N-A:GLU14.OE1 33.47%
A:VAL125.N-B:ALA7.O 32.07%
B:SER1.OG-A:GLU166.OE1 31.67%
A:ALA7.N-B:VAL125.O 32.27%
B:SER1.OG-A:GLU166.OE2 30.68%
A:VAL125.N-B:ALA7.O 31.08%
A:GLY11.N-B:GLU14.OE1 30.68%
B:GLY11.N-A:GLU14.OE1 29.68%
B:GLY11.N-A:GLU14.OE1 28.88%
B:VAL125.N-A:ALA7.O 29.88%
A:GLY11.N-B:GLU14.OE1 29.28%
B:ARG4.NH1-A:GLU290.OE1 28.49%
B:SER1.OG-A:GLU166.OE2 24.30%
A:ALA7.N-B:VAL125.O 26.49%
A:ALA7.N-B:VAL125.O 27.69%
B:ALA7.N-A:VAL125.O 21.91%
A:SER1.OG-B:GLU166.OE2 26.29%
A:GLY11.N-B:GLU14.OE1 27.69%
B:SER1.OG-A:GLU166.OE1 21.71%
A:SER1.OG-B:GLU166.OE1 26.29%
B:ARG4.NH2-A:GLU290.OE2 25.90%
B:ARG4.NH2-A:GLU290.OE2 20.32%
B:ALA7.N-A:VAL125.O 26.10%
B:ALA7.N-A:VAL125.O 25.10%
B:ARG4.NH2-A:GLU290.OE1 20.12%
A:ARG4.NH2-B:GLU290.OE2 25.70%
B:SER1.OG-A:GLU166.OE2 22.11%
B:ARG4.NH1-A:GLU290.OE1 24.90%
A:ARG4.NH2-B:GLU290.OE2 21.12%
B:SER1.OG-A:GLU166.OE1 23.31%
A:ARG4.NH1-B:GLU290.OE2 20.92%
A:ARG4.NH1-B:GLU290.OE1 22.91%
A:ARG4.NH2-B:GLU290.OE1 20.32%
B:ARG4.NH2-A:GLU290.OE2 22.71%
A:SER1.OG-B:GLU166.OE2 20.12%
2.4 Concluding Remarks
141
Table 2.49 MD-SBs of the Mpro-wt-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php) A-chain – rep1
A-chain – rep2
A-chain – rep3
B-chain – rep1
B-chain – rep2
B-chain – rep3
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS102
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP155-LYS102
ASP155-LYS102
ASP155-LYS12
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP155-LYS12
ASP176-ARG105
ASP176-ARG105
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP176-ARG105
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP187-ARG40
ASP197-ARG131
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP216-ARG279
ASP216-ARG279
ASP216-ARG279
ASP197-LYS137
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP229-LYS269
ASP229-LYS269
ASP216-ARG279
ASP229-LYS269
ASP229-LYS269
ASP263-ARG222
ASP263-ARG222
ASP263-ARG222
ASP229-LYS269
ASP263-ARG222
ASP263-ARG222
ASP289-ARG131
ASP289-ARG131
ASP289-ARG131
ASP263-ARG222
ASP289-ARG131
ASP289-ARG131
ASP295-ARG298
ASP295-ARG298
ASP295-ARG298
ASP289-ARG131
ASP295-ARG298
ASP295-ARG298
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP295-ARG298
ASP34-LYS90
ASP34-LYS90
ASP48-LYS61
ASP48-ARG60
ASP48-ARG60
ASP34-LYS90
ASP48-ARG60
ASP48-ARG60
ASP56-ARG60
ASP48-LYS61
ASP48-LYS61
ASP48-ARG60
ASP48-LYS61
ASP56-ARG60
ASP92-ARG76
ASP56-ARG188
ASP56-ARG60
ASP48-LYS61
ASP56-ARG60
ASP92-ARG76
GLU178-LYS88
ASP56-ARG60
ASP92-ARG76
ASP56-ARG60
ASP92-ARG76
GLU270-LYS269
GLU270-LYS269
ASP92-ARG76
GLU270-LYS269
ASP92-ARG76
GLU178-ARG105
GLU288-LYS5
GLU288-LYS5
GLU178-LYS88
GLU288-LYS5
GLU178-ARG105
GLU270-ARG222
GLU290-ARG131
GLU290-ARG131
GLU270-LYS269
GLU270-LYS269
GLU290-LYS137
GLU290-LYS137
GLU288-LYS5
GLU47-ARG60
GLU270-LYS269
GLU288-LYS5
GLU290-LYS5
GLU290-LYS5
GLU290-ARG131
GLU55-ARG188
GLU290-LYS5
GLU288-LYS5
GLU270-ARG222
GLU290-ARG131
GLU55-ARG188
GLU290-LYS137
GLU55-ARG40
GLU290-ARG131
GLU290-LYS137
GLU55-ARG40
GLU290-LYS5
GLU55-ARG60
GLU290-LYS5
GLU290-LYS5 GLU47-ARG188
GLU47-ARG60
GLU47-ARG188
GLU55-ARG40
GLU55-ARG188
GLU55-ARG60
GLU55-ARG40
Table 2.50 MD-SBs of the Mpro-delP168-and-a173v-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php) A-chain – rep1
A-chain – rep2
A-chain – rep3
B-chain – rep1
B-chain – rep2
B-chain – rep3
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP155-LYS102
ASP155-LYS102
ASP155-LYS12
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP155-LYS12
ASP155-LYS12
ASP176-ARG105
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP176-ARG105
ASP176-ARG105
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP187-ARG40
ASP187-ARG40
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-ARG131
ASP197-ARG131
ASP197-LYS137
ASP216-ARG279
ASP229-LYS269
ASP216-ARG279
ASP197-LYS137
ASP197-LYS137
ASP216-ARG279
ASP229-LYS269
ASP263-ARG222
ASP229-LYS269
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP263-ARG222
ASP289-ARG131
ASP263-ARG222
ASP229-LYS269
ASP229-LYS269
ASP263-ARG222
ASP289-ARG131
ASP295-ARG298
ASP289-ARG131
ASP263-ARG222
ASP263-ARG222
ASP289-ARG131
ASP295-ARG298
ASP33-LYS100
ASP295-ARG298
ASP289-ARG131
ASP289-ARG131
ASP295-ARG298
ASP34-LYS90
ASP34-LYS90
ASP33-LYS100
ASP295-ARG298
ASP295-ARG298
ASP34-LYS90
ASP48-ARG188
ASP48-ARG60
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP48-ARG60 ASP48-LYS61
ASP48-ARG60
ASP48-LYS61
ASP48-ARG188
ASP48-ARG60
ASP48-ARG60
ASP48-LYS61
ASP56-ARG60
ASP48-ARG60
ASP48-LYS61
ASP48-LYS61
ASP56-ARG60
ASP92-ARG76
ASP48-LYS61
ASP56-ARG60
ASP56-ARG60
ASP92-ARG76
ASP92-ARG76
GLU270-LYS269
ASP56-ARG60
ASP92-ARG76
ASP92-ARG76
GLU178-ARG105
ASP56-ARG60
(continued)
142
2 3C-Like Protease (3CLpro)
Table 2.50 (continued) A-chain – rep1
A-chain – rep2
A-chain – rep3
B-chain – rep1
B-chain – rep2
GLU270-ARG222
GLU288-LYS5
ASP92-ARG76
GLU270-LYS269
GLU270-ARG222
GLU270-ARG222
GLU270-LYS269
GLU290-ARG131
GLU270-ARG279
GLU288-LYS5
GLU270-LYS269
GLU270-LYS269
B-chain – rep3
GLU288-LYS5
GLU290-LYS137
GLU270-LYS269
GLU290-ARG131
GLU288-LYS5
GLU288-LYS5
GLU290-ARG131
GLU290-LYS5
GLU288-LYS5
GLU290-LYS137
GLU290-ARG131
GLU290-ARG131
GLU290-LYS137
GLU55-ARG188
GLU290-LYS5
GLU55-ARG40
GLU47-ARG188
GLU290-ARG131
GLU290-LYS5
GLU290-LYS5
GLU290-LYS5
GLU290-LYS137
GLU55-ARG40
GLU55-ARG188
GLU55-ARG188
GLU290-LYS5
GLU55-ARG60
GLU55-ARG40
GLU55-ARG40
GLU47-ARG60
GLU47-ARG60
GLU47-LYS61
GLU47-LYS61
GLU55-ARG188
GLU55-ARG188
GLU55-ARG40
GLU55-ARG40
Table 2.51 MD-SBs of the Mpro-delP168-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php) A-chain – rep1
A-chain – rep2
A-chain – rep3
B-chain – rep1
B-chain – rep2
B-chain – rep3
ASP153-ARG298
ASP153-ARG298
ASP153-LYS102
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-LYS102
ASP153-LYS102
ASP155-LYS100
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP155-LYS100
ASP155-LYS100
ASP155-LYS102
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP155-LYS102
ASP155-LYS102
ASP155-LYS102
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP229-LYS269
ASP229-LYS269
ASP216-ARG279
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP263-ARG222
ASP263-ARG222
ASP229-LYS269
ASP229-LYS269
ASP216-ARG279
ASP216-ARG279
ASP289-ARG131
ASP289-ARG131
ASP263-ARG222
ASP263-ARG222
ASP229-LYS269
ASP229-LYS269
ASP295-ARG298
ASP295-ARG298
ASP289-ARG131
ASP289-ARG131
ASP263-ARG222
ASP263-ARG222
ASP34-LYS90
ASP33-LYS100
ASP295-ARG298
ASP295-ARG298
ASP289-ARG131
ASP289-ARG131
ASP48-ARG60
ASP34-LYS90
ASP34-LYS90
ASP34-LYS90
ASP295-ARG298
ASP295-ARG298
ASP48-LYS61
ASP48-ARG188
ASP48-ARG60
ASP48-ARG60
ASP34-LYS90
ASP34-LYS90
ASP56-ARG60
ASP48-ARG60
ASP56-ARG60
ASP48-LYS61
ASP48-ARG188
ASP48-ARG60
ASP92-ARG76
ASP48-LYS61
ASP92-ARG76
ASP56-ARG60
ASP48-ARG60
ASP48-LYS61
GLU270-ARG222
ASP56-ARG60
GLU270-LYS269
ASP92-ARG76
ASP48-LYS61
ASP56-ARG60
GLU270-LYS269
ASP92-ARG76
GLU288-LYS5
GLU270-ARG222
ASP56-ARG60
ASP92-ARG76
GLU288-LYS5
GLU270-LYS269
GLU290-ARG131
GLU270-LYS269
ASP92-ARG76
GLU270-LYS269
GLU290-ARG131
GLU288-LYS5
GLU290-LYS137
GLU288-LYS5
GLU270-ARG222
GLU288-LYS5
GLU290-LYS137
GLU290-ARG131
GLU290-LYS5
GLU290-ARG131
GLU270-LYS269
GLU290-ARG131
GLU290-LYS5
GLU290-LYS137
GLU47-LYS61
GLU290-LYS137
GLU288-LYS5
GLU290-LYS137
GLU55-ARG188
GLU290-LYS5
GLU55-ARG40
GLU290-LYS5
GLU290-ARG131
GLU290-LYS5
GLU55-ARG40
GLU47-ARG60
GLU55-ARG188
GLU290-LYS137
GLU47-ARG188
GLU55-ARG40
GLU55-ARG40
GLU290-LYS5
GLU47-ARG60
GLU47-ARG60
GLU47-LYS61
GLU47-LYS61
GLU55-ARG188
GLU55-ARG188
GLU55-ARG40
GLU55-ARG60
GLU55-ARG40
2.4 Concluding Remarks
143
Table 2.52 MD-SBs of the Mpro-a173v-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php) A-chain – rep1
A-chain – rep2
A-chain – rep3
B-chain – rep1
B-chain – rep2
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-ARG298
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
ASP153-LYS102
B-chain – rep3
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS100
ASP155-LYS12
ASP155-LYS12
ASP155-LYS12
ASP155-LYS102
ASP155-LYS102
ASP155-LYS102
ASP176-ARG105
ASP176-ARG105
ASP176-ARG105
ASP155-LYS12
ASP155-LYS12
ASP176-ARG105
ASP187-ARG188
ASP187-ARG188
ASP187-ARG188
ASP176-ARG105
ASP176-ARG105
ASP187-ARG188
ASP187-ARG40
ASP187-ARG40
ASP187-ARG40
ASP187-ARG188
ASP187-ARG188
ASP187-ARG40
ASP197-ARG131
ASP197-ARG131
ASP197-ARG131
ASP187-ARG40
ASP187-ARG40
ASP197-ARG131
ASP197-LYS137
ASP197-LYS137
ASP197-LYS137
ASP197-ARG131
ASP197-ARG131
ASP197-LYS137
ASP216-ARG279
ASP216-ARG279
ASP229-LYS269
ASP197-LYS137
ASP197-LYS137
ASP216-ARG279
ASP229-LYS269
ASP229-LYS269
ASP263-ARG222
ASP229-LYS269
ASP216-ARG279
ASP229-LYS269
ASP263-ARG222
ASP263-ARG222
ASP289-ARG131
ASP263-ARG222
ASP229-LYS269
ASP263-ARG222
ASP289-ARG131
ASP289-ARG131
ASP295-ARG298
ASP289-ARG131
ASP263-ARG222
ASP289-ARG131
ASP295-ARG298
ASP295-ARG298
ASP34-LYS90
ASP295-ARG298
ASP289-ARG131
ASP295-ARG298
ASP34-LYS90
ASP34-LYS90
ASP48-ARG60
ASP34-LYS90
ASP295-ARG298
ASP33-LYS100
ASP48-ARG60
ASP48-ARG60
ASP48-LYS61
ASP48-ARG60
ASP34-LYS90
ASP34-LYS90
ASP48-LYS61
ASP48-LYS61
ASP56-ARG60
ASP48-LYS61
ASP48-ARG60
ASP48-ARG60
ASP56-ARG60
ASP56-ARG60
ASP92-ARG76
ASP56-ARG60
ASP48-LYS61
ASP48-LYS61
ASP92-ARG76
ASP92-ARG76
GLU178-LYS88
ASP92-ARG76
ASP56-ARG60
ASP56-ARG60
GLU178-ARG105
GLU270-ARG222
GLU270-LYS269
GLU270-LYS269
ASP92-ARG76
ASP92-ARG76
GLU270-ARG222
GLU270-LYS269
GLU288-LYS5
GLU288-LYS5
GLU270-LYS269
GLU178-ARG105
GLU270-LYS269
GLU288-LYS5
GLU290-ARG131
GLU290-ARG131
GLU288-LYS5
GLU178-LYS88
GLU288-LYS5
GLU290-ARG131
GLU290-LYS137
GLU290-LYS5
GLU290-ARG131
GLU270-LYS269
GLU290-ARG131
GLU290-LYS137
GLU290-LYS5
GLU47-ARG60
GLU290-LYS5
GLU288-LYS5
GLU290-LYS137
GLU290-LYS5
GLU47-ARG60
GLU47-LYS61
GLU47-LYS61
GLU290-ARG131
GLU290-LYS5
GLU47-LYS61
GLU55-ARG188
GLU55-ARG188
GLU290-LYS137
GLU47-ARG188
GLU55-ARG188
GLU55-ARG40
GLU55-ARG40
GLU290-LYS5
GLU47-ARG60
GLU55-ARG40
GLU47-LYS61 GLU55-ARG188 GLU55-ARG40
GLU47-LYS61 GLU55-ARG188
MET162.N-THR175.O 47.01
LYS5.NZ-GLU290.OE2 46.82
ARG40.NH2-ASP187.OD1 46.64
SER144.OG-LEU141.O 45.74
TYR239.N-ALA234.O 48.09
LYS90.N-GLY79.O 46.82
MET162.N-THR175.O 45.92
LEU268.N-MET264.O 45.55
ARG40.NE-ASP187.OD2 47.55
LEU242.N-ASN231.OD1 47.37
LEU242.N-ASN231.OD1 48.46
ASN231.N-LEU227.O 48.28
GLY109.N-MET130.O 48.82
SER123.N-ALA116.O 48.28
LEU75.N-VAL68.O 48.82
SER144.OG-LEU141.O 48.82
LEU268.N-MET264.O 45.01 THR201.OG1-GLU240.O 44.83
ASN231.N-LEU227.O 48.28 LYS5.NZ-GLU290.OE1 47.91
LEU75.N-VAL68.O 46.28 PHE8.N-SER113.OG 45.74
LEU75.N-VAL68.O 49.18 GLY109.N-MET130.O 49.00
TYR239.N-ALA234.O 46.82 LYS88.N-SER81.O 46.28
ARG131.NH1-ASP289.OD1 49.73 THR201.OG1-GLU240.O 49.55
GLY120.N-ASN28.OD1 47.01 LYS90.N-GLY79.O 47.01
VAL157.N-LYS100.O 50.09 LYS88.N-SER81.O 49.73
LEU115.N-VAL148.O 49.91 ARG131.NH2-ASP289.OD1 47.19
ILE78.N-LYS90.O 50.45 SER123.N-ALA116.O 50.09
THR257.OG1-LEU253.O 50.45
LYS90.N-GLY79.O 49.91
ARG131.NH1-ASP289.OD1 49.73
VAL91.N-ASP34.O 49.18
ASN231.N-LEU227.O 50.27 HSE172.N-ILE136.O 50.09
THR257.OG1-LEU253.O 51.00 HSE172.N-ILE136.O 50.45
HSE172.N-ILE136.O 51.18
LEU75.N-VAL68.O 50.45
VAL157.N-LYS100.O 51.54
GLY146.N-HSE163.O 50.27
GLY146.N-HSE163.O 51.72 GLY109.N-MET130.O 51.00 THR257.OG1-LEU253.O 51.00
SER147.OG-SER144.O 52.27 ASN95.N-ASP33.O 52.09 TYR239.N-ALA234.O 51.00
THR21.N-LEU67.O 53.36
VAL157.N-LYS100.O 53.18
ASN231.N-LEU227.O 52.63
HSE172.N-ILE136.O 53.36
THR201.OG1-GLU240.O 53.36
THR21.N-LEU67.O 54.81 ARG40.NH2-ASP187.OD2 52.99
GLY146.N-HSE163.O 53.72 LEU115.N-VAL148.O 52.45
VAL157.N-LYS100.O 56.62 SER123.N-ALA116.O 55.54
TYR37.N-LEU30.O 54.45 LYS90.N-GLY79.O 54.26
VAL20.N-LEU27.O 57.71 ASN95.N-ASP33.O 56.81
VAL20.N-LEU27.O 55.90
SER123.N-ALA116.O 51.91
ARG105.NH2-PHE181.O 55.90
LYS88.N-SER81.O 53.90
VAL20.N-LEU27.O 54.63
LEU89.N-VAL36.O 54.08
SER267.OG-ASP263.O 56.99
GLY146.N-HSE163.O 56.62
ARG105.NH2-PHE181.O 56.99
LEU115.N-VAL148.O 56.62
TYR37.N-LEU30.O 58.26
ASN95.N-ASP33.O 58.08
ARG40.NH2-ASP187.OD2 58.08
ASN95.N-ASP33.O 57.71
ARG105.NH2-PHE181.O 55.17
SER254.OG-ILE259.O 59.71 GLY149.N-TYR161.O 59.53
GLY149.N-TYR161.O 58.98
TYR182.OH-CYS160.O 59.35
GLY149.N-TYR161.O 59.17
SER254.OG-ILE259.O 58.62
THR257.OG1-LEU253.O 58.26 LEU89.N-VAL36.O 58.62
TYR37.N-LEU30.O 61.89 ARG40.NE-ASP187.OD1 61.52 LEU89.N-VAL36.O 60.98
LEU167.N-VAL171.O 62.98 SER267.OG-ASP263.O 60.25 SER254.OG-ILE259.O 60.07
SER254.OG-ILE259.O 59.89
LEU89.N-VAL36.O 59.53
SER267.OG-ASP263.O 62.43
LEU167.N-VAL171.O 59.53
TYR182.OH-CYS160.O 64.43 SER267.OG-ASP263.O 64.07
TYR182.OH-CYS160.O 64.97 VAL114.N-TYR126.O 64.61
SER10.OG-GLU14.OE2 61.52
VAL20.N-LEU27.O 60.44
TYR37.N-LEU30.O 63.88
GLY149.N-TYR161.O 62.61
LEU167.N-VAL171.O 62.25
SER10.OG-GLU14.OE2 65.88 LEU167.N-VAL171.O 65.15
VAL36.N-LEU89.O 69.87 ARG131.NH2-ASP289.OD2 69.33
ARG131.NH2-ASP289.OD2 62.25
LEU115.N-VAL148.O 61.89
VAL114.N-TYR126.O 66.79
HSE163.N-SER147.O 65.15
TYR182.OH-CYS160.O 59.89
VAL36.N-LEU89.O 69.33 VAL114.N-TYR126.O 66.79
ARG40.NH2-ASP187.OD1 73.32 HSE163.N-SER147.O 71.69
VAL114.N-TYR126.O 67.33
VAL36.N-LEU89.O 66.79
TRP31.N-CYS16.O 70.05
VAL36.N-LEU89.O 67.88
HSE163.N-SER147.O 70.05
TRP31.N-CYS16.O 73.50
HSE163.N-SER147.O 72.78
ARG40.NE-ASP187.OD1 75.14
ARG131.NH2-ASP289.OD2 67.51
B-chain – rep1 TRP31.N-CYS16.O 70.42
A-chain – rep3 ARG40.NE-ASP187.OD2 78.04
A-chain – rep2
TRP31.N-CYS16.O 75.14
A-chain – rep1
GLY29.N-VAL18.O 46.10
LEU67.N-THR21.O 46.82
PHE8.N-SER113.OG 47.37
LEU242.N-ASN231.OD1 47.73
SER144.OG-LEU141.O 47.73
TYR239.N-ALA234.O 48.46
LEU115.N-VAL148.O 49.00
LEU87.N-CYS38.O 49.18
GLY120.N-ASN28.OD1 49.18
LYS90.N-GLY79.O 49.36
GLY146.N-HSE163.O 50.09
ASN231.N-LEU227.O 50.09
ILE78.N-LYS90.O 50.82
THR201.OG1-GLU240.O 51.36
LYS88.N-SER81.O 51.72
LEU75.N-VAL68.O 51.91
VAL157.N-LYS100.O 51.91
THR257.OG1-LEU253.O 53.72
LEU89.N-VAL36.O 53.90
SER254.OG-ILE259.O 55.35
HSE172.N-ILE136.O 55.90
SER123.N-ALA116.O 56.26
GLY109.N-MET130.O 56.44
ASN95.N-ASP33.O 58.44
VAL20.N-LEU27.O 58.62
TYR182.OH-CYS160.O 60.07
SER267.OG-ASP263.O 60.44
TYR37.N-LEU30.O 61.16
GLY149.N-TYR161.O 63.70
LEU167.N-VAL171.O 65.52
VAL114.N-TYR126.O 67.15
VAL36.N-LEU89.O 67.51
HSE163.N-SER147.O 70.24
TRP31.N-CYS16.O 72.60
B-chain – rep2
GLY29.N-VAL18.O 46.28
LEU242.N-ASN231.OD1 46.82
TYR182.N-GLY174.O 47.01
LEU205.N-THR201.O 47.55
ASN231.N-LEU227.O 48.64
VAL91.N-ASP34.O 48.64
PHE8.N-SER113.OG 48.64
ILE78.N-LYS90.O 48.82
ARG105.NH2-PHE181.O 49.73
TYR239.N-ALA234.O 51.00
LEU75.N-VAL68.O 51.00
LEU167.N-VAL171.O 51.18
GLY109.N-MET130.O 51.54
VAL157.N-LYS100.O 51.54
ILE136.N-HSE172.O 52.27
THR257.OG1-LEU253.O 53.18
LYS88.N-SER81.O 53.36
ARG40.NE-ASP187.OD1 54.26
THR175.OG1-ASP176.O 54.81
TYR182.OH-CYS160.O 54.81
LEU89.N-VAL36.O 54.81
LYS90.N-GLY79.O 56.08
TYR37.N-LEU30.O 56.99
GLY149.N-TYR161.O 57.89
SER123.N-ALA116.O 57.89
LEU115.N-VAL148.O 58.08
SER254.OG-ILE259.O 58.44
VAL20.N-LEU27.O 59.71
ASN95.N-ASP33.O 59.89
SER267.OG-ASP263.O 60.25
VAL36.N-LEU89.O 68.60
VAL114.N-TYR126.O 70.96
HSE163.N-SER147.O 72.23
TRP31.N-CYS16.O 77.13
B-chain – rep3
Table 2.53 MD-HBs (with occupancy rates ≥30%) of the Mpro-wt-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
144 2 3C-Like Protease (3CLpro)
LEU87.N-CYS38.O 43.74 LEU242.N-ASN231.OD1 43.38 GLN83.N-VAL86.O 42.83
SER144.OG-LEU141.O 43.74 ALA70.N-VAL73.O 43.19 LEU87.N-CYS38.O 43.01
ARG131.NH1-ASP289.OD1 43.92
PHE150.N-SER113.O 42.65
GLY29.N-VAL18.O 42.65
LEU205.N-THR201.O 42.47
ASN274.N-GLU270.O 42.47
GLN83.N-VAL86.O 42.47
VAL18.N-GLY29.O 42.11
GLY109.N-MET130.O 44.28
SER147.OG-SER144.O 44.10
LYS5.NZ-GLU290.OE1 44.10
GLN69.N-GLN19.O 43.92
THR21.N-LEU67.O 43.56
LEU27.N-VAL20.O 43.56
GLY120.N-ASN28.OD1 43.56
LEU87.N-CYS38.O 43.38
SER144.OG-LEU141.O 39.20 TYR54.OH-ASP187.OD1 39.02
MET130.N-GLN110.O 39.93 GLN19.N-GLN69.O 39.56
ILE78.N-LYS90.O 41.20
VAL91.N-ASP34.O 40.83
PHE8.N-SER113.OG 40.65
ARG105.NH1-ASP176.OD2 40.47
ALA70.N-VAL73.O 40.11
LEU87.N-CYS38.O 39.75
THR169.OG1-PRO168.O 41.56
ASN274.N-GLU270.O 41.02
LYS88.N-SER81.O 41.02
LEU67.N-THR21.O 40.65
SER254.N-LEU250.O 40.29
GLN19.N-GLN69.O 40.29
ASP153.N-CYS156.O 39.93
LEU27.N-VAL20.O 37.93
MET130.N-GLN110.O 37.57
PHE159.N-LYS102.O 37.57
ILE200.N-ASP289.OD2 37.57
ILE281.N-SER284.O 37.39
ILE78.N-LYS90.O 38.66
ARG105.NH1-ASP176.OD1 38.48
TYR54.OH-ASP187.OD1 38.29
ILE200.N-ASP289.OD2 37.75
CYS128.N-PHE112.O 37.02
LEU205.N-THR201.O 36.30 ARG131.NH1-ASP289.OD2 36.30
SER113.N-PHE150.O 36.12
ARG105.NH2-PHE181.O 36.48
THR21.N-LEU67.O 36.12
CYS160.N-GLY149.O 36.30
LEU272.N-LEU268.O 36.48
LEU67.N-THR21.O 38.29
LEU205.N-THR201.O 38.84 TYR182.N-GLY174.O 36.66
MET130.N-GLN110.O 37.02
LYS269.N-CYS265.O 37.02
CYS160.N-GLY149.O 38.48
LEU272.N-LEU268.O 39.20 ASN180.N-ASP176.OD2 37.02
CYS128.N-PHE112.O 37.39
ALA234.N-PHE230.O 37.21
ALA116.N-GLY124.O 38.84
ALA173.N-MET165.O 39.20
PHE150.N-SER113.O 36.84
VAL91.N-ASP34.O 37.39
ASN221.N-SER267.OG 37.57
SER254.N-LEU250.O 39.20
PHE150.N-SER113.O 39.38
ILE78.N-LYS90.O 37.02
ASN221.N-SER267.OG 37.57
GLN69.N-GLN19.O 37.93
ALA234.N-PHE230.O 39.38
LEU268.N-MET264.O 36.84
LEU67.N-THR21.O 37.93
LEU30.N-TYR37.O 38.48
SER158.N-ASN151.O 38.11
GLN19.N-GLN69.O 39.38
VAL18.N-GLY29.O 40.47
THR243.OG1-HSE246.ND1 41.20
ALA116.N-GLY124.O 41.92
ALA234.N-PHE230.O 38.29
GLN69.N-GLN19.O 39.38
SER254.N-LEU250.O 40.65
GLY120.N-ASN28.OD1 41.38
SER158.N-ASN151.O 42.11
SER10.OG-GLU14.OE1 38.84
PHE150.N-SER113.O 39.75
ASN180.N-ASP176.OD1 40.83
GLN19.N-GLN69.O 41.38
ASN221.N-SER267.OG 42.47
LEU272.N-LEU268.O 39.02
SER254.N-LEU250.O 40.47
GLY29.N-VAL18.O 40.83
LEU272.N-LEU268.O 41.74
MET130.N-GLN110.O 43.01
LEU30.N-TYR37.O 38.66
MET162.N-THR175.O 41.02
ASN274.N-GLU270.O 41.38
ASN180.N-ASP176.OD1 41.74
VAL91.N-ASP34.O 39.38
ALA70.N-VAL73.O 41.02
ALA116.N-GLY124.O 41.38
ALA116.N-GLY124.O 41.38
VAL18.N-GLY29.O 41.56
LEU205.N-THR201.O 42.65 MET162.N-THR175.O 41.74
ASP153.N-CYS156.O 41.56
GLN83.N-VAL86.O 42.83
GLY29.N-VAL18.O 43.92
GLY120.N-ASN28.OD1 45.19
LEU30.N-TYR37.O 43.92
PHE8.N-SER113.OG 44.65
LEU27.N-VAL20.O 44.10
LEU242.N-ASN231.OD1 45.92
TYR239.N-ALA234.O 44.83
SER147.OG-SER144.O 44.28
VAL18.N-GLY29.O 44.65
ASN274.N-GLU270.O 44.46
LEU67.N-THR21.O 46.64
THR201.OG1-GLU240.O 45.55
PHE8.N-SER113.OG 47.91
SER147.OG-SER144.O 45.74
GLY29.N-VAL18.O 44.83
ASN180.N-ASP176.OD2 44.83
SER147.OG-SER144.O 36.48
PHE159.N-LYS102.O 36.48
MET162.N-THR175.O 36.48
SER10.OG-GLU14.OE2 36.48
ALA173.N-MET165.O 36.66
LYS269.N-CYS265.O 37.02
GLN69.N-GLN19.O 37.02
SER254.N-LEU250.O 37.02
THR175.OG1-ASP176.O 37.21
TYR182.N-GLY174.O 37.21
GLN83.N-VAL86.O 37.75
ASP153.N-CYS156.O 37.75
LEU30.N-TYR37.O 37.93
ASN203.ND2-ASP289.O 38.11
CYS128.N-PHE112.O 38.48
ALA234.N-PHE230.O 38.66
THR21.N-LEU67.O 39.20
ILE200.N-ASP289.OD2 39.38
LEU268.N-MET264.O 39.56
GLN19.N-GLN69.O 40.29
SER158.N-ASN151.O 40.65
PHE150.N-SER113.O 41.02
ASN274.N-GLU270.O 41.02
LEU27.N-VAL20.O 41.20
ALA70.N-VAL73.O 41.38
ARG40.NH2-ASP187.OD1 41.74
LEU272.N-LEU268.O 41.74
LEU205.N-THR201.O 43.38
VAL91.N-ASP34.O 43.92
ARG131.NH2-ASP289.OD2 44.46
ARG40.NE-ASP187.OD2 45.01
ALA116.N-GLY124.O 45.74
(continued)
GLN83.N-VAL86.O 35.39
LYS5.NZ-GLU290.OE2 35.57
LYS269.N-CYS265.O 36.12
ALA234.N-PHE230.O 36.30
CYS38.N-LEU87.O 36.48
ASP153.N-CYS156.O 37.57
GLY146.N-HSE163.O 37.75
ALA116.N-GLY124.O 37.93
ARG4.N-GLN299.OE1 39.20
THR21.N-LEU67.O 39.38
ASN221.N-SER267.OG 39.93
THR243.OG1-HSE246.ND1 39.93
MET162.N-THR175.O 40.11
VAL18.N-GLY29.O 40.47
LEU87.N-CYS38.O 40.83
GLN19.N-GLN69.O 41.20
LEU272.N-LEU268.O 41.20
SER147.OG-SER144.O 41.56
SER158.N-ASN151.O 41.56
HSE172.N-ILE136.O 41.92
LEU27.N-VAL20.O 42.29
TYR118.N-SER121.O 42.29
LEU30.N-TYR37.O 42.29
LEU268.N-MET264.O 43.01
CYS128.N-PHE112.O 43.38
THR201.OG1-GLU240.O 43.56
PHE150.N-SER113.O 44.46
THR135.OG1-ASN133.OD1 45.19
ASN274.N-GLU270.O 45.19
GLY120.N-ASN28.OD1 45.19
LEU67.N-THR21.O 45.37
ARG40.NH2-ASP187.OD2 45.74
2.4 Concluding Remarks 145
SER158.N-ASN151.O 35.03
ASN133.ND2-GLY195.O 34.12
LYS269.N-CYS265.O 33.94
SER113.OG-GLN127.OE1 33.94
ASN203.ND2-ASP289.O 33.94
ASN28.ND2-CYS145.O 32.67
ALA255.N-GLY251.O 32.30
THR45.N-ASP48.OD1 32.30
CYS128.N-PHE112.O 32.12
ASN133.ND2-GLY195.O 34.30
TYR209.OH-ILE259.O 34.12
LYS269.N-CYS265.O 33.58
SER10.OG-GLU14.OE1 33.39
CYS265.N-VAL261.O 32.85
SER267.N-ASP263.O 32.85
THR292.OG1-ASP295.OD2 32.67
THR175.OG1-ASP176.O 31.94
PHE112.N-CYS128.O 31.22
B-chain – rep1
THR175.OG1-ASP176.O 30.13 PHE112.N-CYS128.O 30.13
TYR118.N-SER121.O 30.13 CYS128.N-PHE112.O 30.13
TYR209.OH-ILE259.O 30.67
ILE106.N-TYR182.OH 30.49
THR169.OG1-PRO168.O 30.49 ILE136.N-HSE172.O 30.31
PHE112.N-CYS128.O 31.03 LEU32.N-VAL35.O 30.49
THR175.OG1-ASP176.O 30.85
ASN133.ND2-GLY195.O 30.67
ASN214.N-ALA210.O 30.85
GLN256.N-PRO252.O 30.85
ALA255.N-GLY251.O 31.03
ARG131.N-THR135.O 31.22
LYS5.NZ-GLU288.OE1 31.22
LYS5.NZ-GLU290.OE2 31.40
ILE281.N-SER284.O 31.94
ALA266.N-LEU262.O 32.12
CYS38.N-LEU87.O 32.30
TYR209.OH-ILE259.O 33.21
LYS269.N-CYS265.O 33.21
TYR118.N-SER121.O 34.30
SER267.N-ASP263.O 34.30
PHE159.N-LYS102.O 34.48
LYS5.NZ-GLU290.OE1 34.66
TYR182.N-GLY174.O 34.85
THR243.OG1-HSE246.ND1 35.03
CYS160.N-GLY149.O 35.39
ALA173.N-MET165.O 35.39
SER62.OG-LEU58.O 35.57
ASN203.ND2-ASP289.O 35.75
SER113.N-PHE150.O 30.67
ARG105.NH1-ASP176.OD2 31.40
ALA173.N-MET165.O 31.58
THR45.OG1-ASP48.OD2 32.12
PHE159.N-LYS102.O 32.12
GLN256.N-PRO252.O 32.30
SER158.N-ASN151.O 32.30
THR21.OG1-THR25.O 32.67
ILE281.N-SER284.O 32.85
CYS265.N-VAL261.O 33.21
THR169.OG1-PRO168.O 33.58
THR45.OG1-ASP48.OD1 33.58
THR135.OG1-ASN133.OD1 33.94
ILE200.N-ASP289.OD2 33.94
TYR209.OH-ILE259.O 31.22
THR45.OG1-ASP48.OD1 35.21
THR243.OG1-HSE246.ND1 34.85
ILE136.N-HSE172.O 33.94
PHE112.N-CYS128.O 31.03
LEU268.N-MET264.O 35.75
ALA70.N-VAL73.O 35.57
ALA255.N-GLY251.O 34.85
ALA266.N-LEU262.O 31.03
ASN221.N-SER267.OG 35.93
SER113.N-PHE150.O 35.75
THR243.OG1-HSE246.ND1 35.03
ASN203.ND2-GLY109.O 30.67
THR135.OG1-ASN133.OD1 36.30
ALA266.N-LEU262.O 35.75
LEU27.N-VAL20.O 35.21
GLN256.N-PRO252.O 30.49
CYS265.N-VAL261.O 36.48
PHE159.N-LYS102.O 36.12
ASN203.ND2-ASP289.O 35.39
GLN256.N-PRO252.O 31.40
ARG131.N-THR135.O 36.66
ALA255.N-GLY251.O 36.12
THR175.OG1-ASP176.O 35.39
ALA266.N-LEU262.O 35.75
TYR118.N-SER121.O 31.40
ALA173.N-MET165.O 36.84
ALA234.N-PHE230.O 36.30
A-chain – rep3 CYS38.N-LEU87.O 35.93
ASN203.ND2-ASP289.O 31.03
TYR182.N-GLY174.O 37.21
ILE281.N-SER284.O 30.67
A-chain – rep2
GLN69.N-GLN19.O 37.21
A-chain – rep1
ARG131.N-THR135.O 36.66
CYS160.N-GLY149.O 36.48
Table 2.53 (continued) B-chain – rep2
ARG131.NH1-ASP289.OD1 30.49
SER113.N-PHE150.O 30.49
CYS265.N-VAL261.O 30.49
THR169.OG1-PRO168.O 30.67
LYS5.NZ-GLU290.OE2 30.67
THR175.N-MET162.O 30.85
TYR118.N-SER121.O 31.03
PHE112.N-CYS128.O 31.22
ASN180.N-ASP176.OD2 31.40
ILE136.N-HSE172.O 31.40
TYR209.OH-ILE259.O 31.58
THR135.OG1-ASN133.OD1 31.94
ALA266.N-LEU262.O 32.30
LYS5.NZ-GLU290.OE1 32.30
MET130.N-GLN110.O 32.85
ALA255.N-GLY251.O 32.85
ASN221.N-SER267.OG 33.03
CYS160.N-GLY149.O 33.39
ARG131.N-THR135.O 33.94
VAL18.N-GLY29.O 34.48
ASN180.N-ASP176.OD1 34.66
ASN133.ND2-GLY195.O 35.03
THR243.OG1-HSE246.ND1 35.93
B-chain – rep3
CYS265.N-VAL261.O 30.13
GLN256.N-PRO252.O 30.31
THR292.OG1-ASP295.OD1 30.67
ASN214.N-ALA210.O 30.67
LYS5.NZ-GLU288.OE2 31.03
MET130.N-GLN110.O 31.22
ARG131.NH2-ASP289.OD2 31.76
ALA266.N-LEU262.O 32.12
THR175.N-MET162.O 32.49
ASN203.ND2-ASP289.O 32.49
CYS160.N-GLY149.O 32.67
ALA255.N-GLY251.O 32.67
ALA70.N-VAL73.O 32.85
GLN69.N-GLN19.O 32.85
SER139.N-TYR126.OH 33.21
LYS5.NZ-GLU290.OE1 33.76
SER254.N-LEU250.O 33.94
ILE281.N-SER284.O 34.48
ALA173.N-MET165.O 34.48
TYR209.OH-ILE259.O 34.85
PHE112.N-CYS128.O 34.85
PHE159.N-LYS102.O 35.39
ASN180.N-ASP176.OD1 35.39
146 2 3C-Like Protease (3CLpro)
TYR182.OH-CYS160.O 58.80
SER147.OG-SER144.O 52.81
GLY149.N-TYR161.O 53.54 ARG105.NH2-PHE181.O 53.54 SER123.N-ALA116.O 53.54
THR201.OG1-GLU240.O 55.35
VAL20.N-LEU27.O 55.17
GLY146.N-HSE163.O 54.45
LEU115.N-VAL148.O 52.45
TYR239.N-ALA234.O 52.09
THR257.OG1-LEU253.O 52.99
THR201.OG1-GLU240.O 52.27
ARG40.NE-ASP187.OD1 51.54
GLY146.N-HSE163.O 51.00
GLY109.N-MET130.O 51.00
ASN274.N-GLU270.O 45.92
MET162.N-THR175.O 45.55
LEU67.N-THR21.O 45.19
ASN274.N-GLU270.O 44.65
LEU87.N-CYS38.O 48.64
ILE136.N-HSE172.O 46.64
LEU87.N-CYS38.O 47.55
VAL173.N-MET165.O 47.37
GLY29.N-VAL18.O 47.37
GLN83.N-VAL86.O 46.10
LEU242.N-ASN231.OD1 45.74
SER147.OG-SER144.O 45.19
SER10.OG-GLU14.OE2 49.18 ARG131.NH1-ASP289.OD1 49.00
LYS90.N-GLY79.O 47.19 LEU205.N-THR201.O 47.01
LYS88.N-SER81.O 48.82
ILE78.N-LYS90.O 48.64
MET162.N-THR175.O 46.28
GLY120.N-ASN28.OD1 46.10
LEU67.N-THR21.O 47.55
PHE8.N-SER113.OG 45.55
GLY120.N-ASN28.OD1 46.64
MET162.N-THR175.O 47.91
LEU242.N-ASN231.OD1 45.55 THR175.OG1-ASP176.O 45.37
LYS90.N-GLY79.O 48.46
LEU75.N-VAL68.O 46.46
LYS88.N-SER81.O 49.55 VAL157.N-LYS100.O 49.18
THR201.OG1-GLU240.O 49.18 LEU67.N-THR21.O 48.28
LYS90.N-GLY79.O 49.73
ASN231.N-LEU227.O 49.55
ASN231.N-LEU227.O 48.09
LEU75.N-VAL68.O 46.46
THR257.OG1-LEU253.O 51.36 THR201.OG1-GLU240.O 49.91
GLY146.N-HSE163.O 49.36
GLY109.N-MET130.O 50.09
HSE172.N-ILE136.O 49.91
TYR239.N-ALA234.O 49.00
ASN231.N-LEU227.O 49.55
LEU75.N-VAL68.O 51.72
MET162.N-THR175.O 49.91 TYR239.N-ALA234.O 51.54
SER144.OG-LEU141.O 51.72
VAL157.N-LYS100.O 52.45 TYR239.N-ALA234.O 49.91
VAL20.N-LEU27.O 52.45
LEU87.N-CYS38.O 52.63
LEU115.N-VAL148.O 53.90
TYR182.OH-CYS160.O 56.62
HSE172.N-ILE136.O 48.82
SER123.N-ALA116.O 51.00
HSE172.N-ILE136.O 52.81
ASN95.N-ASP33.O 54.45
ARG105.NH2-PHE181.O 55.35
LYS90.N-GLY79.O 53.18
SER147.OG-SER144.O 50.27
ILE78.N-LYS90.O 53.72
LYS88.N-SER81.O 54.81
THR257.OG1-LEU253.O 55.72
ARG105.NH2-PHE181.O 54.08
LYS88.N-SER81.O 49.91
ARG105.NH2-PHE181.O 55.17
ILE78.N-LYS90.O 54.99
ASN95.N-ASP33.O 56.26
ILE78.N-LYS90.O 49.18
LEU89.N-VAL36.O 56.62
GLY109.N-MET130.O 55.72
GLY149.N-TYR161.O 57.17
ARG40.NH2-ASP187.OD2 54.63
LEU167.N-VAL171.O 56.81
LEU115.N-VAL148.O 55.17
GLY146.N-HSE163.O 58.80
LEU115.N-VAL148.O 56.26 THR257.OG1-LEU253.O 56.08
LEU89.N-VAL36.O 59.17
TYR37.N-LEU30.O 58.44
TYR37.N-LEU30.O 57.35
ASN95.N-ASP33.O 59.17
VAL20.N-LEU27.O 56.44
SER254.OG-ILE259.O 59.35
SER123.N-ALA116.O 55.17
GLY149.N-TYR161.O 59.53
SER254.OG-ILE259.O 56.62
SER254.OG-ILE259.O 59.89
SER267.OG-ASP263.O 59.89
ASN95.N-ASP33.O 60.25
SER267.OG-ASP263.O 57.35
VAL157.N-LYS100.O 60.25
LEU89.N-VAL36.O 60.80
VAL114.N-TYR126.O 66.06 TYR37.N-LEU30.O 64.97 SER267.OG-ASP263.O 60.62
LEU89.N-VAL36.O 61.52 TYR37.N-LEU30.O 58.80 HSE172.N-ILE136.O 58.08
ARG131.NH2-ASP289.OD2 64.61
LEU167.N-VAL171.O 62.25
VAL20.N-LEU27.O 61.34
TYR182.OH-CYS160.O 60.80
ARG131.NH2-ASP289.OD2 67.88 ARG40.NH2-ASP187.OD1 66.79
LEU167.N-VAL171.O 64.61 TYR182.OH-CYS160.O 64.07
ARG40.NH2-ASP187.OD1 70.05
VAL36.N-LEU89.O 67.88
SER254.OG-ILE259.O 63.34
SER267.OG-ASP263.O 63.16
LEU167.N-VAL171.O 61.16
HSE163.N-SER147.O 72.60 VAL36.N-LEU89.O 70.42
VAL36.N-LEU89.O 68.42 VAL114.N-TYR126.O 65.88
HSE163.N-SER147.O 71.32
VAL114.N-TYR126.O 71.14
VAL36.N-LEU89.O 70.05
VAL114.N-TYR126.O 65.52
GLY149.N-TYR161.O 60.98
TRP31.N-CYS16.O 73.32
TRP31.N-CYS16.O 71.32
B-chain – rep1
TRP31.N-CYS16.O 74.05
TRP31.N-CYS16.O 74.05
A-chain – rep3 ARG40.NE-ASP187.OD2 78.77
ARG40.NE-ASP187.OD2 77.50
HSE163.N-SER147.O 74.77 HSE163.N-SER147.O 75.50
A-chain – rep2
A-chain – rep1
ARG131.NH1-ASP289.OD1 46.46
SER147.OG-SER144.O 47.73
THR201.OG1-GLU240.O 47.91
LEU67.N-THR21.O 48.28
GLY29.N-VAL18.O 48.64
TYR239.N-ALA234.O 48.82
ILE78.N-LYS90.O 49.36
LYS90.N-GLY79.O 49.91
ASN231.N-LEU227.O 49.91
THR257.OG1-LEU253.O 49.91
VAL157.N-LYS100.O 51.18
GLY146.N-HSE163.O 51.91
LEU87.N-CYS38.O 51.91
GLY109.N-MET130.O 51.91
HSE172.N-ILE136.O 52.27
LEU115.N-VAL148.O 53.72
ARG105.NH2-PHE181.O 54.08
LYS88.N-SER81.O 54.45
SER267.OG-ASP263.O 54.81
ASN95.N-ASP33.O 55.17
SER123.N-ALA116.O 55.54
SER10.OG-GLU14.OE2 56.99
SER254.OG-ILE259.O 56.99
LEU167.N-VAL171.O 58.44
ARG131.NH2-ASP289.OD2 58.62
ARG40.NH2-ASP187.OD1 58.80
LEU89.N-VAL36.O 60.07
TYR37.N-LEU30.O 61.71
VAL20.N-LEU27.O 62.43
TYR182.OH-CYS160.O 62.98
GLY149.N-TYR161.O 63.34
VAL114.N-TYR126.O 67.70
VAL36.N-LEU89.O 69.87
HSE163.N-SER147.O 70.42
TRP31.N-CYS16.O 74.59
ARG40.NE-ASP187.OD2 77.50
B-chain – rep2
(continued)
LEU205.N-THR201.O 45.55
LEU75.N-VAL68.O 45.74
THR45.N-ASP48.OD1 45.92
THR201.OG1-GLU240.O 46.10
ASN231.N-LEU227.O 46.46
VAL157.N-LYS100.O 48.09
ILE78.N-LYS90.O 48.46
THR257.OG1-LEU253.O 49.18
GLY120.N-ASN28.OD1 50.45
TYR239.N-ALA234.O 50.64
LYS90.N-GLY79.O 51.91
GLN83.N-VAL86.O 52.09
GLY146.N-HSE163.O 52.09
THR21.N-LEU67.O 52.45
LEU115.N-VAL148.O 52.81
SER147.OG-SER144.O 53.72
SER254.OG-ILE259.O 55.17
ASN95.N-ASP33.O 55.35
LYS88.N-SER81.O 56.08
HSE172.N-ILE136.O 56.99
SER267.OG-ASP263.O 58.08
TYR37.N-LEU30.O 58.08
GLY109.N-MET130.O 58.62
GLY149.N-TYR161.O 58.80
SER123.N-ALA116.O 59.17
VAL20.N-LEU27.O 62.07
LEU167.N-VAL171.O 62.61
LEU89.N-VAL36.O 63.34
TYR182.OH-CYS160.O 64.61
ARG40.NE-ASP187.OD1 65.15
VAL114.N-TYR126.O 67.70
THR45.OG1-ASP48.OD1 68.24
VAL36.N-LEU89.O 68.78
ARG40.NH2-ASP187.OD2 72.41
HSE163.N-SER147.O 74.59
TRP31.N-CYS16.O 75.68
B-chain – rep3
Table 2.54 MD-HBs (with occupancy rates ≥30%) of the Mpro-delP168-and-a173v-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
2.4 Concluding Remarks 147
B-chain – rep1
GLY109.N-MET130.O 41.38
ARG131.NH2-ASP289.OD2 40.11
SER158.N-ASN151.O 37.57
LEU272.N-LEU268.O 37.57
LEU272.N-LEU268.O 37.21
LEU27.N-VAL20.O 37.21
ALA70.N-VAL73.O 35.75
LYS269.N-CYS265.O 35.39
CYS117.N-SER147.OG 35.03
ALA234.N-PHE230.O 36.48
CYS160.N-GLY149.O 36.48
ILE136.N-HSE172.O 36.12
THR292.OG1-ASP295.OD2 34.66 PHE159.N-LYS102.O 34.48
ALA255.N-GLY251.O 34.66
THR199.N-ASN238.O 35.57
ALA116.N-GLY124.O 35.57
ASN221.N-SER267.OG 35.57
THR21.N-LEU67.O 35.57
PHE159.N-LYS102.O 35.75
SER123.N-ALA116.O 38.48
LEU30.N-TYR37.O 36.12 SER158.N-ASN151.O 35.93 SER254.N-LEU250.O 35.57
ALA266.N-LEU262.O 37.02
SER10.OG-GLU14.OE2 36.84
HSD80.ND1-ASN63.OD1 36.12
SER158.N-ASN151.O 37.02
THR135.OG1-ASN133.OD1 38.84
SER158.N-ASN151.O 38.84
VAL18.N-GLY29.O 39.02
LEU272.N-LEU268.O 39.20
LEU27.N-VAL20.O 39.38
GLN83.N-VAL86.O 39.56
ARG105.NH1-ASP176.OD2 39.93
THR243.OG1-HSE246.ND1 40.11
ASN274.N-GLU270.O 40.11
LEU205.N-THR201.O 40.47
ALA234.N-PHE230.O 40.47
PHE150.N-SER113.O 40.47
VAL91.N-ASP34.O 40.65
THR175.OG1-ASP176.O 41.02
CYS160.N-GLY149.O 41.38
ILE200.N-ASP289.OD2 41.92
CYS128.N-PHE112.O 36.84
CYS160.N-GLY149.O 36.84
ALA70.N-VAL73.O 37.02
LYS269.N-CYS265.O 37.02
THR243.OG1-HSE246.ND1 37.75
LEU268.N-MET264.O 38.11
LEU27.N-VAL20.O 38.48
MET130.N-GLN110.O 38.66
ALA116.N-GLY124.O 38.66
ASN203.ND2-ASP289.O 38.84
ALA234.N-PHE230.O 39.02
PHE150.N-SER113.O 39.20
VAL173.N-MET165.O 39.38
ASN274.N-GLU270.O 39.75
ILE281.N-SER284.O 39.93
VAL91.N-ASP34.O 40.65
ASN180.N-ASP176.OD2 36.48
VAL173.N-MET165.O 37.02
THR21.N-LEU67.O 38.84
ALA234.N-PHE230.O 38.29
ALA116.N-GLY124.O 37.93
CYS128.N-PHE112.O 37.75
THR135.OG1-ASN133.OD1 39.02
VAL18.N-GLY29.O 38.84
SER301.OG-VAL297.O 38.66
MET130.N-GLN110.O 38.29
MET130.N-GLN110.O 39.56
TYR54.OH-ASP187.OD2 39.38
ASN203.ND2-ASP289.O 38.84
SER113.N-PHE150.O 38.66
GLN19.N-GLN69.O 40.11
SER144.OG-LEU141.O 39.75
SER254.N-LEU250.O 39.93
LEU87.N-CYS38.O 39.56
LEU268.N-MET264.O 41.02
GLY120.N-ASN28.OD1 40.29
ALA70.N-VAL73.O 40.29
THR21.N-LEU67.O 39.93
ILE136.N-HSE172.O 41.74
LEU75.N-VAL68.O 41.20
PHE150.N-SER113.O 41.38
VAL18.N-GLY29.O 40.29
ILE200.N-ASP289.OD2 42.29
PHE8.N-SER113.OG 42.11
SER144.OG-LEU141.O 41.56
THR175.OG1-ASP176.O 41.38
ALA70.N-VAL73.O 41.74
GLN83.N-VAL86.O 40.29
LEU205.N-THR201.O 42.65
SER254.N-LEU250.O 42.47
ARG131.NH2-ASP289.OD1 41.74
LEU268.N-MET264.O 43.01 GLN19.N-GLN69.O 42.29
PHE8.N-SER113.OG 41.56
VAL18.N-GLY29.O 41.92 LYS5.NZ-GLU290.OE1 41.92
THR175.OG1-ASP176.O 42.83
LEU67.N-THR21.O 42.65
ASN221.N-SER267.OG 42.83
GLN19.N-GLN69.O 42.47
LEU242.N-ASN231.OD1 43.74
PHE8.N-SER113.OG 43.74
LEU272.N-LEU268.O 42.29
GLY29.N-VAL18.O 42.29
ALA116.N-GLY124.O 43.92
LYS5.NZ-GLU290.OE2 43.01
LEU205.N-THR201.O 43.19
SER10.OG-GLU14.OE2 43.01
ILE136.N-HSE172.O 44.65 ASN231.N-LEU227.O 44.46 GLY29.N-VAL18.O 44.10
GLN19.N-GLN69.O 43.01 SER144.OG-LEU141.O 42.65 GLY120.N-ASN28.OD1 42.65
VAL91.N-ASP34.O 45.19
ARG131.NH1-ASP289.OD1 44.10
GLN69.N-GLN19.O 43.92
ASN180.N-ASP176.OD1 44.83
GLY29.N-VAL18.O 44.28
LEU268.N-MET264.O 44.46
A-chain – rep3 SER147.OG-SER144.O 43.38
VAL157.N-LYS100.O 43.56
A-chain – rep2
LEU242.N-ASN231.OD1 45.37
A-chain – rep1
VAL91.N-ASP34.O 44.65
Table 2.54 (continued) B-chain – rep2
ALA116.N-GLY124.O 36.66
SER254.N-LEU250.O 37.21
THR21.N-LEU67.O 37.21
CYS128.N-PHE112.O 37.39
ASN274.N-GLU270.O 37.39
ASN221.N-SER267.OG 37.57
CYS160.N-GLY149.O 37.75
GLN83.N-VAL86.O 37.93
LEU268.N-MET264.O 38.11
SER158.N-ASN151.O 38.29
LEU27.N-VAL20.O 38.48
LYS269.N-CYS265.O 38.66
ALA234.N-PHE230.O 38.84
LEU205.N-THR201.O 38.84
GLN69.N-GLN19.O 39.20
ALA70.N-VAL73.O 39.20
VAL91.N-ASP34.O 39.38
ASP153.N-CYS156.O 39.38
ASN203.ND2-ASP289.O 39.56
LEU272.N-LEU268.O 39.75
GLN19.N-GLN69.O 39.75
THR243.OG1-HSE246.ND1 40.11
VAL18.N-GLY29.O 40.47
GLY120.N-ASN28.OD1 41.38
PHE150.N-SER113.O 42.11
THR135.OG1-ASN133.OD1 42.11
MET162.N-THR175.O 42.29
VAL173.N-MET165.O 43.92
SER144.OG-LEU141.O 44.46
PHE8.N-SER113.OG 44.65
LEU75.N-VAL68.O 44.83
LEU242.N-ASN231.OD1 44.83
B-chain – rep3
CYS128.N-PHE112.O 34.85
LEU27.N-VAL20.O 35.39
ASN180.N-ASP176.OD2 35.75
LEU272.N-LEU268.O 35.75
SER158.N-ASN151.O 35.75
ASN221.N-SER267.OG 35.93
LYS61.NZ-ASP48.OD1 36.48
SER254.N-LEU250.O 36.48
GLN69.N-GLN19.O 36.48
THR243.OG1-HSE246.ND1 36.66
LYS269.N-CYS265.O 36.66
ASP153.N-CYS156.O 37.02
LEU268.N-MET264.O 37.75
CYS160.N-GLY149.O 37.75
MET162.N-THR175.O 38.11
TYR118.N-SER121.O 38.11
LEU67.N-THR21.O 38.29
LEU30.N-TYR37.O 38.84
VAL18.N-GLY29.O 39.02
ALA70.N-VAL73.O 39.20
PHE150.N-SER113.O 39.38
ASN274.N-GLU270.O 40.65
GLN19.N-GLN69.O 40.65
ARG105.NH2-PHE181.O 41.20
ALA116.N-GLY124.O 41.38
LEU242.N-ASN231.OD1 42.47
ALA234.N-PHE230.O 43.01
GLY29.N-VAL18.O 43.38
SER144.OG-LEU141.O 43.38
SER10.OG-GLU14.OE2 43.74
PHE8.N-SER113.OG 44.10
VAL91.N-ASP34.O 45.19
148 2 3C-Like Protease (3CLpro)
LYS269.N-CYS265.O 32.85 THR111.OG1-ASP295.OD2 32.85
GLN69.N-GLN19.O 32.85 THR135.OG1-ASN133.OD1 32.85 ALA266.N-LEU262.O 31.76 ASN180.N-ASP176.OD2 31.58 ILE200.N-ASP289.OD2 31.22 CYS265.N-VAL261.O 30.85
ASN180.N-ASP176.OD1 34.85
PHE159.N-LYS102.O 34.48
ASN203.ND2-ASP289.O 34.48
LEU27.N-VAL20.O 34.30
SER113.N-PHE150.O 34.30
THR243.OG1-HSE246.ND1 34.30
THR199.N-ASN238.O 34.12
SER113.OG-GLN127.OE1 34.12
CYS128.N-PHE112.O 33.76
ALA255.N-GLY251.O 33.39
THR21.OG1-THR25.O 33.03
ARG298.N-PHE294.O 34.85
PHE159.N-LYS102.O 34.48
ARG105.NH1-ASP176.OD1 34.30
ALA255.N-GLY251.O 33.58
GLN299.N-ASP295.O 33.39
LYS269.N-CYS265.O 33.21
ALA266.N-LEU262.O 33.03
CYS38.N-LEU87.O 32.85
GLN69.N-GLN19.O 32.85
GLN256.N-PRO252.O 30.13
ASN221.N-SER267.OG 30.31
SER62.N-ASN65.OD1 30.31
LYS5.NZ-GLU288.OE1 30.31
LYS5.NZ-GLU290.OE1 30.13
ASN180.N-ASP176.OD1 30.13
GLN83.N-VAL86.O 30.85
PHE112.N-CYS128.O 30.67
CYS117.N-SER147.OG 30.67
ASN203.ND2-GLY109.O 30.13
ASN203.ND2-ASP289.O 30.49
TYR209.OH-ILE259.O 32.12
SER81.N-LYS88.O 31.03
LEU57.N-ASN53.O 31.40
TYR209.OH-ILE259.O 31.03
ALA255.N-GLY251.O 32.12
THR292.N-ASP295.OD2 30.31
VAL173.N-MET165.O 30.85 TYR209.OH-ILE259.O 30.49
ASN221.N-SER267.OG 30.85
ILE281.N-SER284.O 32.67
CYS265.N-VAL261.O 32.67
LEU30.N-TYR37.O 32.30
TYR118.N-SER121.O 32.30
ASN133.ND2-GLY195.O 32.12
GLN69.N-GLN19.O 32.12
CYS265.N-VAL261.O 32.49
PHE112.N-CYS128.O 32.49
ARG298.NH2-ASP295.OD1 33.03
CYS128.N-PHE112.O 33.03
THR292.OG1-ASP295.OD2 34.30
ILE281.N-SER284.O 34.30
SER254.N-LEU250.O 34.66
LEU30.N-TYR37.O 34.85
CYS265.N-VAL261.O 31.94
TYR118.N-SER121.O 33.03
PHE112.N-CYS128.O 33.21
TYR209.OH-ILE259.O 33.39
CYS38.N-LEU87.O 33.39
SER10.OG-GLU14.OE1 33.58
THR21.N-LEU67.O 33.76
ALA266.N-LEU262.O 34.85
THR292.OG1-ASP295.OD1 35.03
MET130.N-GLN110.O 35.21
THR135.OG1-ASN133.OD1 35.03
SER113.N-PHE150.O 33.94
CYS160.N-GLY149.O 35.03
ILE200.N-ASP289.OD1 35.39
SER10.OG-GLU14.OE2 34.12
PHE150.N-SER113.O 35.03
THR243.OG1-HSE246.ND1 35.75
ARG105.NH1-ASP176.OD2 30.31
ASN180.N-ASP176.OD1 30.67
CYS38.N-LEU87.O 31.03
PHE159.N-LYS102.O 31.40
PHE112.N-CYS128.O 31.58
LYS5.NZ-GLU290.OE1 31.76
ALA255.N-GLY251.O 31.76
ASN180.N-ASP176.OD2 32.12
VAL104.N-PHE159.O 32.30
TYR209.OH-ILE259.O 32.49
ASN133.ND2-GLY195.O 32.85
GLN256.N-PRO252.O 33.21
THR21.OG1-THR25.O 33.76
CYS265.N-VAL261.O 33.94
LEU30.N-TYR37.O 34.12
MET130.N-GLN110.O 34.30
THR292.OG1-ASP295.OD2 34.66
THR175.OG1-ASP176.O 35.93
ILE200.N-ASP289.OD2 36.66
VAL173.N-MET165.O 30.31
THR292.OG1-ASP295.OD1 30.31
TYR126.N-VAL114.O 30.31
LYS5.NZ-GLU290.OE1 30.49
LEU87.N-CYS38.O 31.22
ALA266.N-LEU262.O 31.40
THR175.OG1-ASP176.O 31.40
ALA255.N-GLY251.O 31.40
CYS38.N-LEU87.O 32.12
LEU208.N-VAL204.O 32.30
ASN203.ND2-ASP289.O 32.67
ILE136.N-HSE172.O 32.85
ILE281.N-SER284.O 33.21
LYS5.NZ-GLU290.OE2 33.39
PHE112.N-CYS128.O 33.76
THR135.OG1-ASN133.OD1 34.12
CYS265.N-VAL261.O 34.66
2.4 Concluding Remarks 149
ARG131.NH2-ASP289.OD2 64.79
LEU167.N-VAL171.O 62.61
SER267.OG-ASP263.O 64.97
TYR182.OH-CYS160.O 62.79
LEU167.N-VAL171.O 61.71
ASN95.N-ASP33.O 60.25
GLY146.N-HSE163.O 59.89
GLY109.N-MET130.O 59.35
TYR37.N-LEU30.O 58.62
GLY149.N-TYR161.O 58.44
VAL20.N-LEU27.O 57.53
LEU89.N-VAL36.O 57.17
LEU115.N-VAL148.O 56.99
SER123.N-ALA116.O 56.26
THR21.N-LEU67.O 55.35
SER254.OG-ILE259.O 54.26
ARG105.NH2-PHE181.O 53.72
TYR37.N-LEU30.O 62.98
VAL36.N-LEU89.O 62.43
TYR182.OH-CYS160.O 62.25
ASN95.N-ASP33.O 61.16
GLY149.N-TYR161.O 59.53
LEU89.N-VAL36.O 59.17
VAL20.N-LEU27.O 59.17
THR257.OG1-LEU253.O 59.17
ARG105.NH2-PHE181.O 58.26
SER254.OG-ILE259.O 58.26
SER147.OG-SER144.O 57.89
GLY146.N-HSE163.O 57.71
SER267.OG-ASP263.O 56.08
LEU87.N-CYS38.O 56.08
ARG131.NH2-ASP289.OD2 55.72
LYS88.N-SER81.O 54.45
LEU75.N-VAL68.O 52.27
VAL157.N-LYS100.O 51.54
TYR239.N-ALA234.O 51.36
VAL91.N-ASP34.O 50.82
GLY120.N-ASN28.OD1 49.00
ARG131.NH2-ASP289.OD2 49.00
ILE78.N-LYS90.O 48.82
GLN83.N-VAL86.O 47.73
LEU242.N-ASN231.OD1 47.19
SER147.OG-SER144.O 45.92
HSE172.N-ILE136.O 45.92
ALA116.N-GLY124.O 45.37
ASN231.N-LEU227.O 45.19
GLY29.N-VAL18.O 45.01
PHE8.N-SER113.OG 44.46
LEU115.N-VAL148.O 52.45
SER10.OG-GLU14.OE2 50.45
LYS90.N-GLY79.O 50.27
LEU75.N-VAL68.O 49.91
GLY109.N-MET130.O 49.55
ASN231.N-LEU227.O 49.55
THR21.N-LEU67.O 48.09
VAL157.N-LYS100.O 48.09
THR201.OG1-GLU240.O 47.55
TYR239.N-ALA234.O 46.64
GLY120.N-ASN28.OD1 46.64
GLY29.N-VAL18.O 46.28
ALA173.N-MET165.O 46.28
THR175.OG1-ASP176.O 46.28
TYR118.N-SER121.O 45.92
LEU242.N-ASN231.OD1 45.37
PHE8.N-SER113.OG 46.64
VAL18.N-GLY29.O 45.37
THR175.OG1-ASP176.O 45.74
ARG40.NE-ASP187.OD1 46.82 CYS160.N-GLY149.O 45.92
SER144.OG-LEU141.O 45.74
LEU67.N-THR21.O 46.10
VAL91.N-ASP34.O 47.01 TYR239.N-ALA234.O 47.01
PHE8.N-SER113.OG 46.46
ARG105.NH1-ASP176.OD1 47.01
LEU75.N-VAL68.O 46.64
THR201.OG1-GLU240.O 47.55
ASN231.N-LEU227.O 46.64
GLY29.N-VAL18.O 46.82
THR175.OG1-ASP176.O 47.73 THR21.N-LEU67.O 47.55
TYR239.N-ALA234.O 47.37
ILE78.N-LYS90.O 48.09
LYS90.N-GLY79.O 50.09 LEU75.N-VAL68.O 49.73
GLY109.N-MET130.O 49.73
ASN180.N-ASP176.OD2 50.09
SER147.OG-SER144.O 50.27
VAL157.N-LYS100.O 51.36
THR257.OG1-LEU253.O 51.91
LYS88.N-SER81.O 52.27
SER123.N-ALA116.O 53.54 LEU115.N-VAL148.O 50.64
SER123.N-ALA116.O 52.27
ARG105.NH2-PHE181.O 53.36
THR257.OG1-LEU253.O 52.45
ARG40.NH2-ASP187.OD2 53.54
LYS88.N-SER81.O 50.64
HSE172.N-ILE136.O 52.81
ARG60.NH2-ASP48.OD1 53.54
LYS90.N-GLY79.O 52.63
VAL157.N-LYS100.O 50.82
THR257.OG1-LEU253.O 53.36
ASN231.N-LEU227.O 53.90
LYS88.N-SER81.O 51.18
ARG105.NH2-PHE181.O 53.90
THR45.N-ASP48.OD2 54.63
GLY109.N-MET130.O 51.72
LEU89.N-VAL36.O 54.99
LEU89.N-VAL36.O 54.99
LYS90.N-GLY79.O 54.99
VAL20.N-LEU27.O 55.90
SER10.OG-GLU14.OE2 57.53
SER254.OG-ILE259.O 58.26 GLY149.N-TYR161.O 56.08
GLY146.N-HSE163.O 57.71
LEU115.N-VAL148.O 58.08
ASN95.N-ASP33.O 59.17
TYR37.N-LEU30.O 60.25
THR45.OG1-ASP48.OD2 59.53 GLY146.N-HSE163.O 59.17
VAL20.N-LEU27.O 61.71
SER147.OG-SER144.O 60.44 SER123.N-ALA116.O 59.35
SER254.OG-ILE259.O 63.16
GLY149.N-TYR161.O 61.16
LEU167.N-VAL171.O 63.88
TYR182.OH-CYS160.O 65.15
TYR182.OH-CYS160.O 64.97
TRP31.N-CYS16.O 71.51
TYR54.OH-ASP187.OD1 63.16
ASN95.N-ASP33.O 61.34
VAL36.N-LEU89.O 68.24
VAL36.N-LEU89.O 66.24
ARG40.NH2-ASP187.OD1 71.51
LEU167.N-VAL171.O 63.88
SER267.OG-ASP263.O 64.43
ARG40.NH2-ASP187.OD2 68.78
HSE163.N-SER147.O 66.61
VAL114.N-TYR126.O 71.69
VAL114.N-TYR126.O 67.15
TYR37.N-LEU30.O 61.52
HSE163.N-SER147.O 70.96
SER267.OG-ASP263.O 67.15
HSE163.N-SER147.O 71.87
TRP31.N-CYS16.O 71.32
VAL114.N-TYR126.O 64.79
TRP31.N-CYS16.O 72.60
VAL114.N-TYR126.O 72.60
VAL36.N-LEU89.O 72.05
HSE163.N-SER147.O 72.96
SER10.OG-GLU14.OE2 62.07
ARG40.NE-ASP187.OD1 81.67
TRP31.N-CYS16.O 73.87
ARG40.NE-ASP187.OD2 74.77
ARG40.NE-ASP187.OD1 77.13
B-chain – rep1
A-chain – rep3
A-chain – rep2
A-chain – rep1
LEU242.N-ASN231.OD1 45.01
PHE8.N-SER113.OG 45.01
ARG131.NH1-ASP289.OD1 45.19
VAL91.N-ASP34.O 45.37
THR257.OG1-LEU253.O 47.01
LEU67.N-THR21.O 47.19
LYS88.N-SER81.O 47.55
SER147.OG-SER144.O 47.91
ARG40.NH2-ASP187.OD1 47.91
ASN180.N-ASP176.OD1 48.82
ASN231.N-LEU227.O 49.55
TYR239.N-ALA234.O 50.82
THR201.OG1-GLU240.O 51.00
ILE78.N-LYS90.O 51.72
LEU75.N-VAL68.O 52.27
SER123.N-ALA116.O 52.81
LYS90.N-GLY79.O 53.18
LEU115.N-VAL148.O 53.36
HSE172.N-ILE136.O 53.72
VAL157.N-LYS100.O 54.26
SER254.OG-ILE259.O 54.45
GLY109.N-MET130.O 54.45
LEU89.N-VAL36.O 55.54
TYR37.N-LEU30.O 56.99
ARG105.NH2-PHE181.O 57.53
ARG40.NE-ASP187.OD2 57.71
GLY146.N-HSE163.O 58.98
VAL20.N-LEU27.O 59.35
SER267.OG-ASP263.O 59.35
TYR182.OH-CYS160.O 59.89
ASN95.N-ASP33.O 60.25
ARG131.NH2-ASP289.OD2 62.25
SER10.OG-GLU14.OE2 63.70
LEU167.N-VAL171.O 66.97
GLY149.N-TYR161.O 67.15
VAL36.N-LEU89.O 67.70
VAL114.N-TYR126.O 68.78
HSE163.N-SER147.O 73.87
TRP31.N-CYS16.O 74.05
B-chain – rep2
ILE136.N-HSE172.O 43.74
ARG40.NE-ASP187.OD2 43.92
ARG40.NH2-ASP187.OD1 44.83
GLY109.N-MET130.O 45.19
LEU242.N-ASN231.OD1 45.37
THR175.OG1-ASP176.O 45.37
HSE172.N-ILE136.O 45.92
PHE150.N-SER113.O 45.92
GLY120.N-ASN28.OD1 46.82
LEU75.N-VAL68.O 46.82
TYR239.N-ALA234.O 47.37
THR21.N-LEU67.O 48.09
ILE78.N-LYS90.O 49.18
THR201.OG1-GLU240.O 49.18
LYS90.N-GLY79.O 49.36
ASN231.N-LEU227.O 49.55
ARG131.NH2-ASP289.OD1 49.91
THR257.OG1-LEU253.O 50.45
PHE8.N-SER113.OG 50.82
VAL157.N-LYS100.O 51.54
LYS88.N-SER81.O 52.63
ARG105.NH2-PHE181.O 53.36
ASN95.N-ASP33.O 55.17
GLY146.N-HSE163.O 56.08
SER147.OG-SER144.O 57.35
SER254.OG-ILE259.O 57.71
LEU115.N-VAL148.O 57.71
TYR37.N-LEU30.O 58.80
SER123.N-ALA116.O 59.17
VAL20.N-LEU27.O 59.71
SER267.OG-ASP263.O 59.71
LEU89.N-VAL36.O 59.89
LEU167.N-VAL171.O 62.07
TYR182.OH-CYS160.O 62.07
GLY149.N-TYR161.O 65.70
HSE163.N-SER147.O 65.88
TRP31.N-CYS16.O 70.24
VAL36.N-LEU89.O 71.69
VAL114.N-TYR126.O 71.69
B-chain – rep3
Table 2.55 MD-HBs (with occupancy rates ≥30%) of the Mpro-delP168-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
150 2 3C-Like Protease (3CLpro)
ALA234.N-PHE230.O 44.83
SER144.OG-LEU141.O 41.02
LEU67.N-THR21.O 36.84
CYS38.N-LEU87.O 36.84
ASN274.N-GLU270.O 39.02
LEU205.N-THR201.O 38.66
ALA266.N-LEU262.O 34.48
SER254.N-LEU250.O 34.12
TYR182.N-GLY174.O 33.94
PHE112.N-CYS128.O 36.84
ALA70.N-VAL73.O 35.93
MET130.N-GLN110.O 35.21
SER10.OG-GLU14.OE1 35.03
LEU87.N-CYS38.O 34.85
ARG131.NH1-ASP289.OD1 37.39
GLN83.N-VAL86.O 37.21
ILE136.N-HSE172.O 35.75
LEU87.N-CYS38.O 35.75
TYR209.OH-ILE259.O 36.48 ASN203.ND2-ASP289.O 35.75
ASN221.N-SER267.OG 36.30 ALA234.N-PHE230.O 35.93
ARG105.NH1-ASP176.OD2 36.48 THR21.N-LEU67.O 36.48
ALA266.N-LEU262.O 36.48 ALA255.N-GLY251.O 36.30
LEU27.N-VAL20.O 37.02 ILE200.N-ASP289.OD2 36.66 MET130.N-GLN110.O 36.66
LEU27.N-VAL20.O 37.57 LEU272.N-LEU268.O 37.21 LEU30.N-TYR37.O 36.66
LEU205.N-THR201.O 35.57
TYR209.OH-ILE259.O 35.39
GLN69.N-GLN19.O 35.21
ASN221.N-SER267.OG 37.75
CYS128.N-PHE112.O 37.75
SER144.OG-LEU141.O 37.57
GLN19.N-GLN69.O 37.39 THR243.OG1-HSE246.ND1 37.21
ASN203.ND2-ASP289.O 37.75
LEU272.N-LEU268.O 37.57
ARG60.NH1-ASP56.OD1 38.48
ASN221.N-SER267.OG 35.93
THR243.OG1-HSE246.ND1 38.11 ASP153.N-CYS156.O 37.75
ALA234.N-PHE230.O 37.93
SER254.N-LEU250.O 38.66
MET130.N-GLN110.O 36.30
ASN180.N-ASP176.OD1 38.48
ASN203.ND2-ASP289.O 35.75
CYS160.N-GLY149.O 37.93
TYR118.N-SER121.O 39.20
THR243.OG1-HSE246.ND1 36.30
CYS160.N-GLY149.O 38.66
PHE159.N-LYS102.O 35.57
SER158.N-ASN151.O 37.93
ALA70.N-VAL73.O 39.56
CYS128.N-PHE112.O 36.66
TYR209.OH-ILE259.O 37.93
THR135.OG1-ASN133.OD1 38.11
LEU67.N-THR21.O 39.75
ALA234.N-PHE230.O 37.93
GLN69.N-GLN19.O 38.66
VAL18.N-GLY29.O 40.29
SER254.N-LEU250.O 38.84
SER158.N-ASN151.O 39.02
ASN221.N-SER267.OG 39.20
LEU272.N-LEU268.O 37.93
LEU27.N-VAL20.O 39.20
ILE200.N-ASP289.OD2 41.38
ASN180.N-ASP176.OD1 38.11
LEU272.N-LEU268.O 39.20 ALA173.N-MET165.O 41.92
MET162.N-THR175.O 40.11 CYS128.N-PHE112.O 40.11 LEU87.N-CYS38.O 39.56
ALA116.N-GLY124.O 42.47 ARG40.NH2-ASP187.OD2 42.47 LEU242.N-ASN231.OD1 42.11
ALA70.N-VAL73.O 39.38
ALA173.N-MET165.O 38.84
ALA234.N-PHE230.O 38.66
SER254.N-LEU250.O 39.20
ARG105.NH1-ASP176.OD2 39.20
VAL18.N-GLY29.O 39.38
LEU268.N-MET264.O 41.38
ALA116.N-GLY124.O 40.65 ASN274.N-GLU270.O 40.65
GLN19.N-GLN69.O 42.83 GLY120.N-ASN28.OD1 42.65
THR201.OG1-GLU240.O 39.38
LEU30.N-TYR37.O 39.38
GLN19.N-GLN69.O 40.83
ALA116.N-GLY124.O 39.56
LEU268.N-MET264.O 41.02 GLN83.N-VAL86.O 41.02
CYS128.N-PHE112.O 42.83 ASN274.N-GLU270.O 42.83
GLN19.N-GLN69.O 40.47
LEU27.N-VAL20.O 39.56
LEU268.N-MET264.O 41.56
ILE200.N-ASP289.OD2 41.02
CYS128.N-PHE112.O 42.29
MET130.N-GLN110.O 34.85
GLN69.N-GLN19.O 35.75
ASN203.ND2-ASP289.O 36.30
ARG131.N-THR135.O 36.48
LEU27.N-VAL20.O 36.66
ASP153.N-CYS156.O 36.84
LYS269.N-CYS265.O 37.02
ALA70.N-VAL73.O 37.21
SER254.N-LEU250.O 37.75
SER158.N-ASN151.O 37.93
ILE200.N-ASP289.OD2 38.29
THR135.OG1-ASN133.OD1 38.84
ILE136.N-HSE172.O 39.02
GLN19.N-GLN69.O 39.38
VAL18.N-GLY29.O 39.56
TYR182.N-GLY174.O 40.11
CYS38.N-LEU87.O 40.29
GLN83.N-VAL86.O 40.65
THR175.OG1-ASP176.O 40.83
ASN274.N-GLU270.O 41.02
ALA116.N-GLY124.O 41.92
CYS160.N-GLY149.O 41.92
PHE150.N-SER113.O 42.29
LEU272.N-LEU268.O 42.29
THR45.OG1-ASP48.OD1 41.20 PHE150.N-SER113.O 41.20
ILE78.N-LYS90.O 44.28 LEU205.N-THR201.O 43.38
PHE150.N-SER113.O 42.11
LEU268.N-MET264.O 42.11
LEU67.N-THR21.O 42.11
ILE136.N-HSE172.O 41.56
GLY120.N-ASN28.OD1 43.74 MET162.N-THR175.O 42.83
GLY120.N-ASN28.OD1 42.11 VAL91.N-ASP34.O 41.38
MET162.N-THR175.O 44.83 PHE150.N-SER113.O 44.65
VAL18.N-GLY29.O 43.01
MET162.N-THR175.O 42.83
GLY29.N-VAL18.O 43.74
LEU205.N-THR201.O 44.10
ARG105.NH1-ASP176.OD2 44.46
THR21.N-LEU67.O 44.65
VAL91.N-ASP34.O 43.01
THR201.OG1-GLU240.O 43.56 ASN180.N-ASP176.OD1 43.01 ARG131.NH1-ASP289.OD1 42.65
ARG131.NH2-ASP289.OD2 45.37 LEU268.N-MET264.O 45.37 GLN83.N-VAL86.O 45.19
TYR54.OH-ASP187.O 44.65 LEU205.N-THR201.O 43.56
HSE172.N-ILE136.O 45.74 GLY29.N-VAL18.O 45.55
LEU242.N-ASN231.OD1 42.83
SER144.OG-LEU141.O 43.56
ILE200.N-ASP289.OD2 43.38
ASN274.N-GLU270.O 43.38
PHE8.N-SER113.OG 44.46
MET162.N-THR175.O 43.92
HSE172.N-ILE136.O 44.65
ILE78.N-LYS90.O 43.56
CYS160.N-GLY149.O 44.10
THR175.OG1-ASP176.O 44.10
PHE150.N-SER113.O 45.37
LEU205.N-THR201.O 43.56
(continued)
LYS269.N-CYS265.O 34.12
TYR209.OH-ILE259.O 35.21
ALA255.N-GLY251.O 35.21
MET130.N-GLN110.O 35.57
CYS160.N-GLY149.O 35.93
ALA70.N-VAL73.O 36.12
SER113.N-PHE150.O 36.48
ARG131.NH1-ASP289.OD2 36.66
SER158.N-ASN151.O 36.66
THR243.OG1-HSE246.ND1 37.21
LEU268.N-MET264.O 37.57
ASN221.N-SER267.OG 37.75
GLN69.N-GLN19.O 37.75
LEU30.N-TYR37.O 37.75
THR292.OG1-ASP295.OD1 38.11
ALA234.N-PHE230.O 38.11
THR135.OG1-ASN133.OD1 38.11
LEU27.N-VAL20.O 38.48
TYR118.N-SER121.O 38.84
GLY29.N-VAL18.O 39.02
LEU272.N-LEU268.O 39.02
GLN19.N-GLN69.O 39.38
ASN274.N-GLU270.O 40.29
SER10.OG-GLU14.OE1 40.65
MET162.N-THR175.O 40.65
VAL18.N-GLY29.O 40.65
CYS128.N-PHE112.O 40.83
LEU67.N-THR21.O 40.83
LEU87.N-CYS38.O 41.02
ASP153.N-CYS156.O 41.74
VAL91.N-ASP34.O 41.92
ALA116.N-GLY124.O 42.11
GLN83.N-VAL86.O 43.01
2.4 Concluding Remarks 151
PHE159.N-LYS102.O 34.66
LYS5.NZ-GLU290.OE1 31.22
CYS265.N-VAL261.O 31.22
GLN256.N-PRO252.O 30.85
THR292.OG1-ASP295.OD2 30.85
ALA255.N-GLY251.O 30.67
ASN133.ND2-GLY195.O 30.49
CYS117.N-SER147.OG 30.49
LYS5.NZ-GLU290.OE1 32.49
SER267.N-ASP263.O 32.30
LYS269.N-CYS265.O 31.76
ARG4.N-GLN299.OE1 31.58
VAL104.N-PHE159.O 31.40
ASN133.ND2-GLY195.O 30.49
THR199.N-ASN238.O 30.31
GLN256.N-PRO252.O 30.31
MET235.N-ASN231.O 31.22
ARG188.NH1-GLU55.OE2 30.49 ARG188.NH1-GLU55.OE1 30.49 SER81.N-LYS88.O 30.13
THR292.OG1-ASP295.OD2 31.03 LYS5.NZ-GLU290.OE2 30.49 ALA211.N-TRP207.O 30.49 ILE281.N-SER284.O 30.13
THR21.OG1-THR25.O 30.49
TYR118.N-SER121.O 30.85
ASN133.ND2-GLY195.O 31.03
ALA255.N-GLY251.O 31.22
GLN256.N-PRO252.O 31.58
CYS265.N-VAL261.O 31.94
LYS269.N-CYS265.O 32.12
ILE281.N-SER284.O 32.30
GLN256.N-PRO252.O 31.40
ILE136.N-HSE172.O 31.94
ARG60.NH1-ASP56.OD2 32.30
CYS265.N-VAL261.O 32.49
PHE112.N-CYS128.O 32.49
TYR209.OH-ILE259.O 33.39
SER144.OG-LEU141.O 33.39
THR135.OG1-ASN133.OD1 33.94
ALA266.N-LEU262.O 32.85
ALA173.N-MET165.O 33.76
SER158.N-ASN151.O 34.30
LYS5.NZ-GLU290.OE2 31.40
GLN69.N-GLN19.O 32.85
THR135.OG1-ASN133.OD1 32.49 THR243.OG1-HSE246.ND1 33.94
ASP153.N-CYS156.O 34.30 LYS5.NZ-GLU290.OE1 34.12 PHE112.N-CYS128.O 33.94
ASN133.ND2-GLY195.O 34.85 TYR182.N-GLY174.O 34.66 VAL104.N-PHE159.O 34.48
THR135.OG1-ASN133.OD1 32.85
ILE136.N-HSE172.O 31.58
ASN180.N-ASP176.OD2 31.40
LEU30.N-TYR37.O 34.48
PHE159.N-LYS102.O 33.39
THR292.OG1-ASP295.OD1 33.76
GLN69.N-GLN19.O 35.57 MET130.N-GLN110.O 35.03
B-chain – rep1 ALA70.N-VAL73.O 35.57
ALA266.N-LEU262.O 33.03
PHE112.N-CYS128.O 33.76
TYR118.N-SER121.O 33.03
ALA255.N-GLY251.O 34.66
LEU30.N-TYR37.O 34.48
A-chain – rep3 PHE159.N-LYS102.O 35.75
A-chain – rep2
SER158.N-ASN151.O 33.94
A-chain – rep1
ASN203.ND2-ASP289.O 34.85
Table 2.55 (continued) B-chain – rep2
THR243.OG1-HSE246.ND1 31.03
LEU30.N-TYR37.O 31.40
ALA255.N-GLY251.O 31.76
LYS5.NZ-GLU288.OE1 31.94
PHE112.N-CYS128.O 32.67
LYS5.NZ-GLU290.OE1 33.39
THR199.N-ASN238.O 33.39
ALA173.N-MET165.O 34.12
ILE281.N-SER284.O 34.12
CYS265.N-VAL261.O 34.12
PHE159.N-LYS102.O 34.30
ASN221.N-SER267.OG 34.30
B-chain – rep3
CYS38.N-LEU87.O 30.67
THR199.N-ASN238.O 30.85
ASN180.N-ASP176.OD2 31.22
LYS5.NZ-GLU288.OE1 31.22
ILE200.N-ASP289.OD1 31.76
LYS5.NZ-GLU290.OE2 32.49
ASN180.N-ASP176.OD1 32.49
LYS5.NZ-GLU290.OE1 32.67
SER254.N-LEU250.O 32.67
PHE112.N-CYS128.O 33.03
PHE159.N-LYS102.O 33.39
TYR182.N-GLY174.O 33.58
ALA266.N-LEU262.O 33.76
ASN203.ND2-ASP289.O 33.94
ALA173.N-MET165.O 33.94
152 2 3C-Like Protease (3CLpro)
TYR182.OH-CYS160.O 62.79 SER267.OG-ASP263.O 62.25 GLY149.N-TYR161.O 61.34
VAL20.N-LEU27.O 62.98 TYR37.N-LEU30.O 62.07
VAL20.N-LEU27.O 60.80
SER123.N-ALA116.O 59.35
SER254.OG-ILE259.O 62.07
LEU272.N-LEU268.O 46.64 MET162.N-THR175.O 46.46
MET162.N-THR175.O 45.92
LEU87.N-CYS38.O 47.01 GLY120.N-ASN28.OD1 46.82
THR135.OG1-ASN133.OD1 46.82 LEU242.N-ASN231.OD1 46.82
TYR239.N-ALA234.O 48.28 ILE78.N-LYS90.O 47.73 ASN231.N-LEU227.O 47.55
SER10.OG-GLU14.OE2 47.73 ARG40.NH2-ASP187.OD1 46.82
LEU268.N-MET264.O 46.82
GLY146.N-HSE163.O 45.74
LEU67.N-THR21.O 48.46
THR201.OG1-GLU240.O 48.09
THR201.OG1-GLU240.O 47.01
LYS88.N-SER81.O 49.73
ILE78.N-LYS90.O 48.82
GLY109.N-MET130.O 48.64
LYS90.N-GLY79.O 48.64
PHE8.N-SER113.OG 46.82
ILE78.N-LYS90.O 50.27
VAL157.N-LYS100.O 49.55
LYS90.N-GLY79.O 49.00
ALA116.N-GLY124.O 49.18
HSE172.N-ILE136.O 45.92
VAL157.N-LYS100.O 50.45
LEU67.N-THR21.O 49.91
SER144.OG-LEU141.O 49.18
TYR239.N-ALA234.O 50.09
LEU268.N-MET264.O 45.37
GLY109.N-MET130.O 50.82
LYS90.N-GLY79.O 50.27
ARG105.NH2-PHE181.O 50.82
ILE78.N-LYS90.O 51.00
ARG105.NH2-PHE181.O 47.19
ASN231.N-LEU227.O 51.36
LEU87.N-CYS38.O 51.00
THR257.OG1-LEU253.O 51.36
GLY109.N-MET130.O 51.91
HSE172.N-ILE136.O 47.19
THR257.OG1-LEU253.O 51.72
ASN231.N-LEU227.O 51.54
SER123.N-ALA116.O 52.27
VAL157.N-LYS100.O 51.91
SER147.OG-SER144.O 47.55
GLY120.N-ASN28.OD1 51.91
SER123.N-ALA116.O 51.54
VAL157.N-LYS100.O 52.99
ARG105.NH2-PHE181.O 52.09
THR21.N-LEU67.O 46.46
LYS90.N-GLY79.O 51.91
GLY146.N-HSE163.O 51.54
ARG131.NH1-ASP289.OD1 53.72
THR257.OG1-LEU253.O 52.63
LEU75.N-VAL68.O 48.64
THR21.N-LEU67.O 52.63
THR257.OG1-LEU253.O 52.63
GLY146.N-HSE163.O 54.63
SER147.OG-SER144.O 53.18
LEU242.N-ASN231.OD1 48.46
LEU89.N-VAL36.O 54.63
GLY109.N-MET130.O 52.99
VAL20.N-LEU27.O 54.81
HSE172.N-ILE136.O 55.35
ARG40.NE-ASP187.OD2 53.90
SER123.N-ALA116.O 53.90
TYR239.N-ALA234.O 47.55
GLY146.N-HSE163.O 55.54
LEU115.N-VAL148.O 53.54
THR201.OG1-GLU240.O 48.64
SER10.OG-GLU14.OE2 56.26
LYS88.N-SER81.O 54.81
LYS88.N-SER81.O 56.08
ASN95.N-ASP33.O 54.63
TYR37.N-LEU30.O 58.26
GLY120.N-ASN28.OD1 48.46
ASN95.N-ASP33.O 56.26
VAL20.N-LEU27.O 57.17
LEU115.N-VAL148.O 56.99
TYR239.N-ALA234.O 48.09
TYR37.N-LEU30.O 56.44
ASN95.N-ASP33.O 57.35
LEU89.N-VAL36.O 58.44
SER254.OG-ILE259.O 57.71
LEU115.N-VAL148.O 56.62
ASN95.N-ASP33.O 58.62
LEU167.N-VAL171.O 58.08
TYR182.OH-CYS160.O 58.08
LEU115.N-VAL148.O 58.80
ARG131.NH2-ASP289.OD2 58.62
SER147.OG-SER144.O 58.08
LEU167.N-VAL171.O 57.53
SER10.OG-GLU14.OE1 58.62
LEU89.N-VAL36.O 58.44
SER254.OG-ILE259.O 59.17
SER267.OG-ASP263.O 60.80 LEU89.N-VAL36.O 59.17
TYR182.OH-CYS160.O 58.26
SER254.OG-ILE259.O 58.08
TYR37.N-LEU30.O 60.07
GLY149.N-TYR161.O 59.35
LEU167.N-VAL171.O 65.88
SER267.OG-ASP263.O 60.44
HSE163.N-SER147.O 71.69 VAL114.N-TYR126.O 70.24
VAL114.N-TYR126.O 66.42 GLY149.N-TYR161.O 65.15 TYR182.OH-CYS160.O 63.70
GLY149.N-TYR161.O 64.79
HSE163.N-SER147.O 62.98
SER267.OG-ASP263.O 62.98
VAL114.N-TYR126.O 66.61
ARG131.NH2-ASP289.OD2 64.07
VAL36.N-LEU89.O 73.32 TRP31.N-CYS16.O 72.05
VAL36.N-LEU89.O 70.78 TRP31.N-CYS16.O 67.51
VAL114.N-TYR126.O 67.70
VAL36.N-LEU89.O 66.61
VAL36.N-LEU89.O 71.32
TRP31.N-CYS16.O 71.14
LEU167.N-VAL171.O 62.98
B-chain – rep1 ARG131.NH2-ASP289.OD2 74.05
A-chain – rep3 HSE163.N-SER147.O 72.23
A-chain – rep2
TRP31.N-CYS16.O 74.95
A-chain – rep1
HSE163.N-SER147.O 72.23
ILE78.N-LYS90.O 44.46
MET162.N-THR175.O 45.19
ASN231.N-LEU227.O 46.10
GLN83.N-VAL86.O 47.01
GLY29.N-VAL18.O 47.01
SER123.N-ALA116.O 47.91
ARG105.NH2-PHE181.O 49.73
VAL157.N-LYS100.O 49.73
SER147.OG-SER144.O 50.45
TYR239.N-ALA234.O 50.82
THR257.OG1-LEU253.O 51.00
LYS90.N-GLY79.O 51.54
HSE172.N-ILE136.O 51.54
GLY109.N-MET130.O 51.72
LYS88.N-SER81.O 52.27
LEU115.N-VAL148.O 52.27
PHE8.N-SER113.OG 52.45
ARG40.NE-ASP187.OD2 57.53
ASN95.N-ASP33.O 57.71
GLY146.N-HSE163.O 58.26
LEU167.N-VAL171.O 58.80
ARG40.NH2-ASP187.OD1 58.80
GLY149.N-TYR161.O 58.80
TYR37.N-LEU30.O 59.17
SER254.OG-ILE259.O 60.07
VAL20.N-LEU27.O 60.44
ARG131.NH2-ASP289.OD2 61.34
LEU89.N-VAL36.O 62.25
TYR182.OH-CYS160.O 62.43
SER267.OG-ASP263.O 63.70
VAL114.N-TYR126.O 70.05
HSE163.N-SER147.O 72.41
VAL36.N-LEU89.O 74.05
TRP31.N-CYS16.O 74.23
B-chain – rep2
(continued)
THR257.OG1-LEU253.O 46.28
LEU242.N-ASN231.OD1 46.28
LEU27.N-VAL20.O 47.55
ARG131.NH1-ASP289.OD1 47.55
ASN231.N-LEU227.O 47.55
LEU115.N-VAL148.O 47.91
ARG40.NE-ASP187.OD1 48.46
THR169.OG1-PRO168.O 48.46
ARG40.NH2-ASP187.OD2 48.64
SER147.OG-SER144.O 49.18
TYR239.N-ALA234.O 50.27
THR45.OG1-ASP48.OD2 50.64
THR21.N-LEU67.O 50.64
LEU75.N-VAL68.O 51.00
VAL157.N-LYS100.O 52.09
LYS88.N-SER81.O 52.99
SER123.N-ALA116.O 53.72
ASN95.N-ASP33.O 54.26
GLY109.N-MET130.O 54.63
TYR182.OH-CYS160.O 55.17
HSE172.N-ILE136.O 55.72
GLY146.N-HSE163.O 56.44
SER254.OG-ILE259.O 57.35
LEU89.N-VAL36.O 57.89
VAL20.N-LEU27.O 58.08
GLY149.N-TYR161.O 62.61
LEU167.N-VAL171.O 62.98
TYR37.N-LEU30.O 63.34
ARG131.NH2-ASP289.OD2 63.88
SER267.OG-ASP263.O 64.25
VAL114.N-TYR126.O 67.33
VAL36.N-LEU89.O 70.42
HSE163.N-SER147.O 73.32
TRP31.N-CYS16.O 73.50
B-chain – rep3
Table 2.56 MD-HBs (with occupancy rates ≥30%) of the Mpro-a173v-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
2.4 Concluding Remarks 153
B-chain – rep1
LEU268.N-MET264.O 44.28 THR21.N-LEU67.O 43.19
GLY29.N-VAL18.O 43.74 LEU75.N-VAL68.O 43.56
PHE150.N-SER113.O 45.19
VAL173.N-MET165.O 45.01
LEU242.N-ASN231.OD1 43.74
VAL91.N-ASP34.O 41.20
GLY29.N-VAL18.O 42.11 MET130.N-GLN110.O 42.11
ALA116.N-GLY124.O 39.93
ALA234.N-PHE230.O 39.75
ASN274.N-GLU270.O 38.29
ILE136.N-HSE172.O 37.39
ALA234.N-PHE230.O 37.02
ASN180.N-ASP176.OD2 36.48
ASP153.N-CYS156.O 35.39
ASN133.ND2-GLY195.O 35.75
ARG105.NH1-ASP176.OD2 35.57
LEU87.N-CYS38.O 35.21
ASN221.N-SER267.OG 34.48
SER254.N-LEU250.O 34.48
THR243.OG1-HSE246.ND1 34.48
ARG105.NH2-PHE181.O 33.58
CYS128.N-PHE112.O 35.75
ILE200.N-ASP289.OD2 35.75
ALA266.N-LEU262.O 35.93
MET162.N-THR175.O 35.75
TYR209.OH-ILE259.O 34.85
ALA266.N-LEU262.O 35.57
PHE159.N-LYS102.O 35.57
MET130.N-GLN110.O 36.30
TYR209.OH-ILE259.O 36.12
LYS269.N-CYS265.O 34.30
ILE281.N-SER284.O 35.03
PHE150.N-SER113.O 35.75
THR292.OG1-ASP295.OD1 35.93
ILE281.N-SER284.O 34.85
SER158.N-ASN151.O 36.30 ALA70.N-VAL73.O 36.30
ASP153.N-CYS156.O 36.48
LEU272.N-LEU268.O 36.48
LEU205.N-THR201.O 37.02
SER158.N-ASN151.O 37.75
THR292.OG1-ASP295.OD2 35.39
LEU27.N-VAL20.O 36.48
ASN203.ND2-ASP289.O 36.66
LEU75.N-VAL68.O 35.39
ALA234.N-PHE230.O 37.57
ASN274.N-GLU270.O 37.39
GLN19.N-GLN69.O 35.57
THR135.OG1-ASN133.OD1 35.39
LEU242.N-ASN231.OD1 37.57
VAL18.N-GLY29.O 36.48
CYS265.N-VAL261.O 37.75
ASN180.N-ASP176.OD1 37.57
ARG40.NH2-ASP187.OD2 35.93
LEU30.N-TYR37.O 37.75 ASN180.N-ASP176.OD2 37.75
CYS128.N-PHE112.O 35.75
ILE281.N-SER284.O 37.02 PHE150.N-SER113.O 36.84
CYS128.N-PHE112.O 37.93
ASN203.ND2-ASP289.O 37.75
GLN69.N-GLN19.O 37.93
ARG40.NE-ASP187.OD2 38.11
THR201.OG1-GLU240.O 38.48
SER158.N-ASN151.O 36.30
GLN69.N-GLN19.O 37.21
ALA255.N-GLY251.O 37.39
HSE172.N-ILE136.O 38.11
CYS38.N-LEU87.O 36.12
THR243.OG1-HSE246.ND1 39.20
SER158.N-ASN151.O 38.29
TYR118.N-SER121.O 37.93
ILE200.N-ASP289.OD2 37.39
ARG40.NE-ASP187.OD1 37.39
ASN203.ND2-ASP289.O 36.84
LYS5.NZ-GLU290.OE1 38.48
LEU272.N-LEU268.O 37.75
CYS160.N-GLY149.O 39.38
ARG40.NH2-ASP187.OD2 39.20
TYR118.N-SER121.O 37.93
ARG131.N-THR135.O 38.84 GLN19.N-GLN69.O 38.66
GLN69.N-GLN19.O 37.57
THR21.N-LEU67.O 39.38 THR175.OG1-ASP176.O 38.48
VAL91.N-ASP34.O 39.75
LEU27.N-VAL20.O 39.75
ARG40.NH2-ASP187.OD1 39.75
LEU27.N-VAL20.O 40.65
GLN83.N-VAL86.O 38.48
LYS88.N-SER81.O 39.56
THR243.OG1-HSE246.ND1 39.93
LEU30.N-TYR37.O 38.48
LEU30.N-TYR37.O 40.11
MET130.N-GLN110.O 39.93
PHE150.N-SER113.O 39.38
ALA116.N-GLY124.O 38.84
ALA70.N-VAL73.O 40.11
GLN19.N-GLN69.O 39.75
ALA70.N-VAL73.O 40.83
ILE136.N-HSE172.O 40.47
ASN221.N-SER267.OG 40.29
ILE200.N-ASP289.OD2 40.65 THR135.OG1-ASN133.OD1 40.65
LEU27.N-VAL20.O 39.56
ASN274.N-GLU270.O 40.11
ARG131.NH2-ASP289.OD1 41.38
GLN83.N-VAL86.O 41.74
CYS38.N-LEU87.O 41.20
LEU87.N-CYS38.O 40.29
VAL18.N-GLY29.O 42.83 VAL91.N-ASP34.O 42.65
THR169.OG1-PRO168.O 41.20
CYS160.N-GLY149.O 40.65
LEU205.N-THR201.O 41.02
LYS5.NZ-GLU290.OE1 43.01
THR169.OG1-PRO168.O 43.01
PHE8.N-SER113.OG 44.83
ALA234.N-PHE230.O 40.65
VAL18.N-GLY29.O 42.47
SER254.N-LEU250.O 42.47
GLY29.N-VAL18.O 41.92
LEU272.N-LEU268.O 41.74
MET162.N-THR175.O 41.74
LEU205.N-THR201.O 41.20
ARG131.NH1-ASP289.OD1 42.29
LEU205.N-THR201.O 42.83
ALA116.N-GLY124.O 42.83
SER144.OG-LEU141.O 43.19
VAL91.N-ASP34.O 42.47
ASN221.N-SER267.OG 43.19
LEU268.N-MET264.O 43.92
GLN19.N-GLN69.O 42.83
PHE8.N-SER113.OG 43.56
MET130.N-GLN110.O 43.38
PHE8.N-SER113.OG 44.46
SER147.OG-SER144.O 45.55 LEU75.N-VAL68.O 45.01
GLY29.N-VAL18.O 43.56
VAL173.N-MET165.O 44.46
LEU67.N-THR21.O 45.74
THR135.OG1-ASN133.OD1 45.37
ASN274.N-GLU270.O 44.28
SER10.OG-GLU14.OE1 45.74
ARG131.NH1-ASP289.OD1 43.92
ASN231.N-LEU227.O 44.65
A-chain – rep3 LEU67.N-THR21.O 45.37
A-chain – rep2
GLN83.N-VAL86.O 46.46
A-chain – rep1
LYS5.NZ-GLU290.OE1 44.65
Table 2.56 (continued) B-chain – rep2
THR292.OG1-ASP295.OD2 36.12
ALA116.N-GLY124.O 36.12
ASN203.ND2-ASP289.O 36.48
ASN221.N-SER267.OG 36.66
ARG60.NH1-ASP48.OD2 37.02
GLN69.N-GLN19.O 37.02
ARG105.NH1-ASP176.OD2 37.02
THR243.OG1-HSE246.ND1 37.02
CYS128.N-PHE112.O 37.21
LEU27.N-VAL20.O 37.39
LEU242.N-ASN231.OD1 37.39
PHE150.N-SER113.O 37.57
MET130.N-GLN110.O 37.57
LEU87.N-CYS38.O 37.75
LEU272.N-LEU268.O 37.75
LEU67.N-THR21.O 38.11
ALA70.N-VAL73.O 38.29
LYS5.NZ-GLU290.OE1 38.29
ALA234.N-PHE230.O 38.66
ASP153.N-CYS156.O 38.66
VAL18.N-GLY29.O 39.02
THR135.OG1-ASN133.OD1 39.20
ILE136.N-HSE172.O 39.56
ARG131.NH1-ASP289.OD1 39.56
THR201.OG1-GLU240.O 39.93
VAL91.N-ASP34.O 40.11
ASN274.N-GLU270.O 40.11
SER144.OG-LEU141.O 40.29
SER10.OG-GLU14.OE2 41.56
SER158.N-ASN151.O 41.74
LEU75.N-VAL68.O 41.74
LEU30.N-TYR37.O 42.11
THR21.N-LEU67.O 42.47
GLN19.N-GLN69.O 42.47
LEU205.N-THR201.O 42.65
THR45.OG1-ASP48.OD1 43.01
ASN180.N-ASP176.OD1 43.01
LEU268.N-MET264.O 43.38
B-chain – rep3
ARG131.N-THR135.O 35.75
THR243.OG1-HSE246.ND1 36.48
ALA266.N-LEU262.O 36.48
LYS5.NZ-GLU290.OE1 36.48
MET130.N-GLN110.O 36.66
SER158.N-ASN151.O 36.66
ILE200.N-ASP289.OD2 36.84
ASN180.N-ASP176.OD2 37.02
LEU67.N-THR21.O 37.57
ASN221.N-SER267.OG 37.57
ALA70.N-VAL73.O 38.11
ASP153.N-CYS156.O 38.11
MET162.N-THR175.O 38.11
ALA116.N-GLY124.O 39.02
LEU205.N-THR201.O 39.20
THR135.OG1-ASN133.OD1 39.20
THR45.N-ASP48.OD2 39.38
ALA234.N-PHE230.O 39.38
SER254.N-LEU250.O 39.56
VAL18.N-GLY29.O 40.29
CYS128.N-PHE112.O 40.29
LEU272.N-LEU268.O 40.47
LEU87.N-CYS38.O 40.65
VAL91.N-ASP34.O 41.02
SER144.OG-LEU141.O 41.56
LEU268.N-MET264.O 41.92
THR292.OG1-ASP295.OD2 42.83
PHE150.N-SER113.O 42.83
LEU30.N-TYR37.O 43.01
PHE8.N-SER113.OG 43.19
GLY120.N-ASN28.OD1 43.38
GLN19.N-GLN69.O 43.38
ASN274.N-GLU270.O 43.56
ILE78.N-LYS90.O 44.65
GLN83.N-VAL86.O 45.01
GLY29.N-VAL18.O 45.01
THR201.OG1-GLU240.O 45.37
LYS90.N-GLY79.O 45.74
154 2 3C-Like Protease (3CLpro)
SER254.N-LEU250.O 35.57
THR45.N-ASP48.OD1 32.49
ALA266.N-LEU262.O 30.49
ILE200.N-ASP289.OD1 30.13
ILE106.N-TYR182.OH 30.49
TYR237.OH-GLN273.OE1 30.13
PHE159.N-LYS102.O 31.40
ASN180.N-ASP176.OD1 31.40 TYR118.N-SER121.O 30.49
TYR209.OH-ILE259.O 32.49
SER113.N-PHE150.O 30.67 ALA255.N-GLY251.O 30.67
ARG188.NH1-GLU55.OE2 30.67 ARG188.NH1-GLU55.OE1 30.13
LYS5.NZ-GLU290.OE2 30.49
PHE112.N-CYS128.O 30.49
SER267.N-ASP263.O 31.58
LYS5.NZ-GLU288.OE2 31.58
PHE159.N-LYS102.O 33.39
ARG60.NH2-ASP48.OD2 35.39
PHE159.N-LYS102.O 30.49
LYS5.NZ-GLU288.OE1 30.85 SER113.N-PHE150.O 30.67
ARG60.NH1-ASP56.OD1 30.67 PHE112.N-CYS128.O 30.67
LYS90.NZ-ASP34.OD2 31.03 SER267.N-ASP263.O 31.03
TYR209.OH-ILE259.O 31.03 ARG60.NH1-ASP56.OD2 31.03
GLN256.N-PRO252.O 31.58 TYR118.N-SER121.O 31.22
CYS160.N-GLY149.O 31.22
GLN256.N-PRO252.O 31.40
LYS5.NZ-GLU288.OE1 31.76
ILE281.N-SER284.O 31.76
LYS269.N-CYS265.O 32.49
CYS265.N-VAL261.O 32.67
ALA255.N-GLY251.O 33.21
ILE136.N-HSE172.O 33.39
SER139.N-TYR126.OH 33.76
GLN69.N-GLN19.O 33.76
ASN203.ND2-ASP289.O 33.76
TYR118.N-SER121.O 34.30
ARG131.N-THR135.O 32.12
PHE112.N-CYS128.O 32.49
ALA266.N-LEU262.O 32.67
LYS61.NZ-ASP48.OD1 33.21
CYS265.N-VAL261.O 31.58 CYS160.N-GLY149.O 31.22 ASN221.N-SER267.OG 30.67
SER254.N-LEU250.O 32.85 LYS269.N-CYS265.O 31.03 TYR54.OH-ASP187.O 31.03
VAL104.N-PHE159.O 31.22
TYR209.OH-ILE259.O 31.03
ASN180.N-ASP176.OD2 31.03
LYS269.N-CYS265.O 32.12
CYS160.N-GLY149.O 31.94
ILE200.N-ASP289.OD2 34.12
ASN133.ND2-GLY195.O 34.48
ALA255.N-GLY251.O 34.66
CYS160.N-GLY149.O 35.39
GLY120.N-ASN28.OD1 35.57
ARG131.N-THR135.O 31.76
SER254.N-LEU250.O 32.85 THR243.OG1-HSE246.ND1 32.12
TYR209.OH-ILE259.O 33.03 CYS265.N-VAL261.O 32.85
GLN69.N-GLN19.O 32.49
SER139.N-TYR126.OH 31.94
THR175.OG1-ASP176.O 32.49
ALA70.N-VAL73.O 32.30
ASN203.ND2-ASP289.O 33.21 THR175.OG1-ASP176.O 33.21
ARG105.NH1-ASP176.OD1 33.76 LEU30.N-TYR37.O 33.03
TYR182.N-GLY174.O 33.21
LYS269.N-CYS265.O 32.85
ALA255.N-GLY251.O 32.67
VAL173.N-MET165.O 32.67
CYS38.N-LEU87.O 33.94 PHE159.N-LYS102.O 33.58
SER144.OG-LEU141.O 34.85 CYS128.N-PHE112.O 34.85
PHE159.N-LYS102.O 33.94
ALA255.N-GLY251.O 33.39
ASN180.N-ASP176.OD2 33.03
ALA266.N-LEU262.O 32.85
2.4 Concluding Remarks 155
156
2 3C-Like Protease (3CLpro)
Fig. 2.26 The secondary structures of the optimized Mpro-wt, Mpro-delP168-and-a173v, MprodelP168, and Mpro-a173v dimer models
2.4 Concluding Remarks
157
Fig. 2.27 MD secondary structures of the Mpro-wt-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
Fig. 2.28 MD secondary structures of the Mpro-delP168-and-a173v-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
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2 3C-Like Protease (3CLpro)
Fig. 2.29 MD secondary structures of the Mpro-delP168-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
Fig. 2.30 MD secondary structures of the Mpro-a173v-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
Fig. 2.31 MD-RMSFs of the Mpro-wt-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
2.4 Concluding Remarks
159
Fig. 2.32 MD-RMSFs of the Mpro-delP168-a173v-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
Fig. 2.33 MD-RMSFs of the Mpro-delP168-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
Fig. 2.34 MD-RMSFs of the Mpro-a173v-7bb2 model from the 550 ns MD trajectories (amarolab.ucsd.edu/covid19.php)
Chapter 3
RNA-Dependent RNA Polymerase (RdRp)
Abstract This chapter firstly did the work skillfully and locally by optimizing the structures of RNA-dependent RNA polymerase (RdRp) in complex with its cofactors, i.e., NSP7 and NSP8 (6M71.pdb and 7BTF.pdb), respectively, from COVID-19 virus; then some new structural bioinformatics from the structures optimized for developing therapies of the currently fatal COVID-19 virus are reported. Currently, lots of researchers are using optimization to screen, dock, and design new therapies for COVID-19 but it is not used professionally. The hybrid strategy of mathematical optimization’s neighboring different (local search) algorithms is used professionally in this chapter. For RdRp, we found two new salt bridges: A:GLU729-A:HIS725 and A:GLU610-A:HIS752. The polar contacts A:ASP274-B:ARG111 and A:ARG331-B:ASP112 and the hydrogen bond A:VAL330.NB:VAL115.O (with 51.98% occupancy rate during 10 .μs of molecular dynamics simulation), etc. strongly make the in complex between RdRp and its cofactor Nsp8. Keywords COVID-19 virus · RNA-dependent RNA polymerase (RdRp) · Optimizing cryo-EM structures · Molecular dynamics studies · New structural bioinformatics
3.1 Introduction The COVID-19 virus’ RNA-dependent RNA polymerase (RdRp, also named NSP12) is the central component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug remdesivir [118]. The cryoEM structures for RdRp cofactors (with PDB IDs 6M71 and 7BTF) were recently released into the PDB (www.rcsb.org). This brief chapter will study these structures (optimized) and seek additional useful structural bioinformatics for COVID-19. We also notice that recently the mechanism of RNA capping of SARS-CoV-2 has been presented in [265, 390]; the RNA genome of SARS-CoV-2 contains the 5’ cap that facilitates the translation of viral proteins, protection from exonucleases, and
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_3
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evasion of the host immune response, and decoration of the cap on viral RNA plays essential roles in SARS-CoV-2 proliferation.
3.2 Materials and Methods The materials used in this chapter are 6M71.pdb and 7BTF.pdb. The methods of this chapter are optimizing the structures and confirming from MD trajectory data analyses. The hybrid strategy of mathematical optimization’s neighboring different algorithms is completely the same as the one used in [405, 413]. We optimized the structures locally and slightly, looking at the optimization problem as a three-body problem. The decreased energies (KJ/mol) are .−62125.531 (E102), .−64080.008 (E149), and .−64111.469 (E152) for 6M71.pdb and .−72227.188 (E102), .−75893.664 (E204), and .−76871.992 (E256) for 7BTF.pdb, respectively. The RMSD ([412], Chapter 1) values of the optimized structures from the original structures are 4.783784 Å for 6M71.pdb and 3.040042 Å for 7BTF.pdb, respectively; thus the optimized RdRp cofactor structures are very much different from their original structures. The differences of the 3D structure and secondary structure between each optimized and original structure can be detected by the package MOLMOL [184] and its CalcSecondary output files produced. We also find the openly accessible trajectory data of MD simulations of SARSCoV-2-RdRp with or without template RNA and remdesivir triphosphate from [384], where “the MD simulations were performed using Desmond; the complex models were placed in the orthorhombic box with a buffer distance of 10 Å in order to create a hydration model; TIP3P water model was used for creation of the hydration model; and the MD simulations were performed under the NPT ensemble for 1 .μs on three complex structures using OPLS3e force field.” Six .β-hairpin peptides ◦ ◦ .◦ .◦ .◦ .◦ . .
YKRAKTKYTKRVAGFAKKRK (peptide A), MKRAKTIYTKRVAGFAKKRR (peptide B), MYRAKTIYTKRVAGFAKKLK (peptide C), CKRAKTKYTKRVAGFAKKRC-CONH2 (peptide A-dis), CKRAKTIYTKRVAGFAKKRC-CONH2 (peptide B-dis), and CYRAKTIYTKRVAGFAKKLC-CONH2 (peptide C-dis)
highly affiliated to the N-terminal binding site of the SARS-CoV-2-RdRp NiRAN domain are designed in [321], where for each model of the peptide-RdRp complex (generated from 6M71.pdb and from the peptide VYRAFDIYNDKVAGFAKFLK [136, 204, 263, 321]), the MD trajectories of 20 .μs were released on June 22, 2022, in [321] with DESRES-ANTON codes 15235449, 15235455, 15235444, 15256598, 15256602, and 15256595 in turns for the peptideA-RdRp, peptideBRdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdisRdRp models. We will optimize the six models of the peptide-RdRp complex and then confirm our findings from the 20 .μs MD trajectories of each model (Tables 3.1, 3.2 and 3.3).
3.3 New Results and Discussions
163
3.3 New Results and Discussions For the optimized RdRp cofactors, its Ramachandran plots for 6M71optimized and 7BTFoptimized models are shown in Fig. 3.1 (there is a slight difference between these two plots) implying to us our 6M71optimized and 7BTFoptimized models should be reasonable. The Ramachandran plots are with large percentage of residues in most favored regions so that RdRp factor protein structures could be suitable for docking studies with the compounds.
Fig. 3.1 The Ramachandran plots for the 6M71optimized model and the 7BTFoptimized model
The 3D structures of the 6M71optimized and 7BTFoptimized models have ABCD-Chains: A-Chain is RdRp (i.e., Nsp12) with a .β-hairpin Y21-F48 (Fig. S5 [118] – this is a potential binding site for remdesivir [118]) – C-Chain is Nsp7, and D- and B-Chains are Nsp8 [118]. In this structure of RdRp, there are two disulfide bonds between A:C301 and A:C306 and between A:C487 and A:C645, respectively (Fig. S3 of [118]), binding two Zn.2+ . More theoretical binding sites for the 6M71optimized model may be seen from [235]. The 6M71optimized model has 287 HBs and the 7BTFoptimized model has 385 HBs. The 6M71optimized model has the following 24 SBs: A:GLU665-A:LYS676, A:GLU83-A:LYS73, A:GLU744-A:ARG726, A:ASP452-A:ARG624, A:ASP194A:LYS288, A:GLU729-A:HIS725, A:GLU474-A:ARG305, A:ASP170-A:ARG 173, A:GLU610-A:HIS752, A:GLU474-A:ARG640, A:ASP421-A:LYS417, A:ASP499-A:ARG513, A:ASP258-A:LYS263, A:ASP304-A:ARG640, A:ASP 465-A:ARG132, A:ASP477-A:ARG640, A:ASP274-A:LYS272, A:GLU180A:ARG183, A:GLU136-A:LYS783, A:ASP804-A:LYS807, C:ASP38-C:LYS51, D:ASP112-D:ARG111, A:ASP274-B:ARG111, and D/B:ASP112-A:ARG331, where A:GLU83-A:LYS73 was confirmed by the MD of [321]: “LYS73 in .β3 forms a salt bridge with GLU83 in .αC for most of the simulation” (with HBs A:LYS73.NZ-A:GLU83.OE2 (10.54%) and A:LYS73.NZ-A:GLU83.OE1 (10.54%)). The 7BTFoptimized model has 17 SBs: A:ASP804-A:LYS807, A:ASP291-A:ARG735, A:ASP499-A:ARG513, A:GLU744-A:ARG726, A:ASP 865-A:LYS593, A:GLU474-A:ARG640, C:ASP38-C:LYS51, A:GLU254A:ARG285, A:ASP477-A:ARG640, A:ASP269-B:ARG111, A:GLU474-A:ARG
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3 RNA-Dependent RNA Polymerase (RdRp)
305, A:GLU136-A:LYS783, A:ASP465-A:ARG132, A:ASP421-A:LYS417, A:GLU180-A:ARG183, A:ASP170-A:ARG173, and A:ASP304-A:ARG640. For the 6M71optimized model, we found four .π -cations: B:ARG.+ 111.NH2A:TYR273, A:ARG.+ 624.NH2-A:TYR456, A:ARG.+ 735.NH2-A:TRP290, and A:LYS.+ 272.NZA:PHE275; in A-Chain (i.e., RaRp, Nsp12) 31 .π -.π stackings were found:
PHE415-TYR420, PHE422-TYR887-PHE419-PHE859, PHE881-TYR867, TRP916-PHE594-TYR915, HIS872-TYR831, HIS810-TRP800, TRP617-PHE782, TYR732-TYR728 (with HB TYR732.N-TYR728.O (33.17%)), TYR456-TYR453, PHE571-HIS642, TYR479-TYR746, TYR748-HIS752-TYR770 (with HB HID752.ND1-TYR748.O (11.8%)), TYR787-PHE134, TYR346-PHE348, HIS133TYR129 (with HBs HID133.N-TYR129.O (4.43%) and HID133.ND1-TYR129.O (1.56%)), (2) TYR163-TRP162-PHE157 (2), TYR787-PHE134, (2) TRP268THE275-PHE321, TRP290-PHE313-PHE283, and PHE287-TYR238-TYR237. From [321] with MD trajectory data ID DESRES-ANTON-10917618, we find that the model has 1182 residues and the 10002 ns MD trajectory of data has 8335 frames (with a frame interval of 1.2 ns). We pick up 835 frames with a frame interval of 12 ns to analyze the performances of the 10 .μs MD trajectory. We know that during 2.4–10 .μs, the protein equilibrates around the RMSD value of 5.7 Å. We observe the secondary structure of the whole .10 μs of the MD (Fig. 3.2) and get to know that the following segments have structural changes: A-Chain 446–455, 562–571, 622–625, 733–740, 870–879, 843–855, and 889–917, B-Chain 78–101, C-Chain 17–20 and 62–71, and D-Chain 84–88, 96–113, and 169–179. From the RMSF ([412], Chap. 1) values during the whole 10 .μs (Fig. 3.3), we know that segments 51–71 (the N-terminal part of NiRAN), 258–268, 508–518, and 898–908 (the C-terminal) vary very much during the whole MD of 10 .μs.
Fig. 3.2 The secondary structural developments during the whole 10 .μs of MD
3.3 New Results and Discussions
165
The MD data of [321] can confirm all our SBs of the 6M71optimized model, except that the HIS residues of A:GLU729-A:HIS725 and A:GLU610-A:HIS752 were replaced by ARG726/733/LYS41 and LYS751, respectively. We have shown
Fig. 3.3 The root mean square fluctuation (RMSF) of each residue (numbered from down to up) during the whole 10 .μs of MD
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3 RNA-Dependent RNA Polymerase (RdRp)
in Fig. 3.7 our SBs (A:ASP274-B:ARG111, B:ASP112-A:ARG331, B:ASP112B:ARG111, D:ASP112-D:ARG111, C:ASP38-C:LYS51, A:GLU665-A:LYS676, A:GLU83-A:LYS73, A:GLU744-A:ARG726, A:ASP452-A:ARG624, A:ASP170A:ARG173, A:GLU174-A:ARG640, A:ASP499-A:ARG513, A:ASP304-A:ARG 640, A:ASP465-A:ARG132, A:ASP477-A:ARG640, A:GLU136-A:LYS783) confirmed by the MD data and our HBs confirmed in Table 3.4. We found 5221 HBs; during the whole 10 .μs of MD, most of the HBs in Table 3.4 are not broken except for A:TYR294.OH-ASN314.OD1 (61.92%), broken during 0–47 frames; A:SER343.OG-A:ASP377.OD1 (50.78%), broken during 118–243 and 733–834 frames; and A:SER239.OG-A:ASP465.OD1 (50.54%), broken during 0–38 and 166–203 frames; from Table 3.4 we also found one important HB, A:VAL330.NB:VAL115.O (51.98%), between AB-Chains. These four HBs are shown in Fig. 3.8. The strong polar contacts A:GLU665-A:LYS676, A:GLU744-A:ARG726, A:ASP452-A:ARG624, A:ASP170-A:ARG173, and A:GLU:474-A:ARG640 are with high HB occupancy rates (Table 3.5), and there are two polar contacts, A:ARG331-B:ASP112 and A:ASP274-B:ARG111, between RdRp and Nsp8 (Table 3.5). In addition to these basic and preliminary results, we will further reveal more structural bioinformatics for the PDB entries 6M71, 7BTF, and 7BV1 and 7BV2 [394]. We analyze the MD data of [384] – MD trajectory data of SARS-CoV-2-RdRp with or without template RNA and remdesivir triphosphate. Tables 3.6, 3.8 and 3.9 respectively list the HBs (with more than 55% occupancy rates from the analyses of the 1 .μs MD trajectory data) and all the existing SBs (from the analyses of the 1 .μs MD trajectory data) of SARS-CoV-2 RdRp with template RNA and remdesivir triphosphate, and Tables 3.7, 3.10 and 3.11 respectively list the HBs (with more than 55% occupancy rates from the analyses of the 1 .μs MD trajectory data) and all the existing SBs (from the analyses of the 1 .μs MD trajectory data) of SARSCoV-2 RdRp without template RNA and remdesivir triphosphate. From MD data of [384], we can confirm all the SBs of the 6M71optimized and 7BTFoptimized models except for SBs A:GLU83-A:LYS73 and A:GLU610-A:HIS752, and the SB A:GLU610-A:HIS752 was replaced by A:GLU610-A:LYS751 (Tables 3.8, 3.9, 3.10 and 3.11). For Mpro, Yamamoto et al. (2020) reported that “although nitro groups were enriched in the substructure of the hit compounds, they did not significantly contribute to the binding interaction in the predicted docking poses” [385]. Next, we specially discuss the SARS-CoV-2-RdRp domain (mainly in the NiRAN domain) binding with some .β-hairpin peptides. We optimized the six models of peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp [321] and got the following RdRp residues binding with each peptide (Fig. 3.4): ◦ peptide A: LYS11, TYR12, THR13, ALA15, ASP16, VAL18, TYR19, ALA20, ARG22, HIS23, ASN28, THR31, LEU32, GLU34, ILE35, VAL94, THR96, LEU97, ASP98, ASN99, TYR107, ASP108, ASP111, SER126, LEU130, ASN595, LEU598, SER599, THR600, ASP601, GLY602, ASN603, LYS604,
.
3.3 New Results and Discussions
167
ARG611, GLN614, HIS615, LEU617, TYR618, GLU619, ARG623; ◦ peptide B: ILE4, ARG6, LYS11, TYR12, THR13, ALA15, ASP16, VAL18, TYR19, ARG22, HIS23, CYS29, ASP30, THR31, LEU32, ILE35, VAL94, THR96, LEU97, ASP98, ASN99, TYR107, ASP108, GLY110, VAL123, SER126, LEU130, ASN595, LEU598, SER599, THR600, ASP601, GLY602, ASN603, LYS604, ARG611, ASN612, GLN614, HIS615, TYR618, GLU619, TYR622, ARG623; .◦ peptide C: THR10, LYS11, TYR12, THR13, ALA15, ASP16, VAL18, TYR19, ARG22, HIS23, ASN28, CYS29, THR31, LEU32, VAL94, THR96, LEU97, ASP98, SER126, LEU130, LEU598, SER599, THR600, ASP601, GLY602, ASN603, LYS604, ILE605, ARG611, GLN614, HIS615, TYR618, GLU619, TYR622, ARG623; .◦ peptide A-dis: LYS11, TYR12, THR13, ALA15, ASP16, VAL18, TYR19, HIS23, GLY27, ASN28, THR31, VAL94, THR96, LEU97, ASP98, ASN99, TYR107, ASP111, SER126, TYR127, LEU130, GLN358, LEU598, SER599, THR600, ASP601, GLY602, ASN603, LYS604, ILE605, ARG611, GLN614, HIS615, TYR618, GLU619, ARG623; .◦ peptide B-dis: THR10, LYS11, TYR12, THR13, ALA15, ASP16, VAL18, TYR19, ALA20, ARG22, HIS23, ASP25, GLY27, ASN28, ASP30, THR31, VAL94, THR96, LEU97, ASP98, ASN99, TYR107, ASP108, ASP111, SER126, LEU130, ASN595, LEU598, SER599, THR600, ASP601, GLY602, ASN603, LYS604, ILE605, LYS608, ARG611, ASN612, GLN614, HIS615, TYR618, GLU619, TYR622, ARG623; .◦ peptide C-dis: LEU9, LYS11, TYR12, THR13, ALA15, ASP16, VAL18, TYR19, ALA20, ARG22, HIS23, PHE24, ASN28, CYS29, THR31, LEU32, THR96, LEU97, VAL94, ASP98, ASN99, TYR107, SER126, LEU130, GLN358, ASN595, LEU598, SER599, THR600, ASP601, GLY602, ASN603, LYS604, ILE605, ARG611, ASN612, GLN614, HIS615, TYR618, GLU619, TYR622, ARG623; .
where the RdRp residues are labeled as aa PRO2-LEU786 (with ACE and NME at the N- and C-terminals, respectively; the residue labels plus 110 will agree with the ones in A-chain of PDB 6M71 where A:CYS301.SG-A:CYS306.SG and A:CYS487.SG-A:CYS645.SG) and the peptide is labeled as aa 31–50. Thus, the RdRp residues are aa ILE114-LEU240 in NiRAN domain (aa 51–249), GLN468 in Finger, and aa ASN705-ARG633 in the palm subdomain (aa 680–815). Each peptide should insert into the groove clamped by the NiRAN domain (aa 51–249) and the palm subdomain (aa 680–815) in the SARS-Cov-2-RdRp [118] and link to the RdRp Finger by residue GLN468. All the six models have the same SB P:LYS48-A:ASP711 (Tables 3.1 and 3.2 and Fig. 3.6) as confirmed below (but for model peptideC-RdRp, it is broken during 13.9–20 .μs). For the optimized peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models, we find the HBs, SBs, and .π -interactions between the peptide and the RaRp from Table 3.1 and Fig. 3.4, where P-chain is the peptide aa 31–50 and A-chain is the RdRp aa PRO2-LEU786 (where these residue labels plus 110 will agree with the ones
168
3 RNA-Dependent RNA Polymerase (RdRp)
in the A-chain of PDB 6M71). Table 3.12 lists the SBs within the RaRp of the optimized peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models in [321]. All the six peptides in the optimized models have positive Poisson-Boltzmann electrostatic potential surfaces (EPS), and within RaRp around residues GLU364 and ASP389, and bottom residues CYS42.→AS342.→ASP54.→THR31.→TYR509 .→PHE672.→SER599.→ALA652-ALA667.→THR600 have positive EPS. The MD secondary structural performance of the peptideA-RdRp, peptideBRdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdisRdRp models in [321] can be seen from Fig. 3.5. We may see that some .α-helices unfold: ◦ model peptideA-RdRp: segment aa VAL147-LYS162; ◦ model peptideB-RdRp: segment aa ASN387-ALA402; .◦ model peptideC-RdRp: segments aa HID252-ASP267, around ASP342 (8– 20 .μs), aa ASN387-ALA402 (3.8–10.2 .μs); .◦ model peptideAdis-RdRp: around LEU327; .◦ model peptideBdis-RdRp: around ASP342 (17.4–20 .μs), ALA402 (8.9– 11.4 .μs); . .
Fig. 3.4 The six peptides (YKRAKTKYTKRVAGFAKKRK, MKRAKTIYTKRVAGFAKKRR, MYRAKTIYTKRVAGFAKKLK, CKRAKTKYTKRVAGFAKKRC-CONH2, CKRAKTIYTKRVAGFAKKRC-CONH2, CYRAKTIYTKRVAGFAKKLC-CONH2) interacting with SARS-CoV-2-RdRp in their optimized models of [321]: up from left to right – peptideARdRp, peptideB-RdRp, and peptideC-RdRp ; down from left to right – peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp
3.3 New Results and Discussions
169
◦ model peptideCdis-RdRp: around ASP342 (11.4–20 .μs), ALA402 (8–20 .μs).
.
The SBs of RdRp in the optimized models and during 20 .μs MDs can be seen from Tables 3.12 and 3.13. The MD-HBs between the peptide and RdRp (with occupancy rates .≥5%) and within the peptide (with occupancy rates .≥5%) can be seen from Table 3.3. Within RdRp, during 20 .μs MDs, the SBs and HBs (with occupancy rates .≥35%) can be seen from Tables 3.13, 3.14 and Tables 3.15, 3.16, respectively. Do remember in these tables the residue labels plus 110 will agree with the ones in the A-chain of PDB 6M71. From Tables 3.13 and 3.14, we can confirm the following SBs: A:GLU744A:ARG726 (GLU634-ARG616), A:ASP452-A:ARG624 (ASP342-ARG514), A:ASP170-A:ARG173 (ASP60-ARG63), A:GLU474-A:ARG640 (GLU364ARG530), A:ASP499-A:ARG513 (ASP389-ARG403), A:ASP304-A:ARG640 (ASP194-ARG530), A:ASP465-A:ARG132 (ASP355-ARG22), A:ASP477A:ARG640 (ASP367-ARG530), A:GLU136-A:LYS783 (GLU26-LYS673) of RdRp during the 20 .μs MD simulations for the peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models (Fig. 3.6).
Fig. 3.5 The MD secondary structures of the six models of [321]; each model has 20 .μs MD trajectories – here we pick up 200 frames with “frameStride .= 0.1 .μs”: up from left to right – peptideA-RdRp, peptideB-RdRp, and peptideC-RdRp ; down from left to right – peptideAdisRdRp, peptideBdis-RdRp, and peptideCdis-RdRp
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3 RNA-Dependent RNA Polymerase (RdRp)
Fig. 3.6 The six models, peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp, all have the same MD-SB P:LYS48-A:ASP711 (but for model peptideC-RdRp, it is broken during 13.9–20 .μs)
3.4 Concluding Remarks In molecular structural studies, optimization is a very useful tool; for example, in [406] the author used optimization hybrid strategies of simulated annealing and local search methods and found that the prion AGAAAA amyloid fibril structure is the Class 7 structure of amyloid fibrils – recently the Class 7 was confirmed by Glynn et al. [124]. Thus, the hybrid strategy of mathematical optimization’s neighboring different (local search) algorithms could be very effective in this chapter. Moreover, this chapter will also present some preliminary structural bioinformatics for developing therapies of the currently fatal COVID-19 virus (Figs 3.7 and 3.8).
Supplementary Information
171
Supplementary Information
Fig. 3.7 Some interesting SBs of the 6M71optimized model confirmed by the 10 μs MD trajectory data of [321]
172
Fig. 3.7 (continued)
3 RNA-Dependent RNA Polymerase (RdRp)
A:ASP98.OD1-P:LYS35.NZ*P:THR36.N-A:ASP98.OD2
P:TYR38.OH-A:GLU619.OE1 P:ARG41.NH1-A:ASN603.OD1
P:ARG33.NE-A:ASP16.OD2 *
P:ALA34.N-A:ASP16.OD2
P:LYS48.NZ-A:ASP601.OD1*-
P:LYS48.NZ-A:ASP601.OD1 *
P:ARG33.NH1-A:ASP16.OD2 *
P:ARG33.NH2-A:LYS11.O
P:ALA34.N-A:ASP16.OD1
P:LYS35.NZ-A:ASP98.OD1 *
P:LYS48-A:ASP601
P:ILE37.N-P:GLY44.O P:LYS48.N-P:ARG33.O
P:LYS35-A:ASP98
P:LYS48-A:ASP601
A:TYR19-P:LYS47.NZ+
P:LYS32.NZ-P:LYS47.O
P:ARG33.N-P:LYS48.O
P:ILE37.N-P:GLY44.O
P:LYS48.N-P:ARG33.O
P:LYS48-A:ASP601
P:TYR38-A:ARG623.NE+
P:TYR31.N-P:LYS50.OXT
P:LYS50.NZ-P:LYS50.O
P:LYS50.OXT-P:TYR31.N P:LYS50.O-P:LYS35.NZ
P:LYS35.NZ-P:LYS50.O
P:ARG33.N-P:LYS48.O
A:TYR12-P:ARG33.NH2+
P:ARG33-A:ASP16
P:ARG33-A:ASP16
P:LYS35-A:ASP98
P:LYS47.NZ-P:LYS32.O
P:ARG33.N-P:LYS48.O
P:CYS31.N-P:CYS50.O
P:ARG49.NH2-P:ARG49.O
P:LYS48.N-P:ARG33.O
P:LYS48-A:ASP601
P:LYS48-A:ASP601 A:TYR19-P:LYS47.NZ+
P:LYS35-A:ASP98
P:ARG33-A:ASP16
P:LYS32-A:ASP30
A:ASP601.OD1-P:LYS48.NZ*-
P:LYS48.NZ-A:ASP601.OD1 *
P:LYS47.NZ-A:THR31.OG1
P:LYS47-A:ASP16
P:LYS37-A:ASP98
P:LYS35-A:ASP98
P:ALA43.N-A:GLN614.OE1 P:PHE45.N-A:LEU598.O
P:LYS48.NZ-A:ASP601.OD1 * A:ASP601.OD1-P:LYS48.NZ*-
A:ASP601.OD1-P:LYS48.NZ*-
P:LYS48.NZ-A:ASP601.OD1 *
P:ALA43.N-A:GLN614.OE1
P:THR36.N-A:ASP98.OD1 P:THR36.OG1-A:ASP98.OD1
P:LYS47.NZ-A:ASP16.OD1 * P:LYS47.NZ-A:THR31.OG1
P:THR36.OG1-A:ASP98.OD2
P:TYR38.OH-A:GLU619.OE2
P:LYS35.NZ-A:ASP98.OD2 * A:ASP98.OD2-P:LYS35.NZ*-
P:LYS37.NZ-A:ASP98.OD1 * P:TYR38.OH-A:GLU619.OE1
P:ALA34.N-A:ASP16.OD1
A:ASP16.OD2-P:ARG33.NH1*-
P:ARG33.NH1-A:ASP16.OD2 *
A:ASP30.OD2-P:LYS32.NZ*-
A:ASP98.OD1-P:LYS35.NZ*-
P:LYS37.NZ-A:ASN99.OD1
P:LYS35.NZ-A:ASP98.OD1 *
Model peptideBdis-RdRp P:LYS32.NZ-A:ASP30.OD2 *
P:THR36.N-A:ASP98.OD2
P:LYS48.NZ-A:ASP601.OD1 *
P:THR36.N-A:ASP98.OD1
Model peptideAdis-RdRp P:ARG33.NH2-A:LYS11.O
Model peptideC-RdRp P:ARG33.NH2-A:LYS11.O
Model peptideB-RdRp
P:ARG33.NH2-A:ASP16.OD1 *
Model peptideA-RdRp
P:TYR31.OXTYR12.OH
P:LYS48.N-P:ARG33.O
P:LYS35.N-P:ALA46.O
P:ARG33.N-P:LEU49.O
P:TYR38-A:AR623.NH2+
A:TYR12-P:ARG33.NH2+
P:LYS48-A:ASP601
P:LYS35-A:ASP98
P:ARG33-A:ASP16
A:ASP601.OD1-P:LYS48.NZ*-
P:LYS48.NZ-A:ASP601.OD1 *
P:THR36.OG1-A:ASP98.OD2
P:THR36.N-A:ASP98.OD2
A:ASP98.OD1-P:LYS35.NZ*-
P:LYS35.NZ-A:ASP98.OD1 *
P:ALA34.N-A:ASP16.OD1
P:ARG33.NH2-A:LYS11.O
P:ARG33.NH1-A:ASP16.OD2 *
Model peptideCdis-RdRp
Table 3.1 The HBs, SBs, and π-cations between the peptide (P-chain) and the RaRp (A-chain) of the peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models in [321] are optimized, where * means that at the same time, there exists an SB between the residues. The HBs within each peptide are also shown
Supplementary Information 173
174
3 RNA-Dependent RNA Polymerase (RdRp)
Table 3.2 The 20 μs MD-SBs between the peptide (P-chain) and the RaRp (A-chain) of the peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models in [321] Model peptideA-RdRp
Model peptideB-RdRp
Model peptideC-RdRp
Model peptideAdis-RdRp
Model peptideBdis-RdRp
Model peptideCdis-RdRp
A:ASP111-P:LYS37
A:ASP16-P:ARG33
A:ASP16-P:ARG33
A:ASP111-P:LYS37
A:ASP108-P:ARG33
A:ASP16-P:ARG33
A:ASP16-P:ARG33
A:ASP25-P:LYS47
A:ASP601-P:LYS47
A:ASP16-P:ARG33
A:ASP111-P:LYS35
A:ASP25-P:LYS47
A:ASP25-P:ARG49
A:ASP30-P:ARG49
A:ASP601-P:LYS48
A:ASP16-P:LYS35
A:ASP16-P:ARG33
A:ASP601-P:LYS47
A:ASP25-P:LYS32
A:ASP30-P:LYS32
A:ASP98-P:ARG33
A:ASP30-P:LYS32
A:ASP16-P:LYS35
A:ASP601-P:LYS48
A:ASP25-P:LYS47
A:ASP601-P:ARG49
A:ASP98-P:LYS35
A:ASP601-P:ARG49
A:ASP25-P:LYS32
A:ASP98-P:ARG33
A:ASP30-P:ARG33
A:ASP601-P:LYS48
A:ASP98-P:LYS48
A:ASP601-P:LYS37
A:ASP25-P:LYS47
A:ASP98-P:LYS35
A:ASP30-P:LYS32
A:ASP98-P:ARG50
A:ASP98-P:LYS50
A:ASP601-P:LYS47
A:ASP30-P:LYS32
A:ASP601-P:ARG49
A:ASP98-P:LYS35
A:ASP601-P:LYS48
A:ASP601-P:LYS47
A:ASP601-P:LYS37
A:GLU26-P:ARG49
A:ASP98-P:LYS35
A:ASP601-P:LYS48
A:ASP601-P:LYS48
A:GLU26-P:LYS32
A:ASP98-P:LYS37
A:ASP98-P:LYS35
A:ASP601-P:LYS50
A:GLU26-P:LYS47
A:ASP98-P:LYS48
A:ASP98-P:LYS48
A:ASP98-P:ARG33 A:ASP98-P:LYS35 A:ASP98-P:LYS37 A:ASP98-P:LYS48
Fig. 3.8 Some interesting HBs of the 6M71optimized model confirmed by the 10 μs MD trajectory data of [321]
P:LYS47.NZ-SER599.O 7.46 P:CYX31.N-ASP30.OD1 5.97
P:THR36.N-ASP98.OD2 21.89
P:THR36.N-ASP98.OD1 19.40
P:THR36.OG1-ASP98.OD1 14.93
P:ALA34.N-ASP16.OD2 11.94
P:THR36.OG1-ASP98.OD2 10.95
P:ALA34.N-ASP16.OD1 9.45
P:LYS48.NZ-ASP601.OD2 9.45
P:LYS47.NZ-ASP25.OD2 9.45
GLN614.NE2-P:ALA43.O 7.46
P:LYS48.NZ-ASP601.OD1 6.97
P:LYS47.NZ-THR31.OG1 6.47
P:ARG33.NH2-ASP16.OD1 6.47
P:LYS47.NZ-ASP25.OD1 5.97
P:THR36.N-ASP98.OD1 24.88
P:ALA34.N-ASP16.OD2 19.90
P:THR36.N-ASP98.OD2 17.41
P:ARG33.NE-ASP16.OD2 11.94
GLN614.NE2-P:ALA43.O 11.44
P:ALA34.N-ASP16.OD1 9.95
P:TYR31.OH-ASP16.OD1 9.45
P:ARG33.NH2-ASP16.OD1 7.96
P:ALA43.N-GLN614.OE1 6.97
P:TYR31.N-ASN28.OD1 5.97
P:THR36.OG1-ASP98.OD2 5.47
P:LYS32.N-THR31.OG1 5.47
TYR618.OH-P:THR36.OG1 5.47
P:THR39.N-P:VAL42.O 50.75
P:LYS35.N-P:ALA46.O 42.79
P:VAL42.N-P:THR39.OG1 38.81
P:LYS48.N-P:ARG33.O 28.86
P:ARG33.N-P:LYS48.O 15.92
P:ALA46.N-P:LYS35.O 7.46
P:VAL42.N-P:THR39.OG1 29.35
P:LYS37.N-P:GLY44.O 28.86
P:LYS35.N-P:ALA46.O 28.86
P:LYS48.N-P:ARG33.O 25.37
P:ALA46.N-P:LYS35.O 17.41
P:GLY44.N-P:LYS37.O 10.45
P:MET31.N-P:ARG50.OXT 5.47
P:ARG50.N-P:MET31.O 7.46
P:ILE37.N-P:GLY44.O 53.73
P:THR39.N-P:VAL42.O 53.23
P:LYS35.NZ-ASP98.OD1 5.47
Model peptideAdis-RdRp
P:GLY44.N-P:LYS37.O 8.96
P:LYS50.N-P:MET31.O 5.47
P:LYS47.NZ-P:PHE45.O 7.46
P:ARG33.NH1-P:LYS32.O 7.46
P:ALA46.N-P:LYS35.O 19.40
P:LYS48.N-P:ARG33.O 24.88
P:LYS37.N-P:GLY44.O 27.36
P:VAL42.N-P:THR39.OG1 28.86
P:ARG33.N-P:LYS48.O 33.33
P:LYS35.N-P:ALA46.O 41.79
P:THR39.N-P:VAL42.O 43.28
P:LYS32.N-THR31.OG1 7.96
P:ALA34.N-ASP16.OD2 10.45
P:LYS47.NZ-ASP601.OD1 14.43
P:LYS47.NZ-ASP601.OD2 14.43
P:PHE45.N-LEU598.O 17.91
GLN614.NE2-P:ALA43.O 18.91
P:THR36.N-ASP98.OD2 22.89
P:THR36.N-ASP98.OD1 27.36
P:ARG33.N-P:LYS48.O 10.95
P:ALA46.N-P:LYS35.O 15.42
P:VAL42.N-P:THR39.OG1 34.33
P:LYS48.N-P:ARG33.O 39.30
P:LYS35.N-P:ALA46.O 40.80
P:ILE37.N-P:GLY44.O 44.28
P:THR39.N-P:VAL42.O 56.22
P:LYS48.NZ-ASP601.OD1 6.47
P:THR36.OG1-ASP98.OD1 8.46
P:ALA34.N-ASP16.OD2 8.96
P:THR36.OG1-ASP98.OD2 12.44
GLN614.NE2-P:ALA43.O 13.43
P:THR36.N-ASP98.OD2 19.90
P:ALA34.N-ASP16.OD1 20.90
P:THR36.N-ASP98.OD1 29.35
P:ALA34.N-ASP16.OD1 36.82
HIP615.NE2-P:THR39.O 46.77
Model peptideC-RdRp
P:PHE45.N-LEU598.O 41.29
P:PHE45.N-LEU598.O 32.84 P:PHE45.N-LEU598.O 35.82
HIP615.NE2-P:THR39.O 49.25
Model peptideB-RdRp
HIP615.NE2-P:THR39.O 47.26
Model peptideA-RdRp
HIP615.NE2-P:THR39.O 36.32
P:ARG33.NH1-P:LYS32.O 7.46
P:CYX50.N-P:CYX31.O 13.93
P:ALA46.N-P:LYS35.O 13.93
P:ARG33.N-P:LYS48.O 29.85
P:VAL42.N-P:THR39.OG1 31.84
P:ILE37.N-P:GLY44.O 36.32
P:LYS48.N-P:ARG33.O 36.32
P:LYS35.N-P:ALA46.O 49.75
P:THR39.N-P:VAL42.O 53.23
P:THR36.OG1-ASP98.OD2 9.45
P:THR36.OG1-ASP98.OD1 9.45
P:ALA34.N-ASP16.OD1 14.93
GLN614.NE2-P:ALA43.O 15.42
P:THR36.N-ASP98.OD1 16.92
P:ALA34.N-ASP16.OD2 17.91
P:THR36.N-ASP98.OD2 23.88
P:PHE45.N-LEU598.O 33.83
HIP615.NE2-P:THR39.O 56.72
Model peptideBdis-RdRp
P:ALA46.N-P:LYS35.O 11.94
P:CYX50.N-P:CYX31.O 13.93
P:ARG33.N-P:LYS48.O 26.87
P:VAL42.N-P:THR39.OG1 35.32
P:ILE37.N-P:GLY44.O 39.80
P:LYS35.N-P:ALA46.O 41.29
P:LYS48.N-P:ARG33.O 47.26
P:THR39.N-P:VAL42.O 55.72
P:THR36.OG1-ASP98.OD2 8.96
P:THR36.OG1-ASP98.OD1 8.96
P:ALA34.N-ASP16.OD1 10.45
P:ALA34.N-ASP16.OD2 11.44
GLN614.NE2-P:ALA43.O 16.42
P:THR36.N-ASP98.OD2 18.91
P:THR36.N-ASP98.OD1 24.38
P:PHE45.N-LEU598.O 38.81
HIP615.NE2-P:THR39.O 50.75
Model peptideCdis-RdRp
Table 3.3 The 20 μs MD-HBs (with occupancy rates ≥5%) between the peptide (P-chain) and the RaRp (A-chain) of the peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models in [321] and the MD-HBs (with occupancy rates ≥5%) within the peptide (P-chain)
Supplementary Information 175
176 Table 3.4 The HBs with more than 50% occupancy rates from the analyses of the 10 μs MD trajectory data of [321]
3 RNA-Dependent RNA Polymerase (RdRp) Donor
Acceptor
Occupancy
B/D:ILE132.N
B/D:LEU184.O
79.04%
B/D:THR141.OG1
B/D:THR137.O
78.20%
B/D:LYS139.N
B/D:TYR135.O
74.85%
B/D:ALA188.N
B/D:LEU128.O
74.49%
B/D:ILE185.N
B/D:VAL160.O
73.77%
B/D:VAL186.N
B/D:VAL130.O
73.17%
B/D:LEU128.N
B/D:ALA188.O
71.74%
B/D:GLN157.N
B/D:THR187.O
71.50%
B/D:GLU155.N
B/D:LEU189.O
69.10%
A:THR319.OG1
A:LEU316.O
68.26%
C:THR9.OG1
C:ASP5.O
68.14%
B/D:THR187.N
B/D:GLN158.O
67.19%
A:THR148.OG1
A:GLU144.O
67.07%
A:THR701.OG1
A:CYS697.O
66.23%
B/D:VAL130.N
B/D:VAL186.O
65.87%
A:VAL764.N
A:MET615.O
64.91%
B/D:ASN176.ND2
B/D:GLU171.O
64.91%
B/D:TRP154.NE1
B/D:TYR149.O
64.19%
A:THR248.OG1
A:ILE244.O
63.23%
B/D:SER177.OG
B/D:SER173.O
63.11%
B/D:THR137.OG1
B/D:ASP134.OD1
62.75%
A:TYR294.OH
A:ASN314.OD1
61.92%
B/D:ILE156.N
B/D:THR145.O
61.56%
B/D:THR137.OG1
B/D:ASP134.OD2
61.32%
A:TYR237.OH
A:GLN210.OE1
61.08%
B/D:ALA191.N
B/D:LEU153.O
61.08%
B/D:THR123.OG1
B/D:ILE119.O
59.64%
A:SER681.OG
A:GLU665.OE2
59.40%
B/D:THR124.OG1
B/D:ILE120.O
59.16%
A:THR604.OG1
A:ASN600.O
59.16%
B/D:CYS142.N
B/D:TYR138.O
58.20%
A:ASP211.N
A:ASN215.O
57.13%
A:THR870.OG1
A:TYR867.O
56.53%
A:VAL535.N
A:ASN356.OD1
56.17%
A:GLN789.NE2
A:GLN698.OE1
55.09%
B/D:PHE147.N
B/D:TRP154.O
54.97%
A:THR582.OG1
A:SER578.O
54.49%
A:TYR787.OH
A:TYR163.O
54.37%
A:THR252.OG1
A:ARG249.O
54.13%
C:SER57.OG
C:VAL53.O
53.53%
B/D:THR93.OG1
B/D:THR89.O
52.69%
B/D:LEU189.N
B/D:GLU155.O
52.22%
A:VAL330.N
B:VAL115.O
51.98%
A:GLN822.N
A:ASP825.O
51.50%
B/D:VAL160.N
B/D:ILE185.O
50.90%
A:TYR884.OH
A:ILE837.O
50.90%
A:SER343.OG
A:ASP377.OD1
50.78%
A:TRP216.N
A:ALA95.O
50.78%
A:SER709.OG
A:ASN705.O
50.66%
A:VAL820.N
A:VAL827.O
50.54%
A:SER239.OG
A:ASP465.OD1
50.54%
A:VAL202.N
A:ILE223.O
50.18%
A:VAL667.N
A:TYR674.O
50.18%
A:ASN416.N
A:CYS842.O
50.18%
A:SER384.OG
A:MET380.O
50.18%
Supplementary Information Table 3.5 The HBs for some important SBs of the 6M71optimized model from the analyses of the 10 μs MD trajectory data of [321]
177 Donor
Acceptor
Occupancy
A:ARG331.NH1
B:ASP112.O
A:ARG331.NH2
B:ASP112.OD2
A:ARG331.NH2
B:ASP112.O
A:ARG331.NH2
B:ASP112.OD1
A:ARG331.NH1
B:ASP112.OD1
A:ARG331.NH1
B:ASP112.OD2
A:ARG331.NE
B:ASP112.O
B:ARG111.NH2
A:ASP274.OD2
B:ARG111.NH2
A:ASP274.OD1
B:ARG111.NH1
A:ASP274.OD1
B:ARG111.NH1
A:ASP274.OD2
B:ARG111.NE
A:ASP274.OD1
B:ARG111.NE
A:ASP274.OD2
D/B:ARG111.NE
D/B:ASP112.OD1
D/B:ARG111.NH2
D/B:ASP112.OD1
D/B:ARG111.NH2
D/B:ASP112.OD2
D/B:ARG111.NE
D/B:ASP112.OD2
D/B:ARG111.NH1
D/B:ASP112.OD1
D/B:ARG111.NH1
D/B:ASP112.OD2
D/B:ARG111.NE
D/B:ASP112.O
C:LYS51.NZ
C:ASP38.OD2
C:LYS51.NZ
C:ASP38.OD1
C:LYS51.NZ
C:ASP38.O
A:LYS676.NZ
A:GLU665.OE1
A:LYS676.N
A:GLU665.O
10.78% 4.55% 4.43% 4.43% 0.60% 0.48% 0.24% 13.29% 11.38% 3.95% 3.59% 3.23% 2.28% 7.90% 7.90% 7.66% 6.83% 1.44% 1.08% 0.24% 19.88% 18.32% 0.48% 40.00% 34.01% 0.96% 10.54% 10.54% 19.28% 18.20% 18.20% 17.60% 37.01% 19.40% 2.04% 0.84% 0.60% 26.23% 25.75% 20.60% 17.60% 3.95% 1.08% 0.60% 31.98% 28.14% 27.78% 22.75% 13.05% 10.06% 9.70% 9.46% 3.11% 22.28% 19.52% 17.25% 17.49% 11.26% 15.21% 13.29% 0.12% 0.12% 17.96% 15.69%
A:LYS676.NZ
A:GLU665.OE2
A:LYS73.NZ
A:GLU83.OE2
A:LYS73.NZ
A:GLU83.OE1
A:ARG726.NH1
A:GLU744.OE2
A:ARG726.NH2
A:GLU744.OE1
A:ARG726.NH2
A:GLU744.OE2
A:ARG726.NH1
A:GLU744.OE1
A:ARG624.NH2
A:ASP452.OD1
A:ARG624.NH2
A:ASP452.OD2
A:ARG624.NE
A:ASP452.OD2
A:ARG624.NE
A:ASP452.OD1
A:ARG624.NE
A:ASP452.O
A:ARG173.NE
A:ASP170.OD2
A:ARG173.NH2
A:ASP170.OD1
A:ARG173.NH2
A:ASP170.OD2
A:ARG173.NE
A:ASP170.OD1
A:ARG173.N
A:ASP170.O
A:ARG173.NH1
A:ASP170.OD1
A:ARG173.NH1
A:ASP170.OD2
A:ARG640.NH2
A:GLU474.OE2
A:ARG640.NH2
A:GLU474.OE1
A:ARG640.NH1
A:GLU474.OE1
A:ARG640.NH1
A:GLU474.OE2
A:ARG513.NH2
A:ASP499.OD1
A:ARG513.NH2
A:ASP499.OD2
A:ARG513.NE
A:ASP499.OD2
A:ARG513.NE
A:ASP499.OD1
A:ARG513.NH1
A:ASP499.OD1
A:ARG640.NH2
A:ASP304.OD2
A:ARG640.NH2
A:ASP304.OD1
A:ARG640.NE
A:ASP304.OD2
A:ARG132.NH1
A:ASP465.OD2
A:ARG132.NH2
A:ASP465.OD2
A:ARG640.NH1
A:ASP477.OD1
A:ARG640.NH1
A:ASP477.OD2
A:ARG640.NH2
A:ASP477.OD1
A:ARG640.NE
A:ASP477.OD2
A:LYS783.NZ
A:GLU136.OE2
A:LYS783.NZ
A:GLU136.OE1
Table 3.6 The HBs with more than 55% occupancy rates from the analyses of the 1 μs MD trajectory data of SARS-CoV-2 RdRp with template RNA and remdesivir triphosphate [384]
Donor-acceptor
Occupancy
ARG392.NE-ASP390.OD1
87.72%
ARG173.NE-ASP170.OD1
87.33%
ARG392.NH2-ASP390.OD2
86.56%
ARG173.NH2-ASP170.OD2
86.28%
ARG132.NH2-ASP465.OD2
83.78%
ARG640.NH2-GLU474.OE2
82.92%
TYR156.OH-ASP170.OD2
78.60%
THR394.N-ASP454.OD1
78.60%
ARG654.NH2-ASN568.OD1
77.74%
ARG640.NH1-GLU474.OE1
75.34%
ARG513.NH2-ASP499.OD1
74.47%
HIP256.ND1-LYS263.O
74.18%
ARG197.NE-TYR289.OH
73.32%
SER343.N-ASP377.OD2
72.84%
THR531.OG1-PHE528.O
72.65%
ARG513.NE-ASP499.OD2
72.36%
TYR653.OH-HIS355.O
69.96%
TYR674.OH-ASP390.OD2
69.87%
ALA512.N-LYS500.O
69.29%
ARG640.NE-ASP304.OD2
68.91%
ARG197.NH2-ASP194.OD1
68.81%
TYR787.OH-TYR163.O
68.52%
THR701.OG1-CYS697.O
67.66%
SER239.OG-ASP465.OD1
67.18%
THR319.OG1-LEU316.O
67.08%
LEU469.N-ASP465.O
66.89%
ARG624.NH2-ASP452.OD1
66.41%
TYR884.OH-ILE837.O
66.31%
CYS765.N-SER754.O
66.12%
ASN37.ND2-ALA443.O
66.03%
SER692.OG-ALA688.O
65.83%
THR394.OG1-ASP454.OD1
65.74%
ASP336.N-SER363.O
65.74%
TYR237.OH-GLN210.OE1
64.97%
MET668.N-THR540.O
64.11%
SER26.OG-ASP163.OD1
63.63%
ARG624.NE-ASP452.OD2
62.96%
VAL130.N-VAL186.O
62.96%
VAL202.N-ILE223.O
62.86%
THR124.OG1-ILE120.O
62.67%
GLN724.NE2-LEU707.O
62.67%
HIS816.N-TYR831.O
62.48%
THR148.OG1-GLU144.O
61.32%
TYR175.OH-TYR787.OH
60.75%
ASN657.ND2-ASN534.O
60.65%
TRP154.NE1-TYR149.O
60.56%
ASN416.ND2-GLY841.O
60.56%
TYR175.N-ILE171.O
60.36%
SER384.OG-MET380.O
59.88%
GLY559.N-GLN541.O
59.88%
ARG305.NH1-GLU474.OE2
59.88%
LYS676.NZ-GLU665.OE1
59.79%
VAL186.N-VAL130.O
59.60%
HIS347.N-GLY327.O
59.50%
ALA400.N-ASN386.O
59.12%
THR604.OG1-ASN600.O
58.64%
ASN416.N-CYS842.O
58.45%
VAL472.N-GLN468.O
58.35%
VAL535.N-ASN356.OD1
58.25%
TYR595.N-TYR915.O
57.97%
ILE185.N-VAL160.O
57.68%
ARG640.NH2-ASP304.OD1
57.68%
THR93.OG1-THR89.O
57.68%
ASN695.ND2-SER759.O
57.49%
LYS577.N-GLN573.O
57.20%
THR870.OG1-TYR867.O
57.20%
TYR674.N-VAL667.O
57.10%
LEU614.N-GLU802.O
57.01%
ASN705.ND2-TYR788.OH
56.91%
ARG654.NH1-THR531.OG1
56.91%
THR248.OG1-ILE244.O
56.72%
THR9.OG1-ASP5.O
56.53%
ILE757.N-THR586.O
56.43%
LYS27.NZ-ASP163.OD2
56.43%
Supplementary Information Table 3.7 The HBs with more than 55% occupancy rates from the analyses of the 1 μs MD trajectory data of SARS-CoV-2 RdRp without template RNA and remdesivir triphosphate [384]
179 Donor-acceptor
Occupancy
ILE132.N-LEU184.O
87.14%
ARG392.NE-ASP390.OD1
83.01%
ILE185.N-VAL160.O
82.44%
ARG392.NH2-ASP390.OD2
81.57%
ALA188.N-LEU128.O
80.33%
VAL186.N-VAL130.O
78.31%
THR540.OG1-GLU665.OE2
77.93%
TRP154.NE1-TYR149.O
77.35%
ARG640.NE-ASP304.OD1
76.97%
LYS676.NZ-GLU665.OE1
76.58%
ARG631.NH2-ASP684.OD2
76.01%
TRP154.N-PHE147.O
76.01%
THR93.OG1-THR89.O
75.62%
GLN157.N-THR187.O
74.95%
ILE156.N-THR145.O
73.70%
LEU128.N-ALA188.O
73.61%
ARG197.NE-TYR289.OH
72.84%
HIP256.ND1-LYS263.O
71.40%
THR89.OG1-SER85.O
70.35%
CYS765.N-SER754.O
69.87%
VAL472.N-GLN468.O
69.77%
SER26.N-ASP163.OD1
69.77%
TYR595.N-TYR915.O
69.77%
TYR674.OH-ASP390.OD2
69.00%
ARG640.NH2-GLU474.OE1
68.71%
ARG640.NH1-GLU474.OE2
68.52%
THR9.OG1-ASP5.O
67.66%
VAL130.N-VAL186.O
67.27%
ARG640.NH2-ASP304.OD2
67.18%
GLU155.N-LEU189.O
66.12%
THR701.OG1-CYS697.O
65.16%
HIS347.N-GLY327.O
64.97%
THR187.N-GLN158.O
64.40%
THR556.OG1-ASP452.OD2
64.20%
GLN724.NE2-LEU707.O
63.72%
TYR237.OH-GLN210.OE1
63.53%
ASN628.ND2-GLU350.OE2
62.96%
PHE92.N-GLN88.O
62.76%
THR556.N-ASP452.OD2
62.00%
SER26.OG-ASP163.OD1
61.80%
LEU189.N-GLU155.O
61.42%
SER384.OG-MET380.O
60.65%
TYR653.OH-HIE355.O
60.36%
CYS142.N-TYR138.O
60.36%
LEU117.N-PRO328.O
60.17%
MET668.N-THR540.O
59.98%
CYS464.N-ASN312.OD1
59.50%
LEU614.N-GLU802.O
59.21%
THR84.OG1-ARG80.O
59.02%
TYR175.OH-TYR787.OH
58.93%
THR248.OG1-ILE244.O
58.73%
ASP336.N-SER363.O
58.64%
ASN416.N-CYS842.O
58.45%
ALA400.N-ASN386.O
58.35%
ASP421.N-LYS417.O
58.16%
VAL535.N-ASN356.OD1
58.06%
TYR787.OH-TYR163.O
57.87%
THR148.OG1-GLU144.O
57.68%
ASN734.N-GLU729.O
57.49%
ALA311.N-ILE307.O
57.29%
THR686.OG1-ASP684.OD1
57.10%
ARG555.NH1-ASP623.OD1
56.81%
TYR175.N-ILE171.O
56.72%
THR531.OG1-PHE528.O
56.62%
LEU469.N-ASP465.O
56.62%
VAL353.N-ASN297.OD1
56.53%
THR137.OG1-ASP134.OD1
56.43%
THR870.OG1-TYR867.O
56.24%
180
3 RNA-Dependent RNA Polymerase (RdRp)
Table 3.8 All the existing SBs from the analyses of the 1 μs MD trajectory data of SARS-CoV-2 RdRp with template RNA and remdesivir triphosphate [384] In MD
-
In opt
-
A:ASP100-A:ARG118
B:ASP101-B:LYS97
A:ASP135-A:LYS780
B:GLU171-B:LYS165
A:ASP100-A:HIS99
B:ASP112-B:ARG111
A:ASP140-A:LYS143
A:ASP100-A:LYS91
B:ASP143-B:LYS139
A:ASP161-A:LYS160
C:ASP38-C:LYS51
A:ASP100-A:LYS98
B:ASP161-B:LYS165
A:ASP170-A:ARG173
C:GLU47-C:LYS43
A:ASP126-A:ARG33
B:ASP163-B:LYS165
A:ASP194-A:ARG197
A:ASP126-A:LYS47
B:ASP78-B:ARG80
A:ASP194-A:LYS288
A:ASP135-A:HIS133
B:ASP78-B:LYS79
A:ASP235-A:ARG467
A:ASP135-A:LYS780
B:ASP78-B:LYS82
A:ASP235-A:ARG735
A:ASP135-A:LYS783
B:ASP99-B:ARG96
A:ASP258-A:LYS263
A:ASP140-A:LYS143
B:GLU171-B:LYS165
A:ASP260-A:LYS263
C:ASP38-C:LYS51
A:ASP291-A:ARG735
A:ASP269-A:LYS272
A:ASP153-A:ARG118 A:ASP154-A:ARG118 A:ASP161-A:LYS160
C:ASP44-C:LYS43
A:ASP304-A:ARG640
A:ASP170-A:ARG173
C:ASP5-C:LYS2
A:ASP304-A:ARG651
A:ASP170-A:LYS159
C:GLU23-C:ARG21
A:ASP358-A:ARG533
A:ASP194-A:ARG197
C:GLU47-C:LYS43
A:ASP390-A:ARG392
A:ASP194-A:LYS288
C:GLU47-C:LYS51
A:ASP40-A:LYS41
A:ASP211-A:ARG118
C:GLU50-C:LYS51
A:ASP418-A:LYS890
A:ASP218-A:ARG118
A:ASP421-A:LYS417
A:ASP218-A:ARG33
A:ASP269-B:ARG111
A:ASP452-A:ARG624
A:ASP218-A:HIS99
A:ASP274-B:ARG111
A:ASP452-A:LYS621
A:ASP218-A:LYS50
A:ASP517-B:ARG80
A:ASP454-A:ARG457
A:ASP221-A:LYS50
A:ASP517-B:LYS79
A:ASP235-A:ARG467
A:ASP523-B:ARG80
A:ASP477-A:ARG640
A:ASP235-A:ARG735
A:GLU277-B:ARG111
A:ASP477-A:LYS641
A:GLU431-C:LYS2
A:ASP484-A:LYS574
A:ASP481-A:LYS478
A:ASP258-A:LYS263 A:ASP260-A:ARG183
A:ASP465-A:ARG132
A:ASP260-A:LYS263
A:GLU431-C:LYS43
A:ASP499-A:ARG513
A:ASP269-A:LYS267
A:GLU436-C:LYS2
A:ASP523-A:LYS369
A:ASP269-A:LYS272
A:GLU436-C:LYS43
A:ASP608-A:LYS751 A:ASP618-A:LYS798 X
A:ASP274-A:LYS272 A:ASP284-A:LYS281
B:ASP99-A:LYS332
A:ASP284-A:LYS288
B:ASP112-A:ARG331
A:ASP684-A:ARG631 A:ASP711-A:LYS714 A:ASP736-A:ARG305
A:ASP291-A:ARG735 A:ASP303-A:ARG651
B:ASP161-C:LYS27
A:ASP804-A:LYS807
A:ASP304-A:ARG640
B:ASP163-C:LYS27
A:ASP825-A:HIS599 X A:ASP833-A:LYS438
A:ASP304-A:ARG651 A:ASP336-A:ARG365 A:ASP358-A:ARG533
C:ASP5-A:LYS430
A:ASP845-A:ARG858 A:ASP846-A:LYS411
A:ASP36-A:LYS50
A:ASP865-A:LYS593
A:ASP390-A:ARG392
A:ASP879-A:HIS882
A:ASP40-A:LYS41
A:ASP879-A:LYS426
A:ASP418-A:LYS417
A:ASP893-A:HIS892
A:ASP418-A:LYS849
A:GLU136-A:LYS783
A:ASP418-A:LYS890
A:GLU144-A:LYS121
A:ASP421-A:LYS417
A:GLU180-A:ARG181
A:ASP452-A:ARG624
A:GLU254-A:ARG183
A:ASP452-A:LYS621
A:GLU254-A:ARG285
A:ASP454-A:ARG457
A:GLU277-A:LYS281
A:ASP465-A:ARG132
A:GLU278-A:LYS281
A:ASP477-A:ARG640
A:GLU350-A:ARG349
A:ASP477-A:LYS478
A:GLU474-A:ARG640
A:ASP477-A:LYS641
A:GLU658-A:ARG631
A:ASP481-A:LYS478
A:GLU658-A:ARG654
A:ASP481-A:LYS641
A:GLU665-A:LYS676
A:ASP484-A:LYS574
A:GLU729-A:HIS725 X
A:ASP499-A:ARG513
A:GLU744-A:ARG726
A:ASP499-A:LYS511
A:GLU796-A:LYS783
A:ASP523-A:LYS369
A:GLU802-A:LYS807
A:ASP608-A:ARG750
A:GLU811-A:LYS798 X
A:ASP608-A:LYS751
A:GLU876-A:LYS430
A:ASP623-A:ARG624
A:GLU894-A:LYS890
A:ASP623-A:LYS621
A:GLU917-A:LYS871
Supplementary Information Table 3.9 All the existing SBs from the analyses of the 1 μs MD trajectory data of SARS-CoV-2 RdRp with template RNA and remdesivir triphosphate [384] (continuation)
181 In MD A:ASP684-A:ARG631 A:ASP711-A:LYS50 A:ASP711-A:LYS714 A:ASP736-A:ARG305 A:ASP738-A:ARG726 A:ASP740-A:ARG726 A:ASP804-A:LYS807 A:ASP824-A:LYS821 A:ASP825-A:LYS603 A:ASP833-A:LYS438 A:ASP845-A:ARG858 A:ASP845-A:LYS411 A:ASP846-A:LYS411 A:ASP846-A:LYS849 A:ASP865-A:LYS593 A:ASP879-A:HIS882 A:ASP879-A:LYS426 A:ASP893-A:ARG889 A:ASP893-A:HIS892 A:ASP893-A:LYS890 A:ASP910-A:ARG914 A:ASP92-A:LYS91 A:ASP92-A:LYS98 A:GLU136-A:LYS143 A:GLU136-A:LYS780 A:GLU136-A:LYS783 A:GLU144-A:ARG118 A:GLU144-A:LYS121 A:GLU144-A:LYS143 A:GLU167-A:LYS159 A:GLU167-A:LYS160 A:GLU167-A:LYS621 A:GLU180-A:ARG181 A:GLU180-A:ARG183 A:GLU254-A:ARG183 A:GLU254-A:ARG285 A:GLU277-A:LYS272 A:GLU277-A:LYS281 A:GLU278-A:LYS272 A:GLU278-A:LYS281 A:GLU350-A:ARG349 A:GLU370-A:LYS369 A:GLU431-A:LYS430 A:GLU436-A:LYS438 A:GLU474-A:ARG305 A:GLU474-A:ARG640 A:GLU610-A:LYS751 A:GLU658-A:ARG631 A:GLU658-A:ARG654 A:GLU665-A:LYS676 A:GLU729-A:ARG733 A:GLU744-A:ARG726 A:GLU796-A:LYS780 A:GLU796-A:LYS783 A:GLU802-A:HIS810 A:GLU802-A:LYS807 A:GLU811-A:HIS810 A:GLU84-A:HIS99 A:GLU84-A:LYS91 A:GLU84-A:LYS98 A:GLU876-A:LYS426 A:GLU876-A:LYS430 A:GLU894-A:LYS890 A:GLU917-A:ARG914 A:GLU917-A:LYS871 A:GLU919-A:ARG583 A:GLU919-A:ARG914
-
In opt
-
182
3 RNA-Dependent RNA Polymerase (RdRp)
Table 3.10 All the existing SBs from the analyses of the 1 μs MD trajectory data of SARS-CoV2 RdRp without template RNA and remdesivir triphosphate [384] In MD
-
In opt
-
A:ASP100-A:ARG118
B:ASP101-B:ARG190
A:ASP135-A:LYS780
B:ASP161-B:LYS165 B:ASP163-B:LYS165
A:ASP100-A:HIS99
B:ASP101-B:LYS97
A:ASP140-A:LYS143
A:ASP100-A:LYS91
B:ASP112-B:ARG111
A:ASP161-A:LYS160
A:ASP100-A:LYS98
B:ASP161-B:LYS165
A:ASP170-A:ARG173
C:ASP38-C:LYS51
A:ASP126-A:ARG33
B:ASP163-B:LYS165
A:ASP194-A:ARG197
C:GLU23-C:ARG21 C:GLU47-C:LYS43
A:ASP126-A:LYS47
B:ASP78-B:ARG80
A:ASP194-A:LYS288
A:ASP135-A:HIS133
B:ASP78-B:LYS79
A:ASP208-A:LYS50
A:ASP135-A:LYS780
B:ASP78-B:LYS82
A:ASP235-A:ARG467
A:ASP135-A:LYS783
B:GLU171-B:LYS165
A:ASP235-A:ARG735
A:ASP140-A:LYS143
C:ASP38-C:LYS51
A:ASP258-A:LYS263
A:ASP143-A:LYS139
C:ASP44-C:LYS43
A:ASP260-A:LYS263
A:ASP161-A:LYS160
C:ASP5-C:LYS2
A:ASP274-A:LYS272
A:ASP170-A:ARG173
C:GLU23-C:ARG21
A:ASP284-A:LYS281
A:ASP170-A:LYS159
C:GLU47-C:LYS43
A:ASP291-A:ARG735
A:ASP194-A:ARG197
C:GLU47-C:LYS51
A:ASP303-A:ARG651
A:ASP194-A:LYS288
C:GLU50-C:LYS51
A:ASP304-A:ARG640
A:ASP208-A:LYS50
D:ASP112-D:ARG111
A:ASP304-A:ARG651
A:ASP211-A:ARG118
D:ASP143-D:LYS139
A:ASP358-A:ARG533
A:ASP218-A:ARG118
D:ASP161-D:LYS165
A:ASP36-A:ARG733
A:ASP218-A:ARG33
D:ASP163-D:LYS127
A:ASP390-A:ARG392
A:ASP218-A:HIS99
D:ASP163-D:LYS165
A:ASP40-A:LYS41
A:ASP218-A:LYS50
D:ASP99-D:ARG96
A:ASP418-A:LYS890 A:ASP421-A:LYS417
A:ASP218-A:LYS98 A:ASP235-A:ARG467
A:ASP274-B:ARG111
A:ASP452-A:ARG624
A:ASP235-A:ARG735
A:ASP517-B:LYS79
A:ASP452-A:LYS621 X
A:ASP258-A:LYS263
A:ASP523-B:ARG80
A:ASP454-A:ARG457
A:ASP260-A:LYS263
A:GLU277-B:ARG111
A:ASP465-A:ARG132
A:GLU431-C:LYS2
A:ASP477-A:LYS641
A:ASP477-A:LYS478
A:ASP269-A:LYS267 A:ASP269-A:LYS272 A:ASP274-A:LYS272
A:GLU431-C:LYS43
A:ASP481-A:LYS478
A:ASP284-A:LYS281
A:GLU436-C:LYS2
A:ASP481-A:LYS641
A:ASP284-A:LYS288
A:GLU436-C:LYS43
A:ASP484-A:LYS577
A:ASP421-D:LYS97
A:ASP618-A:LYS798
A:ASP291-A:ARG467 A:ASP291-A:ARG735 A:ASP303-A:ARG305
A:ASP499-A:ARG513 A:GLU431-D:LYS97
A:ASP623-A:ARG624
B:ASP99-A:LYS332
A:ASP833-A:ARG836
A:ASP304-A:ARG651
B:ASP161-C:LYS27
A:ASP879-A:HIS882
A:ASP336-A:ARG365
B:ASP163-C:LYS27
A:ASP711-A:LYS714
A:ASP303-A:ARG651 A:ASP304-A:ARG305 A:ASP304-A:ARG640
A:ASP845-A:ARG858
A:ASP358-A:ARG533
A:ASP879-A:LYS426 A:ASP893-A:ARG889
B:ASP175-D:LYS127
A:GLU136-A:LYS780
A:ASP40-A:LYS41
C:ASP5-A:LYS430
A:GLU144-A:LYS121
A:ASP418-A:LYS417
C:GLU23-A:LYS411
A:ASP36-A:ARG733
A:GLU136-A:LYS783
A:ASP390-A:ARG392
A:ASP418-A:LYS849 A:ASP418-A:LYS890
C:ASP5-D:LYS97
A:GLU278-A:LYS272
D:ASP99-C:LYS2
A:GLU436-A:LYS438
A:GLU431-A:LYS430
A:ASP421-A:LYS417 A:ASP445-A:ARG553
A:GLU167-A:LYS159 A:GLU254-A:ARG285
A:ASP452-A:ARG553
A:GLU474-A:ARG640
A:ASP452-A:ARG624
A:GLU610-A:LYS751
A:ASP454-A:ARG457
A:GLU658-A:ARG654
A:ASP465-A:ARG132
A:GLU665-A:LYS676
A:ASP477-A:ARG640
A:GLU744-A:ARG726
A:ASP477-A:LYS478
A:GLU796-A:LYS780
A:ASP477-A:LYS641
A:GLU796-A:LYS783
A:ASP481-A:LYS478
A:GLU802-A:LYS807
A:ASP481-A:LYS641
A:GLU811-A:ARG836
A:ASP484-A:LYS574
A:GLU894-A:LYS890
A:ASP484-A:LYS577
A:GLU919-A:ARG583
A:ASP523-B:ARG80 C:GLU23-A:LYS411 D:ASP99-C:LYS2
Supplementary Information Table 3.11 All the existing SBs from the analyses of the 1 μs MD trajectory data of SARS-CoV-2 RdRp without template RNA and remdesivir triphosphate [384] (continuation)
183 In MD
-
In opt
-
A:ASP499-A:ARG513 A:ASP499-A:LYS500 A:ASP499-A:LYS511 A:ASP523-A:LYS369 A:ASP608-A:ARG750 A:ASP608-A:LYS751 A:ASP618-A:LYS621 A:ASP618-A:LYS798 A:ASP623-A:ARG555 A:ASP623-A:ARG624 A:ASP684-A:ARG631 A:ASP711-A:LYS714 A:ASP736-A:ARG305 A:ASP736-A:ARG735 A:ASP738-A:ARG726 A:ASP740-A:ARG726 A:ASP760-A:LYS621 A:ASP761-A:LYS621 A:ASP804-A:LYS807 A:ASP824-A:LYS821 A:ASP833-A:ARG836 A:ASP833-A:HIS439 A:ASP833-A:LYS438 A:ASP845-A:ARG858 A:ASP845-A:LYS411 A:ASP846-A:LYS411 A:ASP846-A:LYS849 A:ASP851-A:LYS511 A:ASP865-A:LYS593 A:ASP879-A:HIS882 A:ASP879-A:LYS426 A:ASP893-A:ARG889 A:ASP893-A:HIS892 A:ASP893-A:LYS890 A:ASP910-A:ARG914 A:ASP92-A:LYS91 A:ASP92-A:LYS98 A:GLU136-A:LYS780 A:GLU136-A:LYS783 A:GLU144-A:ARG118 A:GLU144-A:ARG33 A:GLU144-A:LYS121 A:GLU144-A:LYS143 A:GLU167-A:LYS159 A:GLU167-A:LYS160 A:GLU180-A:ARG183 A:GLU254-A:ARG183 A:GLU254-A:ARG285 A:GLU254-A:LYS281 A:GLU277-A:LYS272 A:GLU277-A:LYS281 A:GLU278-A:LYS272 A:GLU278-A:LYS281 A:GLU350-A:ARG349 A:GLU370-A:LYS369 A:GLU431-A:LYS430 A:GLU436-A:LYS438 A:GLU474-A:ARG305
(continued)
184 Table 3.11 (continued)
3 RNA-Dependent RNA Polymerase (RdRp) In MD A:GLU474-A:ARG640 A:GLU610-A:LYS751 A:GLU658-A:ARG631 A:GLU658-A:ARG654 A:GLU665-A:LYS676 A:GLU729-A:ARG733 A:GLU729-A:HIS725 A:GLU744-A:ARG726 A:GLU796-A:LYS780 A:GLU796-A:LYS783 A:GLU802-A:HIS810 A:GLU802-A:LYS807 A:GLU811-A:ARG836 A:GLU811-A:HIS810 A:GLU811-A:LYS798 A:GLU84-A:HIS99 A:GLU84-A:LYS91 A:GLU84-A:LYS98 A:GLU876-A:LYS426 A:GLU876-A:LYS430 A:GLU894-A:LYS890 A:GLU917-A:ARG914 A:GLU917-A:LYS871 A:GLU919-A:ARG583 A:GLU919-A:ARG914 ASP208-A:ARG33
-
In opt
-
Supplementary Information
185
Table 3.12 The SBs within the RaRp (A-chain) of the peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models in [321] optimized Model peptideA-RdRp
Model peptideB-RdRp
Model peptideC-RdRp
Model peptideAdis-RdRp
Model peptideBdis-RdRp
Model peptideCdis-RdRp
ASP108-ARG6
ASP108-ARG6
ASP108-ARG6
ASP108-ARG6
ASP108-ARG6
ASP108-ARG6
ASP125-ARG357
ASP125-ARG357
ASP125-ARG357
ASP111-ARG623
ASP125-ARG357
ASP125-ARG357
ASP125-ARG625
ASP125-ARG625
ASP125-ARG625
ASP125-ARG357
ASP125-ARG625
ASP125-ARG625
ASP148-LYS153
ASP148-LYS153
ASP148-LYS153
ASP125-ARG625
ASP148-LYS153
ASP148-LYS153
ASP164-LYS162
ASP164-LYS162
ASP164-LYS162
ASP148-LYS153
ASP150-LYS153
ASP150-LYS153
ASP181-ARG625
ASP174-LYS178
ASP174-LYS178
ASP150-LYS153
ASP159-LYS157
ASP159-LYS157
ASP194-ARG530
ASP181-ARG625
ASP181-ARG625
ASP159-LYS157
ASP164-LYS162
ASP164-LYS162
ASP248-ARG423
ASP194-ARG530
ASP194-ARG530
ASP164-LYS162
ASP174-LYS178
ASP174-LYS178
ASP25-LYS673
ASP248-ARG423
ASP194-ARG541
ASP181-ARG625
ASP181-ARG625
ASP181-ARG625
ASP280-ARG282
ASP280-ARG282
ASP248-ARG423
ASP194-ARG530
ASP194-ARG530
ASP194-ARG541
ASP30-LYS33
ASP30-LYS33
ASP280-ARG282
ASP194-ARG541
ASP194-ARG541
ASP248-ARG423
ASP311-LYS307
ASP311-LYS307
ASP30-LYS33
ASP248-ARG423
ASP248-ARG423
ASP25-LYS670
ASP342-ARG443
ASP342-ARG443
ASP311-LYS307
ASP280-ARG282
ASP25-LYS673
ASP280-ARG282
ASP342-ARG514
ASP342-ARG514
ASP342-ARG443
ASP30-LYS33
ASP280-ARG282
ASP308-LYS739
ASP344-ARG347
ASP344-ARG347
ASP342-ARG514
ASP342-ARG443
ASP308-LYS739
ASP30-LYS33
ASP355-ARG22
ASP355-ARG22
ASP344-ARG347
ASP342-LYS511
ASP311-LYS307
ASP311-LYS307
ASP367-LYS368
ASP367-LYS531
ASP355-ARG22
ASP344-ARG347
ASP342-ARG443
ASP342-ARG443
ASP371-LYS368
ASP371-LYS368
ASP367-ARG530
ASP355-ARG22
ASP342-ARG514
ASP342-ARG514
ASP374-LYS464
ASP371-LYS531
ASP371-LYS368
ASP367-ARG530
ASP344-ARG347
ASP344-ARG347
ASP389-ARG403
ASP374-LYS464
ASP371-LYS531
ASP367-LYS531
ASP355-ARG22
ASP355-ARG22
ASP498-LYS641
ASP389-ARG403
ASP374-LYS464
ASP371-LYS368
ASP367-ARG530
ASP367-ARG530
ASP508-LYS441
ASP498-LYS641
ASP389-ARG403
ASP374-LYS464
ASP367-LYS368
ASP367-LYS531
ASP513-ARG443
ASP508-LYS688
ASP498-LYS641
ASP389-ARG403
ASP371-LYS368
ASP371-LYS368
ASP513-ARG514
ASP513-ARG514
ASP508-LYS441
ASP508-LYS688
ASP371-LYS531
ASP374-LYS464
ASP51-LYS50
ASP60-ARG63
ASP513-ARG443
ASP574-LYS390
ASP374-LYS464
ASP389-ARG403
ASP54-LYS688
ASP714-LYS711
ASP513-ARG514
ASP601-LYS604
ASP389-ARG403
ASP498-LYS641
ASP601-LYS604
ASP715-HIS489
ASP51-LYS50
ASP60-ARG63
ASP44-LYS33
ASP513-ARG514
ASP607-LYS608
ASP755-LYS483
ASP601-LYS604
ASP714-LYS711
ASP498-LYS641
ASP54-LYS688
ASP60-ARG63
ASP769-HIS772
ASP60-ARG63
ASP715-LYS493
ASP513-ARG514
ASP60-ARG63
ASP626-ARG195
ASP783-LYS780
ASP626-ARG195
ASP735-ARG748
ASP601-LYS604
ASP626-ARG195
ASP694-LYS697
ASP84-ARG87
ASP714-LYS711
ASP736-LYS301
ASP60-ARG63
ASP694-LYS697
ASP714-LYS711
GLU144-ARG175
ASP715-HIS489
ASP755-LYS483
ASP626-ARG195
ASP714-LYS711
ASP735-ARG748
GLU168-LYS171
ASP735-ARG748
ASP84-ARG87
ASP694-LYS697
ASP715-LYS493
ASP736-LYS301
GLU260-LYS259
ASP755-LYS483
ASP84-LYS178
ASP714-LYS711
ASP735-ARG748
ASP755-LYS483
GLU26-LYS673
ASP769-HIS772
GLU144-ARG175
ASP715-LYS493
ASP736-LYS301
ASP769-HIS772
GLU326-LYS328
ASP783-LYS780
GLU167-LYS162
ASP735-ARG748
ASP755-LYS483
ASP783-LYS780
GLU34-LYS11
ASP84-ARG87
GLU168-LYS171
ASP736-LYS301
ASP769-HIS772
ASP84-LYS178
GLU364-ARG195
ASP84-LYS178
GLU260-LYS259
ASP755-LYS483
ASP783-LYS780
GLU144-ARG175
GLU364-ARG530
GLU144-ARG175
GLU26-LYS670
ASP769-HIS772
ASP84-LYS178
GLU168-LYS171
GLU500-LYS641
GLU168-LYS171
GLU26-LYS673
ASP769-LYS316
GLU144-ARG175
GLU260-LYS259
GLU548-ARG544
GLU260-LYS259
GLU321-LYS320
ASP783-LYS780
GLU167-LYS162
GLU26-LYS673
GLU548-HIS462
GLU26-LYS673
GLU326-LYS328
ASP84-ARG87
GLU168-LYS171
GLU326-LYS328
GLU555-LYS566
GLU326-LYS328
GLU34-LYS11
GLU144-ARG175
GLU260-LYS259
GLU34-LYS11
GLU619-HIS615
GLU34-LYS11
GLU364-ARG195
GLU144-ARG73
GLU26-LYS673
GLU364-ARG195
GLU634-ARG616
GLU364-ARG530
GLU364-ARG530
GLU167-LYS162
GLU321-LYS320
GLU364-ARG530
GLU686-LYS673
GLU500-LYS641
GLU500-HIS642
GLU168-LYS171
GLU326-LYS328
GLU548-ARG544
GLU692-LYS697
GLU548-ARG544
GLU500-LYS641
GLU260-LYS259
GLU34-LYS11
GLU555-LYS566
GLU70-ARG73
GLU555-LYS566
GLU548-ARG521
GLU26-LYS673
GLU364-ARG195
GLU619-HIS615
GLU784-LYS780
GLU619-HIS615
GLU555-LYS566
GLU326-LYS328
GLU364-ARG530
GLU634-ARG616
GLU634-ARG616
GLU57-LYS49
GLU34-LYS11
GLU500-HIS642
GLU686-LYS673
GLU686-LYS673
GLU619-HIS615
GLU364-ARG195
GLU500-LYS641
GLU692-LYS697
GLU692-LYS697
GLU634-ARG616
GLU364-ARG530
GLU548-ARG544
GLU701-LYS441
GLU701-LYS441
GLU686-LYS670
GLU500-HIS642
GLU548-HIS462
GLU70-ARG73
GLU70-ARG73
GLU686-LYS673
GLU548-HIS462
GLU555-LYS566
GLU766-LYS320
GLU784-LYS780
GLU784-LYS780
GLU692-LYS697
GLU555-LYS566
GLU619-HIS615
GLU70-ARG73
GLU619-ARG623
GLU634-ARG616
GLU784-LYS780
GLU634-ARG616
GLU686-LYS673
GLU686-LYS670
GLU692-HIS700
GLU686-LYS673
GLU692-LYS697
GLU692-LYS697
GLU70-ARG73
GLU70-ARG73
GLU784-LYS780
GLU784-LYS780
186
3 RNA-Dependent RNA Polymerase (RdRp)
Table 3.13 The 20 μs MD-SBs within the RaRp (A-chain) of the peptideA-RdRp, peptideBRdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models in [321] Model peptideA-RdRp
Model peptideB-RdRp
Model peptideC-RdRp
Model peptideAdis-RdRp
Model peptideBdis-RdRp
Model peptideCdis-RdRp
ASP101-ARG6
ASP101-LYS11
ASP101-ARG8
ASP101-ARG8
ASP101-ARG6
ASP101-ARG6
ASP101-ARG8
ASP108-ARG6
ASP101-LYS11
ASP101-LYS11
ASP101-ARG8
ASP101-ARG8
ASP101-LYS11
ASP108-ARG8
ASP108-ARG6
ASP108-ARG6
ASP101-LYS11
ASP101-LYS11
ASP108-ARG6
ASP111-ARG623
ASP108-ARG8
ASP108-ARG8
ASP108-ARG6
ASP108-ARG6
ASP108-ARG8
ASP125-ARG357
ASP111-ARG6
ASP111-ARG623
ASP108-ARG8
ASP108-ARG8
ASP125-ARG357
ASP125-ARG623
ASP111-ARG623
ASP125-ARG357
ASP111-ARG8
ASP125-ARG357
ASP125-ARG623
ASP125-ARG625
ASP125-ARG357
ASP125-ARG623
ASP125-ARG357
ASP125-ARG623
ASP125-ARG625
ASP148-ARG139
ASP125-ARG623
ASP125-ARG625
ASP125-ARG623
ASP125-ARG625
ASP148-ARG63
ASP148-ARG175
ASP125-ARG625
ASP148-ARG139
ASP125-ARG625
ASP148-LYS153
ASP148-LYS153
ASP148-ARG282
ASP148-ARG139
ASP148-ARG175
ASP148-LYS153
ASP150-LYS153
ASP148-LYS157
ASP148-ARG63
ASP148-ARG282
ASP148-ARG63
ASP150-LYS153
ASP159-ARG282
ASP150-LYS153
ASP148-LYS153
ASP148-LYS153
ASP148-LYS153
ASP159-LYS162
ASP159-LYS157
ASP159-ARG221
ASP148-LYS157
ASP148-LYS171
ASP148-LYS157
ASP164-ARG221
ASP159-LYS162
ASP159-LYS157
ASP148-LYS171
ASP148-LYS281
ASP150-ARG175
ASP164-LYS162
ASP159-LYS281
ASP159-LYS162
ASP150-ARG282
ASP150-ARG282
ASP150-ARG63
ASP16-ARG8
ASP164-LYS162
ASP159-LYS222
ASP150-LYS153
ASP150-LYS153
ASP150-LYS153
ASP174-LYS171
ASP174-LYS171
ASP164-LYS162
ASP159-ARG221
ASP150-LYS281
ASP159-ARG221
ASP174-LYS178
ASP174-LYS178
ASP174-LYS171
ASP159-ARG282
ASP159-ARG221
ASP159-LYS153
ASP181-ARG357
ASP181-ARG357
ASP174-LYS178
ASP159-LYS157
ASP159-ARG282
ASP159-LYS157
ASP181-ARG625
ASP181-ARG625
ASP181-ARG357
ASP159-LYS162
ASP159-LYS162
ASP159-LYS162
ASP193-ARG195
ASP193-ARG195
ASP181-ARG625
ASP159-LYS222
ASP164-LYS162
ASP159-LYS222
ASP194-ARG195
ASP194-ARG530
ASP193-ARG195
ASP164-ARG169
ASP174-LYS171
ASP164-LYS157
ASP194-ARG530
ASP248-ARG423
ASP193-ARG541
ASP164-LYS162
ASP174-LYS178
ASP164-LYS162
ASP194-ARG541
ASP25-LYS670
ASP194-ARG195
ASP174-LYS171
ASP181-ARG357
ASP174-ARG175
ASP226-ARG255
ASP25-LYS673
ASP194-ARG530
ASP174-LYS178
ASP181-ARG625
ASP174-LYS171
ASP248-ARG423
ASP280-ARG282
ASP194-ARG541
ASP181-ARG357
ASP193-ARG195
ASP174-LYS178
ASP25-LYS670
ASP280-LYS157
ASP226-ARG255
ASP181-ARG625
ASP194-ARG530
ASP181-ARG195
ASP25-LYS673
ASP280-LYS281
ASP226-ARG282
ASP193-ARG195
ASP226-ARG255
ASP181-ARG357
ASP267-ARG255
ASP308-LYS739
ASP248-ARG221
ASP194-ARG195
ASP226-ARG403
ASP181-ARG625
ASP280-ARG282
ASP30-LYS33
ASP248-ARG255
ASP194-ARG530
ASP248-ARG423
ASP193-ARG195
ASP308-LYS307
ASP311-LYS307
ASP248-ARG423
ASP248-ARG423
ASP25-LYS670
ASP194-ARG195
ASP308-LYS739
ASP335-ARG726
ASP25-LYS670
ASP25-LYS670
ASP25-LYS673
ASP194-ARG530
ASP308-LYS780
ASP335-LYS301
ASP25-LYS673
ASP25-LYS673
ASP280-ARG282
ASP194-ARG541
ASP30-LYS33
ASP335-LYS307
ASP267-ARG255
ASP267-ARG255
ASP280-LYS157
ASP226-ARG255
ASP311-LYS307
ASP335-LYS435
ASP267-LYS398
ASP280-ARG282
ASP280-LYS222
ASP248-ARG423
ASP335-ARG443
ASP342-ARG443
ASP280-ARG255
ASP280-LYS162
ASP280-LYS281
ASP25-LYS670
ASP335-ARG445
ASP342-ARG445
ASP280-ARG282
ASP280-LYS222
ASP308-LYS307
ASP25-LYS673
ASP342-ARG443
ASP342-ARG514
ASP280-ARG347
ASP280-LYS281
ASP308-LYS739
ASP267-ARG282
ASP342-ARG445
ASP342-LYS511
ASP280-ARG445
ASP308-LYS307
ASP30-LYS33
ASP267-LYS398
ASP342-ARG514
ASP344-ARG347
ASP280-LYS281
ASP308-LYS739
ASP311-LYS307
ASP280-ARG282
ASP342-LYS511
ASP344-ARG443
ASP280-LYS441
ASP308-LYS780
ASP335-ARG445
ASP280-LYS281
ASP344-ARG282
ASP344-ARG514
ASP308-LYS307
ASP30-ARG6
ASP335-LYS301
ASP308-LYS307
ASP344-ARG347
ASP344-LYS511
ASP308-LYS739
ASP30-LYS33
ASP335-LYS398
ASP308-LYS780
ASP344-LYS511
ASP355-ARG22
ASP308-LYS780
ASP311-LYS307
ASP342-ARG347
ASP30-LYS33
ASP355-ARG22
ASP367-ARG530
ASP30-LYS33
ASP335-ARG443
ASP342-ARG443
ASP311-LYS307
ASP367-ARG530
ASP367-LYS368
ASP311-LYS307
ASP335-LYS301
ASP342-ARG445
ASP335-ARG443
ASP367-LYS368
ASP367-LYS531
ASP311-LYS328
ASP335-LYS441
ASP342-ARG514
ASP335-LYS328
ASP367-LYS531
ASP371-LYS368
ASP335-ARG282
ASP335-LYS566
ASP342-LYS328
ASP342-ARG443
ASP371-LYS368
ASP371-LYS531
ASP335-ARG347
ASP342-ARG347
ASP342-LYS441
ASP342-ARG445
ASP371-LYS531
ASP374-LYS464
ASP335-ARG443
ASP342-ARG443
ASP342-LYS511
ASP342-ARG514
ASP374-ARG473
ASP389-ARG403
ASP335-ARG445
ASP342-ARG514
ASP344-ARG282
ASP342-LYS441
ASP374-LYS464
ASP389-ARG459
ASP335-ARG726
ASP342-LYS301
ASP344-ARG347
ASP342-LYS511
ASP389-ARG403
ASP389-LYS401
ASP335-LYS301
ASP344-ARG347
ASP344-ARG445
ASP344-ARG347
ASP389-ARG459
ASP389-LYS711
ASP335-LYS328
ASP355-ARG22
ASP344-LYS566
ASP344-ARG445
ASP389-LYS390
ASP407-ARG403 ASP407-ARG459
ASP335-LYS483
ASP367-ARG530
ASP355-ARG22
ASP344-ARG514
ASP389-LYS401
ASP335-LYS566
ASP367-LYS368
ASP367-ARG530
ASP344-LYS566
ASP407-ARG403
ASP407-LYS390
ASP342-ARG282
ASP367-LYS531
ASP367-LYS531
ASP355-ARG22
ASP413-LYS259
ASP407-LYS401
ASP342-ARG347
ASP371-LYS368
ASP371-ARG530
ASP367-ARG530
ASP43-ARG6
ASP413-LYS259
ASP342-ARG443
ASP371-LYS531
ASP371-LYS368
ASP367-LYS531
ASP43-ARG63
ASP43-ARG63
ASP342-ARG445
ASP374-ARG473
ASP371-LYS531
ASP371-LYS368
ASP44-LYS33
ASP45-LYS49
ASP342-ARG514
ASP374-LYS464
ASP374-LYS464
ASP371-LYS531
ASP498-ARG640
ASP498-ARG640
ASP342-LYS281
ASP389-ARG403
ASP389-ARG403
ASP374-LYS464
ASP498-LYS641
ASP498-LYS641
(continued)
Supplementary Information
187
Table 3.13 (continued) Model peptideA-RdRp
Model peptideB-RdRp
Model peptideC-RdRp
Model peptideAdis-RdRp
Model peptideBdis-RdRp
Model peptideCdis-RdRp
ASP342-LYS301
ASP389-ARG459
ASP389-ARG459
ASP389-ARG403
ASP508-LYS688
ASP508-LYS688
ASP342-LYS441
ASP389-LYS259
ASP389-LYS301
ASP389-ARG459
ASP513-ARG445
ASP513-ARG347
ASP342-LYS511
ASP389-LYS301
ASP389-LYS390
ASP389-LYS390
ASP513-ARG514
ASP513-ARG443
ASP344-ARG282
ASP389-LYS390
ASP389-LYS401
ASP389-LYS401
ASP51-LYS50
ASP513-ARG445
ASP344-ARG347
ASP389-LYS401
ASP389-LYS435
ASP389-LYS435
ASP574-ARG445
ASP513-ARG514
ASP344-ARG443
ASP407-ARG255
ASP407-ARG403
ASP389-LYS739
ASP574-ARG459
ASP513-LYS441
ASP344-ARG445
ASP407-ARG403
ASP407-LYS259
ASP407-ARG403
ASP574-LYS390
ASP513-LYS511
ASP344-ARG514
ASP407-LYS259
ASP407-LYS390
ASP413-LYS259
ASP574-LYS435
ASP513-LYS688
ASP344-LYS281
ASP413-LYS259
ASP413-LYS259
ASP43-ARG63
ASP601-LYS604
ASP51-LYS50
ASP344-LYS441
ASP415-LYS398
ASP43-ARG63
ASP44-ARG6
ASP60-ARG63
ASP574-LYS390
ASP344-LYS566
ASP43-ARG6
ASP45-LYS49
ASP45-LYS49
ASP60-LYS49
ASP574-LYS467
ASP355-ARG22
ASP43-ARG8
ASP498-ARG640
ASP498-ARG640
ASP626-ARG195
ASP574-LYS483
ASP367-ARG530
ASP43-LYS49
ASP498-LYS641
ASP498-LYS641
ASP626-ARG625
ASP601-LYS604
ASP367-LYS531
ASP44-ARG6
ASP508-LYS441
ASP508-ARG514
ASP628-ARG616
ASP60-ARG63
ASP371-LYS368
ASP44-ARG8
ASP508-LYS688
ASP508-LYS511
ASP630-ARG616
ASP60-LYS49
ASP374-ARG473
ASP45-ARG6
ASP513-ARG347
ASP508-LYS688
ASP650-ARG445
ASP626-ARG195
ASP374-LYS464
ASP45-LYS33
ASP513-ARG443
ASP513-ARG347
ASP650-ARG514
ASP626-ARG625
ASP389-ARG403
ASP498-ARG473
ASP513-ARG445
ASP513-ARG443
ASP650-LYS511
ASP628-ARG616
ASP389-ARG445
ASP498-ARG640
ASP513-ARG514
ASP513-ARG445
ASP651-ARG514
ASP630-ARG616
ASP389-ARG459
ASP508-ARG443
ASP513-LYS511
ASP513-ARG514
ASP694-LYS697
ASP650-ARG514
ASP389-LYS390
ASP508-LYS441
ASP513-LYS566
ASP513-LYS441
ASP714-LYS711
ASP650-LYS441
ASP389-LYS401
ASP508-LYS688
ASP51-LYS50
ASP513-LYS688
ASP715-LYS493
ASP650-LYS483
ASP407-ARG403
ASP513-ARG443
ASP574-ARG459
ASP51-LYS50
ASP723-ARG726
ASP650-LYS511
ASP407-LYS390
ASP513-ARG445
ASP574-ARG521
ASP54-ARG347
ASP723-LYS328
ASP651-LYS483
ASP413-ARG255
ASP513-ARG514
ASP601-LYS604
ASP574-ARG445
ASP723-LYS441
ASP694-LYS697
ASP413-LYS259
ASP513-LYS511
ASP60-ARG63
ASP574-ARG459
ASP735-ARG748
ASP714-LYS401
ASP43-ARG6
ASP513-LYS566
ASP60-LYS49
ASP574-LYS390
ASP735-LYS301
ASP714-LYS467
ASP43-ARG63
ASP51-LYS441
ASP626-ARG195
ASP574-LYS435
ASP735-LYS390
ASP714-LYS711
ASP44-ARG6
ASP51-LYS50
ASP626-ARG625
ASP601-LYS604
ASP735-LYS401
ASP715-ARG403
ASP45-LYS49
ASP51-LYS673
ASP628-ARG616
ASP60-ARG63
ASP736-ARG748
ASP715-ARG473
ASP498-ARG640
ASP54-ARG443
ASP630-ARG616
ASP60-LYS49
ASP736-LYS301
ASP715-LYS390
ASP498-LYS641
ASP574-ARG445
ASP650-ARG443
ASP626-ARG195
ASP736-LYS390
ASP715-LYS401
ASP508-ARG443
ASP574-ARG459
ASP650-ARG445
ASP626-ARG625
ASP736-LYS739
ASP715-LYS467
ASP508-ARG514
ASP574-LYS390
ASP650-LYS441
ASP628-ARG616
ASP741-LYS739
ASP723-ARG726
ASP508-LYS441
ASP601-LYS604
ASP650-LYS511
ASP630-ARG616
ASP755-ARG726
ASP723-LYS328
ASP508-LYS511
ASP60-ARG63
ASP651-ARG443
ASP650-ARG445
ASP755-ARG748
ASP735-ARG748
ASP508-LYS688
ASP60-LYS49
ASP651-LYS441
ASP650-ARG514
ASP755-LYS483
ASP735-LYS301
ASP513-ARG347
ASP626-ARG195
ASP694-LYS697
ASP650-LYS441
ASP783-ARG779
ASP735-LYS435
188
3 RNA-Dependent RNA Polymerase (RdRp)
Table 3.14 The 20 μs MD-SBs within the RaRp (A-chain) of the peptideA-RdRp, peptideBRdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models in [321] (continuation) Model peptideA-RdRp
Model peptideB-RdRp
Model peptideC-RdRp
Model peptideAdis-RdRp
Model peptideBdis-RdRp
Model peptideCdis-RdRp
ASP513-ARG443
ASP626-ARG625
ASP714-LYS467
ASP650-LYS511
ASP783-LYS780
ASP735-LYS739
ASP513-ARG445
ASP628-ARG616
ASP714-LYS711
ASP651-ARG514
ASP84-ARG87
ASP736-ARG748
ASP513-ARG514
ASP630-ARG616
ASP715-LYS467
ASP694-LYS697
ASP84-LYS178
ASP736-LYS301
ASP513-ARG521
ASP650-ARG443
ASP715-LYS483
ASP714-LYS711
GLU144-ARG175
ASP736-LYS398
ASP513-LYS511
ASP650-ARG445
ASP723-ARG443
ASP723-ARG726
GLU144-ARG73
ASP736-LYS739
ASP513-LYS566
ASP650-LYS441
ASP723-ARG726
ASP723-LYS441
GLU167-LYS162
ASP741-LYS739
ASP51-LYS50
ASP650-LYS483
ASP723-LYS328
ASP735-ARG748
GLU167-LYS171
ASP755-ARG726
ASP574-ARG459
ASP650-LYS511
ASP723-LYS441
ASP735-LYS301
GLU168-ARG175
ASP755-ARG748
ASP574-ARG521
ASP651-ARG443
ASP735-ARG445
ASP735-LYS435
GLU168-LYS162
ASP755-LYS398
ASP601-LYS604
ASP651-LYS441
ASP735-ARG748
ASP736-ARG748
GLU168-LYS171
ASP755-LYS401
ASP60-ARG63
ASP651-LYS483
ASP735-LYS301
ASP736-LYS301
GLU240-ARG239
ASP755-LYS483
ASP60-LYS49
ASP651-LYS688
ASP736-ARG445
ASP736-LYS390
GLU260-ARG255
ASP783-ARG779
ASP626-ARG195
ASP694-LYS697
ASP736-ARG748
ASP736-LYS435
GLU260-LYS259
ASP783-LYS780
ASP626-ARG625
ASP714-ARG459
ASP736-LYS301
ASP741-LYS739
GLU26-LYS33
ASP84-ARG87
ASP628-ARG616
ASP714-LYS467
ASP736-LYS739
ASP755-ARG726
GLU26-LYS670
ASP84-LYS178
ASP630-ARG616
ASP714-LYS711
ASP741-LYS401
ASP755-ARG748
GLU26-LYS673
ASP98-ARG8
ASP650-ARG443
ASP715-LYS467
ASP741-LYS739
ASP755-LYS483
GLU326-ARG443
GLU144-ARG175
ASP650-ARG445
ASP715-LYS483
ASP755-ARG748
ASP783-ARG779
GLU326-ARG726
GLU144-ARG73
ASP650-LYS511
ASP715-LYS493
ASP755-LYS483
ASP783-LYS780
GLU326-LYS328
GLU167-LYS162
ASP651-ARG443
ASP723-ARG726
ASP783-ARG779
ASP84-ARG175
GLU326-LYS441
GLU167-LYS171
ASP651-LYS483
ASP723-LYS328
ASP783-LYS780
ASP84-ARG87
GLU34-ARG6
GLU168-ARG175
ASP651-LYS511
ASP735-ARG445
ASP84-ARG175
ASP84-LYS178
GLU34-ARG8
GLU168-LYS162
ASP694-LYS697
ASP735-ARG748
ASP84-ARG87
GLU144-ARG139
GLU34-LYS11
GLU168-LYS171
ASP714-LYS711
ASP735-LYS435
ASP84-LYS178
GLU144-ARG175
GLU34-LYS33
GLU240-ARG239
ASP723-ARG726
ASP736-ARG748
GLU144-ARG139
GLU144-ARG63
GLU364-ARG195
GLU260-ARG255
ASP735-ARG445
ASP736-LYS301
GLU144-ARG175
GLU144-ARG73
GLU364-ARG530
GLU260-LYS259
ASP735-ARG748
ASP736-LYS435
GLU144-ARG63
GLU144-LYS153
GLU500-LYS641
GLU26-LYS670
ASP735-LYS301
ASP736-LYS739
GLU144-ARG71
GLU144-LYS171
GLU548-ARG521
GLU26-LYS673
ASP735-LYS435
ASP741-ARG748
GLU144-ARG73
GLU167-LYS153
GLU548-ARG544
GLU321-LYS320
ASP735-LYS441
ASP741-LYS401
GLU167-LYS153
GLU167-LYS157
GLU555-LYS566
GLU321-LYS328
ASP735-LYS739
ASP741-LYS739
GLU167-LYS162
GLU167-LYS162
GLU57-ARG347
GLU321-LYS441
ASP736-ARG443
ASP755-ARG726
GLU167-LYS171
GLU167-LYS171
GLU57-LYS49
GLU326-LYS307
ASP736-ARG445
ASP755-ARG748
GLU168-ARG169
GLU168-LYS153
GLU619-ARG616
GLU326-LYS320
ASP736-ARG748
ASP755-LYS483
GLU168-LYS162
GLU168-LYS157
GLU634-ARG616
GLU326-LYS328
ASP736-LYS301
ASP783-ARG779
GLU168-LYS171
GLU168-LYS162
GLU686-LYS670
GLU326-LYS441
ASP736-LYS441
ASP783-LYS401
GLU240-ARG239
GLU168-LYS171
GLU686-LYS673
GLU34-ARG6
ASP736-LYS739
ASP783-LYS780
GLU260-ARG221
GLU240-ARG239
GLU692-LYS697
GLU34-ARG8
ASP741-ARG443
ASP84-ARG175
GLU260-ARG255
GLU260-ARG255
GLU701-LYS441
GLU34-LYS11
ASP741-LYS301
ASP84-ARG87
GLU260-LYS259
GLU26-LYS670
GLU70-ARG71
GLU364-ARG195
ASP741-LYS739
ASP84-LYS178
GLU26-LYS50
GLU26-LYS673
GLU70-ARG73
GLU364-ARG530
ASP755-LYS483
GLU144-ARG175
GLU26-LYS673
GLU321-LYS320
GLU747-ARG403
GLU412-LYS259
ASP783-ARG779
GLU144-ARG73
GLU321-ARG443
GLU321-LYS328
GLU784-LYS780
GLU500-LYS641
ASP783-LYS780
GLU167-LYS162
GLU321-ARG445
GLU326-ARG726
GLU548-ARG521
ASP84-ARG175
GLU167-LYS171
GLU321-ARG514
GLU326-LYS301
GLU548-ARG544
ASP84-ARG87
GLU168-LYS153
GLU321-LYS328
GLU326-LYS307
GLU555-LYS566
ASP84-LYS178
GLU168-LYS162
GLU321-LYS441
GLU326-LYS320
GLU57-ARG347
GLU144-ARG139
GLU168-LYS171
GLU321-LYS511
GLU326-LYS328
GLU57-ARG443
GLU144-ARG175
GLU240-ARG239
GLU326-ARG443
GLU34-ARG6
GLU57-ARG514
GLU144-ARG63
GLU260-ARG255
GLU326-ARG445
GLU34-ARG8
GLU57-LYS441
GLU144-ARG73
GLU260-LYS259
GLU326-LYS328
GLU34-LYS11
GLU57-LYS511
GLU144-LYS153
GLU26-LYS670
GLU326-LYS441
GLU364-ARG195
GLU619-ARG616
GLU144-LYS171
GLU26-LYS673
GLU326-LYS511
GLU364-ARG530
GLU634-ARG616
GLU167-LYS157
GLU321-LYS328
GLU34-ARG6
GLU412-LYS259
GLU686-LYS50
GLU167-LYS162
GLU326-ARG726
GLU34-ARG8
GLU500-LYS641
GLU686-LYS670
GLU167-LYS171
GLU326-LYS328
GLU34-LYS11
GLU548-ARG521
GLU686-LYS673
GLU168-ARG169
GLU34-ARG6
GLU364-ARG195
GLU548-ARG544
GLU686-LYS688
GLU168-ARG175
GLU34-ARG8
GLU364-ARG530
GLU555-ARG347
GLU692-LYS697
GLU168-LYS162
GLU34-LYS11
GLU412-ARG403
GLU555-ARG514
GLU701-ARG726
GLU168-LYS171
GLU364-ARG195
GLU412-LYS259
GLU555-LYS566
GLU701-LYS328
GLU240-ARG239
GLU364-ARG530
GLU412-LYS390
GLU57-ARG347
GLU701-LYS483
GLU260-ARG255
GLU412-LYS398
GLU500-LYS641
GLU57-LYS49
GLU701-LYS688
GLU260-LYS259
GLU500-LYS641
GLU548-ARG521
GLU57-LYS50
GLU701-LYS697
GLU26-LYS50
GLU548-ARG521
GLU548-ARG544
GLU619-ARG616
GLU70-ARG6
(continued)
Supplementary Information
189
Table 3.14 (continued) Model peptideA-RdRp
Model peptideB-RdRp
Model peptideC-RdRp
Model peptideAdis-RdRp
GLU26-LYS670
GLU548-ARG541
GLU555-LYS566
GLU634-ARG616
Model peptideBdis-RdRp
GLU70-ARG71
Model peptideCdis-RdRp GLU70-ARG73
GLU26-LYS673
GLU548-ARG544
GLU57-ARG514
GLU686-LYS511
GLU321-ARG726
GLU555-LYS566
GLU57-LYS441
GLU686-LYS670
GLU747-ARG403
GLU326-ARG726
GLU57-ARG443
GLU57-LYS511
GLU686-LYS673
GLU747-ARG748
GLU326-LYS328
GLU57-ARG514
GLU619-ARG616
GLU686-LYS688
GLU747-LYS390
GLU326-LYS441
GLU57-LYS441
GLU634-ARG616
GLU692-LYS697
GLU747-LYS401
GLU34-ARG6
GLU57-LYS49
GLU686-LYS670
GLU701-ARG726
GLU747-LYS739
GLU34-ARG8
GLU619-ARG616
GLU686-LYS673
GLU70-ARG63
GLU784-ARG779
GLU34-LYS11
GLU619-ARG623
GLU692-LYS697
GLU70-ARG71
GLU784-LYS780
GLU364-ARG195
GLU634-ARG616
GLU701-ARG443
GLU70-ARG73
GLU364-ARG530
GLU686-LYS50
GLU701-LYS441
GLU747-ARG748
GLU412-ARG255
GLU686-LYS670
GLU701-LYS483
GLU747-LYS739
GLU412-LYS259
GLU686-LYS673
GLU701-LYS697
GLU784-ARG779 GLU784-LYS780
GLU500-LYS641
GLU692-LYS697
GLU70-ARG6
GLU548-ARG521
GLU701-ARG726
GLU70-ARG63
GLU548-ARG544
GLU701-LYS688
GLU70-ARG71
GLU555-ARG347
GLU701-LYS697
GLU70-ARG73
GLU555-ARG443
GLU70-ARG63
GLU766-LYS435
GLU555-ARG445
GLU70-ARG71
GLU784-ARG779
GLU555-LYS441
GLU70-ARG73
GLU784-LYS780
GLU555-LYS566
GLU747-ARG459
GLU57-ARG347
GLU747-ARG748
GLU57-LYS441
GLU747-LYS390
GLU619-ARG616
GLU747-LYS401
GLU619-ARG623
GLU747-LYS483
GLU634-ARG616
GLU766-LYS320
GLU686-LYS670
GLU784-ARG779
GLU686-LYS673
GLU784-LYS780
GLU692-LYS697 GLU701-ARG726 GLU701-LYS328 GLU70-ARG63 GLU70-ARG71 GLU70-ARG73 GLU747-LYS739 GLU784-ARG779 GLU784-LYS739 GLU784-LYS780
CYS620.N-ARG616.O 60.70 ALA667.N-ASN593.OD1 60.20
VAL654.N-MET505.O 63.68
ALA667.N-ASN593.OD1 63.18
VAL366.N-VAL362.O 63.18
CYS620.N-ARG616.O 63.18
TYR677.OH-TYR53.O 63.18
TYR127.OH-GLN100.OE1 62.69
ARG616.N-ASN612.O 62.19
PHE635.N-PHE631.O 61.69
LYS673.N-ILE669.O 61.69
LEU676.N-PHE672.O 61.69
ALA313.N-PHE309.O 61.69
TYR184.OH-ASN204.OD1 61.19
LEU359.N-ASP355.O 61.19
ASN306.N-CYS732.O 60.70
ALA201.N-ILE197.O 60.70
VAL366.N-VAL362.O 64.18
LYS673.N-ILE669.O 63.68
ARG73.N-GLY69.O 63.68
TYR127.OH-GLN100.OE1 63.18
ALA667.N-ASN593.OD1 63.18
LEU359.N-ASP355.O 62.69
TYR677.OH-TYR53.O 62.69
CYS200.N-CYX196.O 62.19
VAL314.N-TYR310.O 62.19
TYR767.OH-PRO722.O 62.19
CYS620.N-ARG616.O 61.69
THR38.OG1-GLU34.O 60.70
LEU676.N-PHE672.O 60.70
ARG640.N-TYR636.O 58.71
LEU728.N-PRO724.O 58.71
ALA546.N-PHE542.O 65.67
LEU359.N-ASP355.O 64.68
TYR127.OH-GLN100.OE1 55.72
VAL362.N-GLN358.O 57.71
ASN581.N-THR577.O 58.21
ASN204.N-CYS200.O 57.71
ARG640.N-TYR636.O 57.71
ILE223.N-PHE230.O 57.21
THR138.OG1-ILE134.O 57.21
ARG73.N-GLY69.O 56.72
MET523.N-MET519.O 55.72
VAL363.N-LEU359.O 55.22
HID237.N-GLY217.O 55.22
PHE230.N-ILE223.O 54.73
LEU781.N-TYR777.O 54.73
ASN595.N-THR591.O 54.23
TYR65.N-ILE61.O 54.23
MET86.N-PHE82.O 53.73
VAL590.N-ILE586.O 53.73
CYS354.N-ASN202.OD1 57.21
ASN306.N-CYS732.O 57.21
MET456.N-ILE452.O 56.22
ASN397.N-GLY393.O 55.72
TYR184.OH-ASN204.OD1 55.22
LEU781.N-TYR777.O 55.22
LEU76.N-VAL72.O 55.22
CYS587.N-VAL583.O 54.73
VAL750.N-ILE746.O 54.23
THR138.OG1-ILE134.O 54.23
CYS655.N-SER644.O 53.73
ALA201.N-ILE197.O 53.73
VAL717.N-VAL710.O 53.73
ALA592.N-GLN588.O 53.23
TYR65.OH-TYR677.OH 53.23
VAL362.N-GLN358.O 58.71
VAL750.N-ILE746.O 58.21
ALA546.N-PHE542.O 58.21
TYR622.OH-ASP355.OD2 57.21
ASN306.N-CYS732.O 55.72
THR136.OG1-PRO351.O 58.21
VAL425.N-ASN246.OD1 59.20
LYS531.NZ-TYR373.O 59.20
ASP415.N-TYR411.O 58.21
MET86.N-PHE82.O 53.23
ARG640.N-TYR636.O 53.73
ASN306.N-CYS732.O 53.73
ASP311.N-LYS307.O 54.23
ILE647.N-THR476.O 54.73
LEU492.N-TRP488.O 55.72
VAL717.N-VAL710.O 55.72
VAL750.N-ILE746.O 55.72
ASN58.N-ASP54.O 55.72
ASN518.ND2-GLU240.OE2 56.22
VAL366.N-VAL362.O 56.72
THR591.OG1-CYS587.O 56.72
TYR127.OH-GLN100.OE1 56.72
CYS354.N-ASN202.OD1 57.21
ALA592.N-GLN588.O 57.21
ASN595.N-THR591.O 57.21
LEU359.N-ASP355.O 59.70
THR591.OG1-CYS587.O 57.71
MET86.N-PHE82.O 52.24
THR138.OG1-ILE134.O 52.74
ASN547.N-TYR543.O 53.23
ILE778.N-TYR774.O 53.23
ALA201.N-ILE197.O 53.23
CYS83.N-THR79.O 53.23
LEU198.N-ASP194.O 53.73
GLN679.N-VAL675.O 53.73
VAL590.N-ILE586.O 53.73
VAL717.N-VAL710.O 54.23
LEU219.N-GLY235.O 54.23
LEU76.N-VAL72.O 54.73
ARG640.N-TYR636.O 54.73
TYR677.OH-TYR53.O 55.22
TYR184.OH-ASN204.OD1 55.22
LYS673.N-ILE669.O 55.72
VAL750.N-ILE746.O 55.72
ALA546.N-PHE542.O 57.71
TYR19.N-ALA15.O 58.21
TYR184.OH-ASN204.OD1 59.70
ALA546.N-PHE542.O 60.20
CYS655.N-SER644.O 59.70
MET558.N-THR430.O 58.71
ILE426.N-ASN547.OD1 58.21
ALA313.N-PHE309.O 58.21
CYS354.N-ASN202.OD1 58.21
CYS655.N-SER644.O 58.21
VAL425.N-ASN246.OD1 58.71
THR136.OG1-PRO351.O 58.71
LEU676.N-PHE672.O 58.71
ARG73.N-GLY69.O 58.71
VAL366.N-VAL362.O 59.20
CYS620.N-ARG616.O 60.20
CYS200.N-CYX196.O 60.70
VAL363.N-LEU359.O 61.19
SER668.N-ASN671.OD1 61.69
ARG616.N-ASN612.O 61.69
ALA667.N-ASN593.OD1 62.19
TYR19.N-ALA15.O 62.69
TYR543.OH-HID245.O 63.68
PHE635.N-PHE631.O 64.18
THR591.OG1-CYS587.O 58.71
VAL654.N-MET505.O 60.70
ARG73.N-GLY69.O 60.70
THR591.N-CYS587.O 61.19
ASN581.N-THR577.O 61.69
LEU781.N-TYR777.O 62.19
ALA201.N-ILE197.O 62.19
ARG616.N-ASN612.O 62.69
TYR543.OH-HID245.O 62.69
PHE635.N-PHE631.O 62.69
CYS200.N-CYX196.O 62.69
ALA313.N-PHE309.O 63.18
VAL363.N-LEU359.O 63.18
ASN547.N-TYR543.O 64.18
TYR767.OH-PRO722.O 64.68
PHE584.N-ALA580.O 64.68
VAL314.N-TYR310.O 65.17
TYR543.OH-HID245.O 64.18
THR136.OG1-PRO351.O 65.17
VAL590.N-ILE586.O 64.18
VAL425.N-ASN246.OD1 66.67
TYR19.N-ALA15.O 67.16
CYS200.N-CYX196.O 66.17
TYR19.N-ALA15.O 65.67
PHE635.N-PHE631.O 68.16
GLN588.N-PHE584.O 70.15
ALA313.N-PHE309.O 65.17
Model peptideAdis-RdRp ASN397.N-GLY393.O 66.67
Model peptideC-RdRp
Model peptideB-RdRp
CYS354.N-ASN202.OD1 71.14
Model peptideA-RdRp
ARG616.N-ASN612.O 69.15
LEU781.N-TYR777.O 52.74
MET558.N-THR430.O 52.74
VAL590.N-ILE586.O 52.74
ARG73.N-GLY69.O 53.73
TYR65.OH-TYR677.OH 53.73
HID146.ND1-LYS153.O 53.73
GLN614.N-VAL610.O 53.73
ALA667.N-ASN593.OD1 54.73
TYR543.OH-HID245.O 55.22
ALA201.N-ILE197.O 56.22
VAL425.N-ASN246.OD1 56.22
ALA272.N-PRO268.O 56.72
TYR678.OH-ASN595.OD1 57.21
ILE426.N-ASN547.OD1 57.71
CYS354.N-ASN202.OD1 57.71
CYS655.N-SER644.O 57.71
LEU563.N-ALA289.O 58.21
ASN547.ND2-ASN424.O 58.21
LEU504.N-GLU692.O 58.21
VAL362.N-GLN358.O 58.21
VAL123.N-GLY93.O 58.71
LEU676.N-PHE672.O 59.20
TYR19.N-ALA15.O 59.70
VAL717.N-VAL710.O 60.20
TYR127.OH-GLN100.OE1 61.19
ASN306.N-CYS732.O 61.69
VAL363.N-LEU359.O 61.69
VAL366.N-VAL362.O 62.19
ARG640.N-TYR636.O 62.69
VAL314.N-TYR310.O 63.68
ALA313.N-PHE309.O 65.67
ASN595.N-THR591.O 65.67
ARG616.N-ASN612.O 65.67
LYS673.N-ILE669.O 66.17
CYS620.N-ARG616.O 66.67
ALA546.N-PHE542.O 66.67
PHE635.N-PHE631.O 67.16
TYR184.OH-ASN204.OD1 67.16
ASN204.OD1-TYR184.OH 67.16
CYS200.N-CYX196.O 70.15
LEU359.N-ASP355.O 70.15
Model peptideBdis-RdRp
LEU219.N-GLY235.O 52.74
HID146.ND1-LYS153.O 52.74
GLN614.N-VAL610.O 52.74
ASP415.N-TYR411.O 53.23
ARG87.N-CYS83.O 53.23
VAL244.N-TYR236.O 53.23
VAL750.N-ILE746.O 53.73
GLN588.N-PHE584.O 53.73
LEU639.N-PHE635.O 54.23
VAL717.N-VAL710.O 54.73
VAL654.N-MET505.O 55.22
LEU359.N-ASP355.O 55.22
ALA313.N-PHE309.O 55.72
ARG73.N-GLY69.O 55.72
MET558.N-THR430.O 56.22
CYS655.N-SER644.O 56.72
ALA592.N-GLN588.O 56.72
ALA546.N-PHE542.O 56.72
TYR767.OH-PRO722.O 57.21
ASN458.N-SER454.O 57.21
ASN306.N-CYS732.O 57.71
ALA201.N-ILE197.O 57.71
TYR65.OH-TYR677.OH 57.71
VAL590.N-ILE586.O 57.71
ALA667.N-ASN593.OD1 58.21
VAL314.N-TYR310.O 58.71
VAL366.N-VAL362.O 58.71
VAL362.N-GLN358.O 58.71
ARG640.N-TYR636.O 58.71
ILE522.N-ASN518.O 59.70
VAL363.N-LEU359.O 59.70
VAL147.N-PRO154.O 60.20
LYS673.N-ILE669.O 60.20
THR209.OG1-LEU206.O 61.19
CYS587.N-VAL583.O 62.69
CYS620.N-ARG616.O 63.18
TYR127.OH-GLN100.OE1 64.68
CYS200.N-CYX196.O 65.67
TYR19.N-ALA15.O 65.67
PHE635.N-PHE631.O 66.67
ARG616.N-ASN612.O 66.67
Model peptideCdis-RdRp
Table 3.15 The 20 μs MD-HBs (with occupancy rates ≥35%) within the RaRp (A-chain) of the peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models in [321]
190 3 RNA-Dependent RNA Polymerase (RdRp)
PHE238.N-GLY242.O 53.73
ASN547.ND2-ASN424.O 53.23
LYS566.N-GLU555.O 52.74
VAL244.N-TYR236.O 51.74
GLN614.N-VAL610.O 51.24
VAL717.N-VAL710.O 51.24
LEU728.N-PRO724.O 51.24
ALA592.N-GLN588.O 50.75
TYR65.OH-TYR677.OH 50.75
SER668.N-ASN671.OD1 50.25
GLN679.NE2-GLN588.OE1 49.75
SER554.N-CYS549.O 49.25
VAL243.N-ASN187.OD1 48.76
TYR128.N-VAL124.O 48.76
LEU466.N-HIE462.O 48.76
VAL232.N-ARG221.O 48.26
THR138.N-ILE134.O 47.76
LEU639.N-PHE635.O 47.76
THR38.OG1-GLU34.O 47.76
LEU76.N-VAL72.O 47.76
MET14.N-GLN100.O 47.26
LYS33.N-CYS29.O 47.26
ILE426.N-ASN547.OD1 47.26
TYR107.N-ASN99.O 47.26
SER599.OG-ASN595.O 46.77
ASN458.N-SER454.O 46.77
ILE35.N-THR31.O 46.77
ASN397.N-GLY393.O 46.77
LEU360.N-ILE356.O 46.27
ASP311.N-LYS307.O 46.27
THR38.N-GLU34.O 46.27
CYS559.N-SER562.O 46.27
CYS83.N-THR79.O 45.77
LEU198.N-ASP194.O 45.77
LYS435.N-ARG445.O 45.77
ASN612.N-LYS608.O 45.77
GLN712.N-ASP715.O 45.27
ALA550.N-ALA546.O 45.27
GLN614.NE2-LEU597.O 44.78
ILE469.N-LEU465.O 44.28
ASN518.ND2-GLU240.OE2 44.28
MET646.N-VAL653.O 44.28
LYS531.NZ-PHE370.O 44.28
SER658.N-ASN501.O 43.78
MET708.N-LEU719.O 52.74
LEU198.N-ASP194.O 51.74
ASN581.N-THR577.O 51.74
TYR678.OH-ASN595.OD1 51.24
ASN458.N-SER454.O 50.75
CYS83.N-THR79.O 50.75
LEU360.N-ILE356.O 50.25
VAL362.N-GLN358.O 50.25
CYS549.N-LEU545.O 50.25
GLN614.N-VAL610.O 49.75
ASN595.N-THR591.O 49.75
LEU219.N-GLY235.O 49.75
LYS493.N-HIE489.O 49.25
ILE469.N-LEU465.O 49.25
ALA580.N-THR576.O 48.76
ASN204.N-CYS200.O 48.76
VAL64.N-ASP60.O 48.76
MET86.N-PHE82.O 48.26
VAL557.N-TYR564.O 48.26
ARG22.N-VAL18.O 48.26
GLU692.N-LEU504.O 48.26
PHE207.N-PHE203.O 48.26
THR38.N-GLU34.O 47.76
ILE223.N-PHE230.O 47.76
ASP311.N-LYS307.O 47.76
MET14.N-GLN100.O 47.76
THR591.N-CYS587.O 47.26
VAL363.N-LEU359.O 47.26
MET523.N-MET519.O 47.26
GLN614.NE2-LEU597.O 46.77
ASN624.N-GLU619.O 46.77
TYR65.N-ILE61.O 46.77
ILE426.N-ASN547.OD1 46.77
TYR622.N-TYR618.O 46.27
HID772.N-ALA768.O 46.27
THR138.N-ILE134.O 45.77
THR209.OG1-LEU206.O 45.77
VAL243.N-ASN187.OD1 45.77
LEU492.N-TRP488.O 45.77
VAL123.N-GLY93.O 44.78
TYR636.N-VAL632.O 44.28
VAL244.N-TYR236.O 44.28
ILE35.N-THR31.O 44.28
LEU466.N-HIE462.O 44.28
ASP367.N-VAL363.O 44.78
HID237.N-GLY217.O 45.27
LEU76.N-VAL72.O 45.27
ARG541.N-SER537.O 45.27
GLN712.N-ASP715.O 45.27
VAL590.N-ILE586.O 45.77
VAL244.N-TYR236.O 45.77
CYS549.N-LEU545.O 45.77
LEU504.N-GLU692.O 45.77
VAL92.N-ILE113.O 45.77
ILE426.N-ASN547.OD1 45.77
ASN547.ND2-ASN424.O 45.77
ILE522.N-ASN518.O 45.77
ASP174.N-LEU170.O 46.27
ASN246.N-THR234.O 47.26
SER129.OG-ASP355.OD1 47.26
GLN679.N-VAL675.O 47.26
CYS83.N-THR79.O 47.26
TYR622.N-TYR618.O 47.26
ILE35.N-THR31.O 47.76
GLN358.N-ASP355.OD1 48.26
CYS655.N-SER644.O 48.26
VAL64.N-ASP60.O 48.76
TYR622.OH-ASP355.OD2 48.76
LEU360.N-ILE356.O 49.25
VAL557.N-TYR564.O 49.75
TYR678.OH-ASN595.OD1 50.25
TYR65.N-ILE61.O 50.25
LYS531.NZ-PHE370.O 50.25
LYS673.N-ILE669.O 50.25
GLN614.N-VAL610.O 50.25
THR38.OG1-GLU34.O 50.25
LEU130.N-SER126.O 50.75
VAL314.N-TYR310.O 50.75
PHE238.N-GLY242.O 50.75
HID772.N-ALA768.O 50.75
ILE223.N-PHE230.O 51.24
THR138.OG1-ILE134.O 51.24
MET14.N-GLN100.O 52.24
THR38.N-GLU34.O 52.24
LEU728.N-PRO724.O 52.74
TYR677.OH-TYR53.O 52.74
LEU198.N-ASP194.O 52.74
MET646.N-VAL653.O 53.23
LYS33.N-CYS29.O 44.78
ASN246.N-THR234.O 45.27
ASP174.N-LEU170.O 45.27
MET456.N-ILE452.O 45.77
GLU692.N-LEU504.O 46.27
LEU639.N-PHE635.O 46.27
LYS531.NZ-TYR373.O 46.77
CYS587.N-VAL583.O 46.77
ILE647.N-THR476.O 47.26
ARG169.N-PHE165.O 47.26
LYS531.NZ-PHE370.O 47.76
TYR678.OH-ASN595.OD1 47.76
LEU417.N-ASP413.O 47.76
ALA89.N-ALA85.O 47.76
TYR128.N-VAL124.O 48.26
ILE223.N-PHE230.O 48.26
HID237.N-GLY217.O 48.26
TYR622.OH-ASP355.OD2 48.76
VAL232.N-ARG221.O 48.76
VAL362.N-GLN358.O 48.76
VAL243.N-ASN187.OD1 48.76
ILE469.N-LEU465.O 48.76
VAL654.N-MET505.O 49.25
VAL557.N-TYR564.O 49.25
ASN458.N-SER454.O 49.25
ASN88.N-ASP84.O 49.25
GLN614.N-VAL610.O 49.25
LYS493.N-HIE489.O 49.75
TYR65.OH-TYR677.OH 49.75
ASN58.N-ASP54.O 49.75
ASP311.N-LYS307.O 49.75
ALA592.N-GLN588.O 49.75
LEU360.N-ILE356.O 49.75
LEU781.N-TYR777.O 50.25
VAL314.N-TYR310.O 50.25
PHE238.N-GLY242.O 50.25
MET523.N-MET519.O 50.75
TYR264.N-GLU260.O 51.24
LEU261.N-SER257.O 51.24
LEU466.N-HIE462.O 51.24
ILE522.N-ASN518.O 51.74
LEU36.N-LEU32.O 51.74
ASN595.N-THR591.O 51.74
THR38.N-GLU34.O 52.24
ILE647.N-THR476.O 45.27
VAL557.N-TYR564.O 45.77
VAL244.N-TYR236.O 45.77
VAL243.N-ASN187.OD1 45.77
PHE230.N-ILE223.O 46.27
LEU545.N-ARG541.O 46.27
MET646.N-VAL653.O 46.27
VAL288.N-LEU563.O 46.27
HID237.N-GLY217.O 46.27
ALA419.N-ASP415.O 46.77
ALA524.N-LEU520.O 46.77
VAL654.N-MET505.O 46.77
ASN246.N-THR234.O 47.26
LEU36.N-LEU32.O 47.26
MET523.N-MET519.O 47.76
VAL447.N-ASN433.O 47.76
TYR128.N-VAL124.O 47.76
THR138.N-ILE134.O 48.26
TYR638.OH-LEU665.O 48.76
ASP415.N-TYR411.O 48.76
ILE522.N-ASN518.O 48.76
ASP84.N-VAL80.O 48.76
THR591.OG1-CYS587.O 48.76
LEU360.N-ILE356.O 48.76
SER668.N-ASN671.OD1 49.25
ASP311.N-LYS307.O 49.25
CYS559.N-SER562.O 49.25
ASN612.N-LYS608.O 49.25
THR38.N-GLU34.O 49.75
THR38.OG1-GLU34.O 50.25
LEU198.N-ASP194.O 50.25
VAL750.N-ILE746.O 50.25
ILE778.N-TYR774.O 50.25
ALA592.N-GLN588.O 50.75
ASN58.N-ASP54.O 50.75
LYS33.N-CYS29.O 51.24
CYS549.N-LEU545.O 51.24
TYR677.OH-TYR53.O 51.24
THR591.N-CYS587.O 52.24
CYS83.N-THR79.O 52.24
MET86.N-PHE82.O 52.24
ILE223.N-PHE230.O 52.24
CYS587.N-VAL583.O 52.74
ASN397.N-GLY393.O 52.74
ASN204.N-CYS200.O 43.78
ASN612.N-LYS608.O 43.78
MET14.N-GLN100.O 44.28
ILE469.N-LEU465.O 44.28
GLN74.N-GLU70.O 44.28
GLN712.N-ASP715.O 44.28
ARG459.N-THR455.O 44.78
GLN776.N-HID772.O 44.78
VAL565.N-PHE286.O 45.27
HID772.N-ALA768.O 45.27
LEU76.N-VAL72.O 45.27
PHE230.N-ILE223.O 45.77
ILE426.N-ASN547.OD1 45.77
VAL583.N-TYR579.O 45.77
PHE542.N-LEU538.O 45.77
VAL64.N-ASP60.O 46.27
GLN679.N-VAL675.O 46.27
MET86.N-PHE82.O 46.27
LYS33.N-CYS29.O 46.77
LEU360.N-ILE356.O 46.77
THR138.OG1-ILE134.O 46.77
LEU781.N-TYR777.O 47.26
ILE35.N-THR31.O 47.26
MET456.N-ILE452.O 47.26
THR136.OG1-PRO351.O 47.76
ILE156.N-SER145.O 47.76
ASN581.N-THR577.O 47.76
LEU617.N-LEU613.O 47.76
LEU36.N-LEU32.O 48.26
ILE223.N-PHE230.O 48.26
CYS354.N-ASN202.OD1 48.26
ASN88.N-ASP84.O 48.76
LEU504.N-GLU692.O 48.76
TYR264.N-GLU260.O 49.75
VAL123.N-GLY93.O 49.75
CYS83.N-THR79.O 49.75
THR138.N-ILE134.O 50.25
ASN397.N-GLY393.O 50.75
TYR184.OH-ASN204.OD1 50.75
LEU598.N-VAL594.O 50.75
THR591.N-CYS587.O 51.74
THR38.N-GLU34.O 51.74
ASP174.N-LEU170.O 52.24
SER668.N-ASN671.OD1 52.24
Supplementary Information 191
TYR496.N-LEU492.O 43.28
ASP174.N-LEU170.O 43.78
ASN547.N-TYR543.O 43.28
VAL92.N-ILE113.O 43.78
ALA419.N-ASP415.O 43.78
THR138.N-ILE134.O 43.28
THR138.N-ILE134.O 42.29
GLN358.N-ASP355.OD1 41.79
PHE230.N-ILE223.O 41.79
ALA524.N-LEU520.O 42.29
HIE271.N-ASP267.O 40.80
ASN624.N-GLU619.O 40.80
GLU167.N-TYR163.O 40.30
LEU36.N-LEU32.O 37.31
ARG541.N-SER537.O 37.31
TYR564.N-VAL557.O 36.82
TYR264.N-GLU260.O 36.82
MET491.N-GLY487.O 39.30
TYR496.N-LEU492.O 39.30
ILE384.N-GLN463.OE1 39.30
TYR128.N-VAL124.O 38.81
CYS549.N-LEU545.O 37.31
VAL123.N-GLY93.O 37.31
ASP174.N-LEU170.O 39.80
HID237.N-GLY217.O 39.80
LEU598.N-VAL594.O 37.81
ARG22.NH2-ASP355.OD2 37.31
THR494.OG1-ASN490.O 39.80
ASN246.N-THR234.O 39.80
THR591.N-CYS587.O 38.31
ALA89.N-ALA85.O 37.81
ILE452.N-ALA392.O 40.30
TYR369.N-VAL365.O 40.30
SER599.OG-ASN595.O 38.81
ASN612.N-LYS608.O 38.81
ILE384.N-ALA380.O 39.30
ARG239.NE-GLU240.OE1 39.30
ALA578.N-ASP574.O 39.30
ASN204.ND2-GLU240.O 39.30
CYS559.N-SER562.O 39.30
ASN624.N-GLU619.O 39.30
TYR107.N-ASN99.O 39.80
LEU617.N-LEU613.O 41.29
MET646.N-VAL653.O 39.30
TYR636.N-VAL632.O 39.30
LEU613.N-TYR609.O 39.30
ARG459.N-THR455.O 39.80
ASP367.N-VAL363.O 39.80
LYS566.N-GLU555.O 40.30
ASN612.N-LYS608.O 40.30
GLY449.N-GLN431.O 40.30
ASP248.N-ASN424.OD1 40.30
THR352.OG1-ASN681.OD1 41.29 THR472.OG1-SER468.O 40.80
LEU219.N-GLY235.O 40.30 TYR65.OH-TYR677.OH 40.30 TYR46.OH-ASN58.OD1 40.30
VAL552.N-GLU548.O 38.81
TYR767.OH-PRO722.O 38.81
GLU692.N-LEU504.O 38.31
LEU613.N-TYR609.O 40.30
ASN518.ND2-GLU240.OE2 41.29
LEU504.N-GLU692.O 41.29
SER662.N-SER658.O 41.29
VAL92.N-ILE113.O 41.29
ILE452.N-ALA392.O 41.79
VAL123.N-GLY93.O 41.79
VAL583.N-TYR579.O 40.30
VAL552.N-GLU548.O 40.30
LEU613.N-TYR609.O 40.30
LEU598.N-VAL594.O 40.30
LYS33.N-CYS29.O 41.29
LEU130.N-SER126.O 40.30
VAL557.N-TYR564.O 38.81
TYR236.N-VAL244.O 38.81
PHE238.N-GLY242.O 40.30
ILE754.N-VAL750.O 40.30
LEU528.N-ALA524.O 39.30
LEU95.N-VAL123.O 38.81
PHE230.N-ILE223.O 40.80
ASN547.ND2-ASN424.O 41.79
ALA419.N-ASP415.O 41.29 LEU617.N-LEU613.O 40.80
ALA75.N-ARG71.O 39.30
VAL583.N-TYR579.O 39.30
ASN88.N-ASP84.O 40.80
SER658.N-ASN501.O 40.80
TYR564.N-VAL557.O 40.80
THR13.N-ASP16.OD2 41.79
LYS171.N-GLU167.O 41.29
LYS78.NZ-ASN103.O 39.80
CYS587.N-VAL583.O 39.30
LEU261.N-SER257.O 41.29
LEU728.N-PRO724.O 41.79
ILE586.N-SER582.O 41.29
SER668.N-ASN671.OD1 41.29
LEU261.N-SER257.O 39.80
ILE778.N-TYR774.O 39.80
ASN58.N-ASP54.O 41.29
GLN551.NE2-ILE426.O 41.29
LEU719.N-MET708.O 42.29 TYR564.N-VAL557.O 42.29
TYR636.N-VAL632.O 41.79 SER208.N-ASN204.O 41.79 THR760.OG1-TYR757.O 41.79
ASP367.N-VAL363.O 40.30
LEU613.N-TYR609.O 40.30
THR421.N-LEU417.O 39.80
TYR718.N-HIE489.ND1 41.29
THR115.N-GLY90.O 42.29
VAL710.N-VAL717.O 42.79
TYR65.N-ILE61.O 42.79
VAL64.N-ASP60.O 43.78
PHE584.N-ALA580.O 41.29
ALA89.N-ALA85.O 41.79
LYS78.NZ-ASN103.O 42.29
ASN397.N-GLY393.O 42.29
CYS587.N-VAL583.O 42.79
ALA524.N-LEU520.O 41.29
ASN246.N-THR234.O 40.80
LEU492.N-TRP488.O 40.80
LEU617.N-LEU613.O 41.79
CYS559.N-SER562.O 41.79
TYR636.N-VAL632.O 41.29
ASP248.N-ASN424.OD1 40.80
LEU36.N-LEU32.O 41.79
ASN204.ND2-GLU240.O 43.28 MET14.N-GLN100.O 43.28
TYR128.N-VAL124.O 42.79 ILE778.N-TYR774.O 42.79
SER582.OG-ALA578.O 41.29
LEU219.N-GLY235.O 41.29
ASN612.N-LYS608.O 42.29
LYS78.NZ-ASN103.O 42.29
LYS566.N-GLU555.O 41.79
LYS435.N-ARG445.O 43.28
ILE754.N-VAL750.O 42.79
ASN88.N-ASP84.O 42.29
LEU617.N-LEU613.O 41.79
GLU548.N-ARG544.O 42.79
TYR264.N-GLU260.O 42.79
PHE230.N-ILE223.O 43.78
ASN204.N-CYS200.O 43.78
LYS566.N-GLU555.O 43.28 ARG544.N-HIE540.O 43.28 LEU466.N-HIE462.O 43.28
THR591.OG1-CYS587.O 43.28
GLN588.NE2-ASN680.OD1 43.28
VAL447.N-ASN433.O 42.79
ILE778.N-TYR774.O 43.28
THR38.OG1-GLU34.O 43.78
ASN585.N-ASN581.O 44.28 VAL18.N-MET14.O 44.28
ARG221.N-VAL232.O 43.28
THR760.OG1-TYR757.O 43.28
TYR721.N-HID706.O 43.78
THR591.N-CYS587.O 44.28 LEU130.N-SER126.O 44.28
ILE469.N-LEU465.O 44.28 LEU639.N-PHE635.O 43.28
ASN681.ND2-ALA515.O 43.78
MET708.N-LEU719.O 43.78
ALA89.N-ALA85.O 43.78
LYS398.N-PRO395.O 43.78
Model peptideAdis-RdRp TYR107.N-ASN99.O 44.78
MET558.N-THR430.O 44.78
Model peptideB-RdRp
LYS171.N-GLU167.O 43.78
Model peptideA-RdRp
THR115.N-GLY90.O 43.78
Model peptideC-RdRp
LEU492.N-TRP488.O 39.30
VAL18.N-MET14.O 39.30
TYR496.N-LEU492.O 39.80
ALA265.N-LEU261.O 39.80
VAL232.N-ARG221.O 39.80
GLY217.N-HID237.O 39.80
THR472.OG1-SER468.O 39.80
LYS531.NZ-TYR373.O 39.80
VAL565.N-PHE286.O 40.30
LEU728.N-PRO724.O 40.30
LEU261.N-SER257.O 40.30
LEU262.N-PHE258.O 40.30
ASN204.N-CYS200.O 40.80
ARG87.N-CYS83.O 40.80
GLN614.NE2-LEU597.O 40.80
ARG459.N-THR455.O 41.29
TYR622.N-TYR618.O 41.29
TYR622.OH-ASP355.OD2 41.79
ILE156.N-SER145.O 41.79
ALA550.N-ALA546.O 41.79
MET708.N-LEU719.O 41.79
GLN712.N-ASP715.O 42.29
ILE469.N-LEU465.O 42.29
THR138.OG1-ILE134.O 42.29
ILE35.N-THR31.O 42.79
LEU76.N-VAL72.O 42.79
TYR176.OH-GLU144.OE1 43.28
GLU692.N-LEU504.O 43.28
ASP174.N-LEU170.O 43.28
ASP248.N-ASN424.OD1 43.78
MET14.N-GLN100.O 43.78
GLN74.N-GLU70.O 43.78
ASP367.N-VAL363.O 44.28
LEU553.N-CYS549.O 44.78
LYS493.N-HIE489.O 44.78
VAL147.N-PRO154.O 44.78
ARG169.N-PHE165.O 44.78
LEU291.N-GLY561.O 44.78
LYS435.N-ARG445.O 44.78
TYR543.N-SER539.O 45.27
LEU617.N-LEU613.O 45.27
TYR564.N-VAL557.O 45.27
Model peptideBdis-RdRp
LEU492.N-TRP488.O 38.81
LYS493.N-HIE489.O 38.81
ASN624.N-GLU619.O 38.81
VAL594.N-VAL590.O 38.81
THR760.OG 1-TYR757.O 39.30
VAL18.N-MET14.O 39.30
SER129.OG-ASP355.OD1 39.30
LEU291.N-GLY561.O 39.80
VAL232.N-ARG221.O 39.80
ARG221.N-VAL232.O 39.80
ARG530.N-LEU526.O 39.80
LYS467.N-GLN463.O 40.30
ASN547.N-TYR543.O 40.80
TYR65.N-ILE61.O 40.80
MET646.N-VAL653.O 40.80
ASN595.N-THR591.O 40.80
CYS559.N-SER562.O 40.80
SER658.N-ASN501.O 40.80
TYR176.OH-GLU144.OE2 40.80
LYS566.N-GLU555.O 41.29
TYR564.N-VAL557.O 41.29
TYR622.OH-ASP355.OD2 41.79
HID237.N-GLY217.O 41.79
PHE584.N-ALA580.O 41.79
THR38.OG1-GLU34.O 42.29
ASN585.N-ASN581.O 42.29
ALA89.N-ALA85.O 42.29
VAL288.N-LEU563.O 42.29
LYS171.N-GLU167.O 42.29
PHE207.N-PHE203.O 42.29
THR591.OG1-CYS587.O 42.29
SER599.OG-ASN595.O 42.79
LEU728.N-PRO724.O 42.79
ASP311.N-LYS307.O 42.79
TYR636.N-VAL632.O 42.79
ASN58.N-ASP54.O 42.79
LYS435.N-ARG445.O 42.79
TYR496.N-LEU492.O 43.28
TYR677.OH-TYR53.O 43.28
LEU261.N-SER257.O 43.28
ASP84.N-VAL80.O 43.28
THR430.N-MET556.O 43.78
Model peptideCdis-RdRp
Table 3.16 The 20 μs MD-HBs (with occupancy rates ≥35%) within the RaRp (A-chain) of the peptideA-RdRp, peptideB-RdRp, peptideC-RdRp, peptideAdis-RdRp, peptideBdis-RdRp, and peptideCdis-RdRp models in [321] (continuation)
192 3 RNA-Dependent RNA Polymerase (RdRp)
ALA419.N-ASP415.O 36.82
VAL653.N-MET646.O 36.32
ASN657.ND2-HIE642.ND1 36.32
VAL594.N-VAL590.O 36.32
ASN58.N-ASP54.O 36.32
VAL18.N-MET14.O 36.32
THR760.OG1-TYR757.O 36.32
ASP415.N-TYR411.O 35.82
TYR622.N-TYR618.O 35.82
PHE207.N-PHE203.O 35.82
VAL675.N-ASN671.O 35.82
ASN624.N-GLU619.O 35.32
ARG459.N-THR455.O 35.32
GLU747.N-THR743.O 35.32
ARG87.N-CYS83.O 34.83
ALA580.N-THR576.O 34.83
GLU548.N-ARG544.O 34.83
TYR622.OH-ASP355.OD2 34.83
ARG169.N-PHE165.O 34.83
ARG221.N-VAL232.O 34.83
LEU130.N-SER126.O 34.33
SER525.N-ARG521.O 34.33
ASN204.ND2-GLU240.O 33.83
ASN204.ND2-PRO186.O 33.33
VAL710.N-VAL717.O 33.33
PHE542.N-LEU538.O 33.33
ILE727.N-ASP723.O 33.33
HID772.N-ALA768.O 33.33
THR13.N-ASP16.OD1 33.33
ARG530.NH2-GLU364.OE2 32.84
TYR420.N-ALA416.O 32.84
LEU719.N-MET708.O 32.84
GLN100.NE2-GLY104.O 32.84
GLN776.N-HID772.O 32.84
HIE271.N-ASP267.O 32.84
LEU77.N-ARG73.O 32.84
ARG611.N-ASP607.O 32.84
ASN349.ND2-MET516.O 32.84
VAL225.N-VAL228.O 32.34
TYR310.N-ASN306.O 32.34
ALA637.N-ASN633.O 32.34
ASN349.ND2-ARG514.O 32.34
ALA661.N-ASN657.O 32.34
ILE522.N-ASN518.O 31.84
SER662.N-SER658.O 38.81
LYS33.N-CYS29.O 38.81
GLN712.N-ASP715.O 38.81
GLN776.N-HID772.O 38.81
ARG459.N-THR455.O 38.81
VAL232.N-ARG221.O 38.81
VAL18.N-MET14.O 38.31
VAL552.N-GLU548.O 37.81
ARG22.NH2-ASP355.OD2 37.81
LEU95.N-VAL123.O 37.31
CYX377.N-THR534.O 36.82
GLY217.N-HID237.O 36.82
GLU701.N-GLU692.OE1 36.82
ARG87.N-CYS83.O 36.32
LYS171.N-GLU167.O 36.32
ASN547.ND2-ASN424.O 36.32
THR352.OG1-ASN681.OD1 36.32
VAL654.N-MET505.O 36.32
LEU719.N-MET708.O 36.32
ILE522.N-ASN518.O 35.82
VAL225.N-VAL228.O 35.82
LEU639.N-PHE635.O 35.82
ARG521.N-PRO517.O 35.82
HIE462.N-ASN458.O 35.82
LEU598.N-VAL594.O 35.32
LEU170.N-THR166.O 35.32
THR13.N-ASP16.OD1 35.32
TYR107.N-ASN99.O 34.83
TRP690.N-GLY506.O 34.83
LEU528.N-ALA524.O 34.83
ASN204.ND2-GLU240.O 34.83
ALA753.N-PHE749.O 34.83
ASN547.N-TYR543.O 34.33
ALA20.N-ASP16.O 33.83
HID237.ND1-SER215.O 33.83
THR707.N-PRO699.O 33.83
TRP180.NE1-HID199.NE2 33.33
HID532.ND1-LEU528.O 33.33
THR430.N-MET556.O 33.33
TYR46.OH-ASN58.OD1 33.33
VAL770.N-GLU766.O 33.33
GLY400.N-PHE396.O 33.33
VAL594.N-VAL590.O 32.84
ARG611.N-ASP607.O 32.84
ARG530.NH1-GLU364.OE2 33.33
MET456.N-ILE452.O 33.33
ALA470.N-LEU466.O 33.33
ARG611.N-ASP607.O 33.83
PHE211.N-PHE207.O 34.33
TYR564.N-VAL557.O 34.33
MET708.N-LEU719.O 34.33
GLN614.NE2-LEU597.O 34.33
PHE286.N-PHE216.O 34.83
TYR310.N-ASN306.O 34.83
ASP248.N-ASN424.OD1 34.83
TYR509.OH-ASN585.OD1 35.32
LYS78.NZ-ASN105.OD1 35.32
VAL527.N-MET523.O 35.32
PHE418.N-GLN414.O 35.32
ARG530.NE-ASP194.OD2 35.32
SER662.N-SER658.O 35.32
TYR264.N-GLU260.O 35.32
THR352.OG1-ASN681.OD1 35.32
GLN100.NE2-GLY104.O 35.82
VAL18.N-MET14.O 35.82
VAL232.N-ARG221.O 35.82
VAL123.N-GLY93.O 35.82
LEU563.N-VAL288.O 36.32
ALA637.N-ASN633.O 36.32
THR421.N-LEU417.O 36.32
THR457.OG1-CYS453.O 36.32
GLN776.N-HID772.O 36.82
VAL478.N-ILE647.O 37.31
THR472.OG1-SER468.O 37.31
PHE207.N-PHE203.O 37.31
VAL243.N-ASN187.OD1 37.31
LEU170.N-THR166.O 37.81
SER658.N-ASN501.O 37.81
ASN88.N-ASP84.O 37.81
TYR638.OH-LEU665.O 38.31
LEU775.N-PHE771.O 38.31
VAL710.N-VAL717.O 38.31
GLU747.N-THR743.O 38.31
ALA550.N-ALA546.O 38.31
GLU692.N-LEU504.O 38.31
THR115.N-GLY90.O 38.81
THR430.N-MET556.O 38.81
ARG22.N-VAL18.O 38.81
ALA753.N-PHE749.O 33.83
ILE586.N-SER582.O 33.83
ASP84.N-VAL80.O 33.83
ARG544.N-HIE540.O 33.83
LYS171.N-GLU167.O 33.83
ALA589.N-ASN585.O 34.33
ILE727.N-ASP723.O 34.33
ASN657.N-HIE642.O 34.83
TYR718.OH-LEU695.O 34.83
LYS78.N-GLN74.O 34.83
TYR622.N-TYR618.O 34.83
VAL632.N-ASP628.O 34.83
PHE173.N-ARG169.O 35.32
TYR236.N-VAL244.O 35.32
TYR774.OH-ILE727.O 35.32
THR494.OG1-ASN490.O 35.82
ARG530.NE-ASP194.OD2 35.82
GLN414.N-SER410.O 35.82
TYR420.N-ALA416.O 35.82
LYS78.NZ-ASN103.O 35.82
HID237.ND1-SER215.O 35.82
THR421.OG1-LEU417.O 36.32
TYR718.N-HIE489.ND1 36.32
ILE384.N-GLN463.OE1 36.32
ALA419.N-ASP415.O 36.32
GLU747.N-THR743.O 36.32
ASP415.N-TYR411.O 36.32
VAL244.N-TYR236.O 36.32
ARG541.N-SER537.O 36.82
THR760.OG1-TYR757.O 36.82
TYR721.N-HID706.O 36.82
ARG611.N-ASP607.O 36.82
THR209.OG1-LEU206.O 36.82
ARG87.N-CYS83.O 37.31
GLN712.N-ASP715.O 37.81
SER525.N-ARG521.O 37.81
SER582.OG-ALA578.O 37.81
LEU775.N-PHE771.O 38.31
THR421.N-LEU417.O 38.31
PHE207.N-PHE203.O 38.81
TYR46.OH-ASN58.OD1 39.30
ILE35.N-THR31.O 39.30
CYS559.N-SER562.O 39.30
VAL447.N-ASN433.O 39.30
LEU130.N-SER126.O 35.32
ILE429.N-ALA266.O 35.32
ASN204.ND2-PRO186.O 35.32
LYS566.N-GLU555.O 35.32
ASN458.N-SER454.O 35.32
TYR721.N-HID706.O 35.32
SER658.N-ASN501.O 35.32
TYR39.OH-ASN103.OD1 35.82
THR136.OG1-PRO351.O 35.82
ARG611.N-ASP607.O 35.82
VAL710.N-VAL717.O 36.32
HIE271.NE2-ALA265.O 36.32
TYR636.N-VAL632.O 36.32
ARG221.N-VAL232.O 36.32
LEU598.N-VAL594.O 36.82
ALA380.N-ASP415.OD2 36.82
MET456.N-ILE452.O 36.82
ARG73.NE-GLU70.OE2 37.31
GLN776.N-HID772.O 37.31
HIE462.N-ASN458.O 37.31
LEU613.N-TYR609.O 37.31
PHE238.N-GLY242.O 37.31
TYR65.N-ILE61.O 37.31
PHE173.N-ARG169.O 37.31
LEU466.N-HIE462.O 37.81
VAL64.N-ASP60.O 37.81
TYR236.N-VAL244.O 37.81
ASN518.ND2-GLU240.OE2 37.81
ILE586.N-SER582.O 37.81
TYR420.N-ALA416.O 38.31
LEU639.N-PHE635.O 38.31
ASN88.N-ASP84.O 38.31
ILE91.N-MET86.O 38.31
MET432.N-MET558.O 38.81
TYR107.N-ASN99.O 38.81
ILE384.N-GLN463.OE1 38.81
LEU95.N-VAL123.O 38.81
HID237.ND1-SER215.O 38.81
LYS171.N-GLU167.O 38.81
TYR46.OH-ASN58.OD1 39.30
LEU775.N-PHE771.O 39.30
LEU219.N-GLY235.O 39.30
ASN624.N-GLU619.O 39.30
ILE727.N-ASP723.O 39.30
PHE177.N-PHE173.O 32.84
ALA637.N-ASN633.O 32.84
ARG73.NH2-GLU70.OE1 33.33
TYR46.OH-ASN58.OD1 33.33
GLN460.NE2-ILE378.O 33.33
THR421.N-LEU417.O 33.33
MET708.N-LEU719.O 33.33
VAL557.N-TYR564.O 33.83
TYR176.OH-GLU144.OE1 33.83
LEU613.N-TYR609.O 33.83
HIE462.N-ASN458.O 33.83
LEU676.N-PHE672.O 34.33
ARG541.N-SER537.O 34.33
ARG611.N-ASP607.O 34.33
VAL632.N-ASP628.O 34.33
THR115.N-GLY90.O 34.33
GLU692.N-LEU504.O 34.33
GLN551.NE2-ILE426.O 34.83
HIE271.N-ASP267.O 34.83
VAL243.N-ASN187.OD1 34.83
VAL675.N-ASN671.O 35.32
ASN458.ND2-GLN551.OE1 35.32
TYR420.N-ALA416.O 35.32
GLN100.NE2-GLY104.O 35.32
GLN614.NE2-LEU597.O 35.32
THR352.OG1-ASN681.OD1 35.82
ASN595.ND2-THR591.O 35.82
ARG169.N-PHE165.O 35.82
ILE754.N-VAL750.O 36.32
TYR128.N-VAL124.O 36.32
MET523.N-MET519.O 36.32
SER208.N-ASN204.O 36.32
VAL225.N-VAL228.O 36.82
LEU198.N-ASP194.O 36.82
ILE778.N-TYR774.O 36.82
ALA524.N-LEU520.O 36.82
VAL92.N-ILE113.O 36.82
ARG73.NE-GLU70.OE2 37.31
ASP367.N-VAL363.O 37.81
GLU747.N-THR743.O 37.81
TYR622.N-TYR618.O 37.81
ALA272.N-PRO268.O 38.31
ALA580.N-THR576.O 38.31
LEU95.N-VAL123.O 38.31
Supplementary Information 193
Chapter 4
RNA Helicase
Abstract Helicase and polymerase are coupling in the SARS-CoV-2 replicationtranscription complex (RTC). RNA helicase (NSP13) is a SARS-CoV-2 antiviral target too. It facilitates/stimulates SARS-CoV-2 RdRp backtracking. Molecular dynamics (MD) simulations of the NSP13.2 -BTC.−1U +1C and NSP13.2 BTC.−1U +1U complexes were done in Malone et al. (Proc Natl Acad Sci USA 118(19):e2102516118, 2021) and confirmed the results: “the single-stranded 3’segment of the product-RNA generated by backtracking extrudes through the RdRp NTP-entry tunnel, that a mismatched nucleotide at the product-RNA 3’end frays and enters the NTP-entry tunnel to initiate backtracking” but without detailed structural bioinformatics such as hydrogen bonds (HBs), salt bridges (SBs), .π -interactions (PIs), and hydrophobic interactions (HYDs) of the SARS-CoV-2NSP13 RNA helicase. This chapter presents some detailed structural bioinformatics such as HBs, SBs, PIs, and HYDs of the SARS-CoV-2-NSP13 RNA helicase in its optimized structure and then during its MD simulations. Keywords COVID-19 virus · RNA helicase (NSP13) · Binding with holo-RdRp and RNA · Optimization and MD (molecular dynamics) studies · Basic structural bioinformatics
4.1 Introduction The COVID-19 virus’ RNA-dependent RNA polymerase (RdRp, also named NSP12) is the central component of coronaviral replication/transcription machinery and appears to be a primary drug target for antivirals such as remdesivir [118, 225]. Structures of SARS-CoV-2 RdRp (RNA-dependent RNA polymerase) bound to the essential RNA helicase (NSP13) and RNA suggested the helicase facilitates/stimulates SARS-CoV-2 RdRp backtracking; backtracking is the reverse/backward motion of the RdRp on the template RNA, and backtracking may aid proofreading, viral transcription, and replication [64, 225]. The RdRp holoenzyme (holo-RdRp: NSP7/NSP8.2 /NSP12) is thought to coordinate with many © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_4
195
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cofactors (such as the NSP13 helicase and the NSP10/NSP14 proofreading assembly) to carry out its function. These cofactors are also essential for viral replication and are antiviral targets. Molecular dynamics (MD) simulations of the NSP13.2 -BTC.−1U +1C and NSP13.2 -BTC.−1U +1U complexes were done in [225], to confirm the results: “the single-stranded 3’-segment of the product-RNA generated by backtracking extrudes through the RdRp NTP-entry tunnel, that a mismatched nucleotide at the productRNA 3’-end frays and enters the NTP-entry tunnel to initiate backtracking.” This chapter presents detailed structural bioinformatics such as hydrogen bonds (HBs), salt bridges (SBs), .π -interactions (PIs), and hydrophobic interactions (HYDs) of the SARS-CoV-2-NSP13 RNA helicase in its optimized structure and its MD simulations.
4.2 Materials and Methods Six 5 .μs MD simulation trajectories (numbered 12366060, 12366092, 12366129, 12376232, 12376233, and 12376234) are presented in open databases [321]; in this chapter, we denote them as replicate 1 (rep1), replicate 2 (rep2), replicate 3 (rep3), replicate 4 (rep4), replicate 5 (rep5), replicate 6 (rep6), respectively, of the NSP13-bound SARS-CoV-2 replication-transcription complex (RTC) which are starting from a backtracked state [225] by the use of 7KRO.pdb (cryo-EM structure of NSP13.2 -BTC.5 ). Three replicates of trajectories [numbered 12366060, 12366092, and 12366129] are featuring p-RNA with a matched .−1U and a mismatched +1C, and another three replicates of trajectories [numbered 12376232, 12376233, and 12376234] are featuring p-RNA with a matched -1U, and +1C/U. A-, B-, C-, D-, E-, F-, P-, and T-chains of 7KRO.pdb are NSP12, NSP8a, NSP7, NSP8b, NSP13.1, NSP13.2, p-RNA, and t-RNA, respectively with ions Zn.2+ , Mg.2+ , and ADPs. We optimized the structures of NSP13, i.e., the EF-chains of 7KRO.pdb, and got some basic structural bioinformatics (such as HBs, SBs, PIs, and HYDs) about NSP13 helicase and then confirmed these basic bioinformatics during 5 .μs’ long MD simulations.
4.3 New Results and Discussions The optimized-12366060-EFchains model has 152 HBs, 48 SBs (within Echain: GLU142-ARG409, ASP204-LYS524, ASP223-ARG186, GLU136-ARG21, GLU162-LYS524, GLU551-LYS477, GLU201-ARG178, GLU353-LYS347, ASP32-LYS28, GLU420-ARG427, ASP328-LYS347, ASP534-ARG560, ASP344LYS345, ASP450-LYS460, GLU540-LYS320, GLU197-ARG337, GLU128LYS131, GLU261-ARG442, GLU201-ARG212, ASP315-ARG332, ASP583ARG579, GLU319-LYS569; within F-chain: GLU142-ARG409, ASP204-LYS524, ASP223-ARG186, GLU136-ARG21, GLU162-LYS524, GLU551-LYS477, GLU201-ARG178, GLU353-LYS347, ASP32-LYS28, GLU420-ARG427,
4.3 New Results and Discussions
197
ASP328-LYS347, ASP534-ARG560, ASP344-LYS345, GLU498-ARG502, ASP466-LYS467, GLU420-LYS430, ASP374-LYS288, ASP315-LYS345, GLU375-LYS288, ASP101-LYS28, GLU244-LYS276, GLU143-LYS146, GLU540-ARG443, GLU418-LYS430, ASP369-LYS394; between E-chain and F-chain: E:ASP160-F:ARG248), 9 .π -cations (F:LYS76.NZ-F:TYR64, E:LYS473.NZ-E:TYR582, F:LYS473.NZ-F:TYR582, E:LYS192.NZ-E:TYR185, F:LYS192.NZ-F:TYR185, F:ARG15.NH2-F:PHE24, E:LYS139.NZ-E:TYR182, E:LYS276.NZ-E:HID395, E:ARG332.NH2-E:HID311), and 21 .π -.π stackings (F:TYR70-F:TYR48, F:PHE81-F:PHE90, F:HID39-F:HID33-F:PHE106, F:HID395-F:TYR246, F:TYR299-F:TYR298, F:TYR114-F:TYR120, F:PHE200F:TYR198-F:PHE182, F:TYR198-F:PHE225, F:PHE262-F:TYR324, F:PHE499F:TRP506, E:PHE225-E:PHE200, E:TYR149-E:PHE145, E:TRP114-E:TYR120, E:TYR299-E:TYR298, E:TYR269-E:PHE291, E:PHE262-E:TYR324, E:PHE499E:TRP506-E:TYR543-E:TRP506). The optimized-12376232-EFchains model has 164 HBs, 49 SBs (within E-chain: GLU447-LYS462, GLU353-LYS347, GLU540-LYS320, GLU197ARG337, GLU197-ARG339, GLU201-LYS524, ASP223-ARG186, ASP534ARG560, ASP583-ARG579, ASP32-LYS28, GLU128-LYS131, GLU498ARG502, GLU201-ARG212, GLU142-LYS139, GLU143-LYS146, ASP369LYS394, ASP328-LYS347, ASP466-LYS465, ASP435-LYS271, GLU168LYS171, ASP483-LYS202, ASP204-ARG490, ASP315-ARG332, ASP542LYS569; within F-chain: GLU447-LYS465, GLU447-LYS467, GLU353-LYS347, GLU197-ARG337, GLU201-ARG178, ASP223-ARG186, ASP534-ARG560, ASP583-LYS460, ASP32-LYS28, GLU128-LYS131, GLU143-LYS146, ASP369LYS394, ASP328-LYS347, GLU168-LYS171, ASP315-ARG332, GLU418LYS430, GLU142-ARG409, GLU341-ARG212, ASP101-LYS28, GLU420LYS430, GLU162-ARG161, GLU551-LYS477, GLU136-ARG21, GLU244LYS276; between E-chain and F-chain: E:GLU341-F:ARG248), 13 .π -cations (F:HID245-E:LYS218.NZ+, F:LYS76.NZ+-F:TYR64, E:LYS76.NZ+-E:TYR64, E:LYS473.NZ+-E:TYR582, F:LYS473.NZ+-F:TYR582, E:LYS192.NZ+-E:TYR 185, F:ARG15.NH2+-F:PHE24, F:LYS139.NZ+-F:TYR382, E:LYS276.NZ+E:HID395, E:ARG332.NH2+-E:HID311, E:TYR211-E:ARG161.NH2+, E:TYR 205-E:ARG490.NH2+, E:TYR93-E:ALA1.N+), and 22 .π -.π stackings (F:TYR149F:PHE145, F:TRP167-F:TRP167, F:TYR198-F:PHE225-F:PHE200, F:PHE499F:TRP506-F:PHE499, F:PHE546-F:PHE561, F:TYR120-F:TRP114, F:HID290F:ADP1003, F:TYR324-F:PHE262, F:PHE106-F:PHE133, F:TYR298-F:TYR299, F:HID33-F:HID39, F:TYR48-F:TYR70, F:PHE81-F:PHE90, E:PHE200-E:PHE 225, E:TYR180-E:TYR149, E:PHE499-E:TRP506-E:TYR543-E:TRP506, E:TYR 298-E:TYR299, E:PHE106-E:PHE133). The RMSD value between the optimized-12366060-EFchains model and the optimized-12376232-EFchains model is 5.77368 Å. The ADP1003 ligand interaction diagrams with the E-chain and F-chain for each optimized model are shown in Fig. 4.1, where EF-chains’ residues 285, 286, 287, 289, 290, 320, 442, and 443 and Mg.2+ 1004 are always binding ADP1003. Seeing Fig. 4.2, we may know that the NSP13.1 residues ASP101-ASN102 are always exposed to the surface with negative charges; the two Ramachandran plots are also slightly different to each other.
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Fig. 4.1 RNA helicases NSP13.1 and NSP13.2 binding with the ADP. The first two graphs from left to right are for the optimized-12366060-EFchains model, and the last two graphs from left to right are for the optimized-12376232-EFchains model
Fig. 4.2 The Poisson-Boltzmann electrostatic surfaces and the Ramachandran plots for the optimized-12366060-EFchains model and the optimized-12376232-EFchains model respectively
The hydrophobic-hydrophilic surfaces for the optimized-12366060-EFchains model and the optimized-12376232-EFchains model of NSP13 helicase are shown in Fig. 4.3.
Fig. 4.3 The hydrophobic-hydrophilic surfaces for the optimized-12366060-EFchains model (left) and the optimized-12376232-EFchains model (right)
Tables 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9 and 4.10 list the SBs linking Echain NSP13.1 with ABCDFchains NSP12-NSP8a-NSP7-NSP8b-NSP13.2, the SBs linking Fchain NSP13.2 with ABCDEchains NSP12-NSP8a-NSP7-NSP8b-
With A-chain NSP12
A:ASP901-E:LYS94
A:ASP901-E:LYS94
A:ASP901-E:LYS94
A:ASP901-E:LYS94
A:ASP901-E:LYS94
A:ASP901-E:LYS94
.\E:
Rep1
Rep2
Rep3
Rep4
Rep5
Rep6
E:GLU341-B:LYS97
E:ASP328/GLU353-B:LYS165
F:GLU244-E:ARG186/LYS189/LYS218
C:ASP67/GLU74-E:ARG248
C:ASP67/GLU74-E:ARG248
E:ASP160-F:ARG248/LYS271 E:ASP344/GLU341-F:ARG248
D:ASP78/GLU77-E:ARG392 E:GLU244-D:LYS82
E:ASP344/GLU341-F:ARG248 F:ASP435-E:LYS218
E:ASP160-F:ARG248 E:GLU244-D:LYS82
F:ASP435-E:LYS218
D:GLU171-E:ARG248
F:ASP101/ASP105/GLU128-E:LYS189
E:GLU341-F:ARG248
D:GLU77-E:ARG392
D:GLU77-E:ARG392
E:ASP160-F:ARG248/LYS271
E:ASP260-D:LYS165
D:ASP52/GLU48-E:LYS76
F:ASP101/ASP105/GLU128-E:LYS189
D:ASP175-E:LYS271
F:ASP435-E:ARG161/LYS218
F:ASP101/ASP105/GLU128-E:LYS189
D:ASP52/GLU48-E:LYS76
F:GLU365-E:LYS189
F:GLU128/GLU244-E:LYS189
E:GLU244-C:LYS70 C:ASP67/GLU73/GLU74-E:ARG248
F:ASP328/GLU244/GLU353-E:LYS218
E:ASP160/GLU156-F:ARG248
E:GLU156-F:ARG248
F:ASP369-E:LYS218
E:ARG392-C:GLU23
D:ASP134-E:ARG248
E:GLU365-C:ARG21,
C:ASP67-E:ARG392/LYS276/LYS394
F:GLU128/GLU365-E:LYS189
E:GLU244-C:LYS70
F:GLU244-E:LYS189/LYS218
E:ASP160-F:ARG248/ARG392/LYS394
C:ASP67-E:ARG392/LYS276/LYS394 E:GLU365-C:ARG21
F:ASP101-E:LYS189
E:GLU341-F:ARG248
E:ASP328/GLU353-B:LYS165
D:ASP134-E:ARG248
F:GLU128-E:LYS189 F:GLU244-E:ARG186/LYS218
E:ASP160-F:ARG248/LYS271
F:ASP101-E:LYS189
With F-chain NSP13.2
E:GLU244-C:LYS70
D:ASP134-E:ARG248
With D-chain NSP8b
E:ASP369-C:ARG21
C:ASP67-E:ARG392/LYS276/LYS394
With C-chain NSP7
E:GLU341-B:ARG96
E:ASP328/GLU353-B:LYS165
With B-chain NSP8a
Table 4.1 The SBs linking E-chain NSP13.1 with ABCDF-chains NSP12-NSP8a-NSP7-NSP8b-NSP13.2 during the six replicates’ (each with 5 .μs) MD simulations
4.3 New Results and Discussions 199
Rep6
Rep5
Rep4
Rep3
Rep2
F:GLU244-E:LYS189/LYS218
B:GLU77-F:ARG15
F:ASP101/ASP105/GLU128-E:LYS189
E:ASP160-F:ARG248
F:ASP369/GLU353-B:ARG96
F:GLU365-A:ARG365
F:ASP435-E:LYS218
E:ASP344/GLU341-F:ARG248
F:ASP101/ASP105/GLU128-E:LYS189
B:ASP101-F:LYS329
A:ASP336-F:ARG390
F:ASP435-E:LYS218
F:ASP101/ASP105/GLU128-E:LYS189 E:ASP160-F:ARG248/LYS271 E:GLU341-F:ARG248
B:ASP78/GLU77-F:LYS94 B:ASP99/ASP101-F:LYS329 F:ASP369-B:ARG96
A:ASP336-F:ARG392
F:GLU365-A:ARG365
E:ASP344/GLU341-F:ARG248 F:ASP435-E:ARG161/LYS218
E:ASP160-F:ARG248/LYS271
B:ASP99-F:LYS329
F:ASP369/GLU353-B:ARG96
F:GLU365-A:ARG365
F:GLU365-E:LYS189
B:ASP101-F:LYS347
B:ASP78/GLU77-F:LYS94
F:GLU128/GLU244-E:LYS189 F:GLU244-E:ARG186/LYS189/LYS218
A:ASP284/ASP303/GLU277-F:LYS189
A:GLU522-F:ARG15/ARG22
A:ASP336-F:ARG390
E:ASP160/GLU156-F:ARG248 F:ASP328/GLU244/GLU353-E:LYS218
A:ASP336-F:ARG390/ARG392/LYS394
F:GLU365-A:ARG365
E:GLU156-F:ARG248
F:ASP369-E:LYS218
E:ASP160-F:ARG248/ARG392/LYS394 F:GLU128/GLU365-E:LYS189
F:ASP101-E:LYS189
B:ASP101-F:LYS347
F:GLU365-A:ARG365 B:ASP112-F:ARG339/LYS189
B:ASP64/GLU60-F:LYS94
A:ASP336-F:ARG392/ARG337/ARG390
E:GLU341-F:ARG248
F:GLU244-E:ARG186/LYS218
F:GLU128-E:LYS189
E:ASP160-F:ARG248/LYS271
With E-chain NSP13.1 F:ASP101-E:LYS189
With D-chain NSP8b
F:GLU365-A:ARG365
With C-chain NSP7
A:ASP336-F:ARG392
Rep1
With B-chain NSP8a
With A-chain NSP12
.\F:
Table 4.2 The SBs linking F-chain NSP13.2 with ABCDE-chains NSP12-NSP8a-NSP7-NSP8b-NSP13.1 during the six replicates’ (each with 5 .μs) MD simulations
200 4 RNA Helicase
4.3 New Results and Discussions
201
NSP13.1, and the SBs within Echain NSP13.1, Fchain NSP13.2, and Achain NSP12, during the six replicates’ (each with 5 .μs) MD simulations. Tables 4.1 and 4.2 can confirm the following SBs: F:ARG248-E:ASP160/GLU 341 (for replicate 5, with HBs F:ARG248.NH2-E:GLU341.OE2 19.38%, E:ARG248.NH2-F:GLU341.OE2 13.64%, F:ARG248.NH2-E:GLU341.OE1 13.16%, F:ARG248.NH1-E:GLU341.OE1 12.92%), E:LYS218-F:GLU244/ASP435 (GLU244 is for replicates 1–3 and ASP435 is for replicates 4–6), E:LYS189F:ASP101/GLU128 (for replicate 4, there is HB E:LYS189.NZ-F:ASP101.OD2 7.42%); A:ASP901-E:LYS94, A:ASP336-F:ARG392/390, A:ARG365-F:GLU365; B:LYS165-E:ASP328/GLU353 for replicates 1–3, and B:ARG96-F:ASP369 for replicates 4–6. However, the SBs B:LYS165-E:ASP328, E:LYS218-F:ASP435, E:LYS218-F:GLU244, and F:ARG248-E:ASP160 are very weak during each 5 .μs MD replicate. We have shown SBs A:ARG365-F:GLU365, F:ARG248-E:GLU341, A:ASP901-E:LYS94, A:ASP336-F:ARG392, B:LYS165-E:GLU353, E:LYS189F:GLU128, E:LYS189-F:ASP101, A:ASP336-F:ARG390, and B:ARG96-F:ASP369 in Fig. 4.4. The SBs A:ARG365-F:GLU365, F:ARG248-E:GLU341, A:ASP901E:LYS94, and A:ASP336-F:ARG392/ARG390 are polar contacts (Table 4.3).
The following SBs within E and within F can be confirmed from Tables 4.7 and 4.8, within E: ASP223-ARG186, ASP315-ARG332, ASP328-LYS347, ASP32LYS28, ASP534-ARG560, ASP583-ARG579, GLU128-LYS131, GLU197-ARG337, GLU201-ARG212, GLU353-LYS347, GLU540-LYS320, ASP204-LYS524/ARG490 (replicates 1–3/4 and 6), and GLU142-ARG409/LYS139 (replicates 1–3/4–6) – all
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these SBs within E-chain NSP13.1 are shown in Fig. 4.5, within F: ASP101-LYS28, ASP223-ARG186, ASP328-LYS347, ASP32-LYS28, ASP369-LYS394, ASP534ARG560 (broken for replicates 1, 5, and 6 (4500–5000 ns)), GLU136-ARG21, GLU142-ARG409, GLU143-LYS146, GLU201-ARG178, GLU244-LYS276, GLU353-LYS347, GLU418-LYS430, GLU420-LYS430, GLU551-LYS477 (broken for replicate 1), ASP315-LYS345/ARG332 (replicates 1–2/4–6), and GLU162LYS524 (replicates 1–3 (but for replicate 2 broken during 1344–3204 ns)) – all these SBs within E-chain NSP13.2 are shown in Fig. 4.6, within both E and F respectively: ASP223-ARG186, ASP328-LYS347, ASP32-LYS28, ASP534-ARG560,
4.4 Concluding Remarks
203
Fig. 4.4 The 13 SBs linking A-, B-, E-, and F-chains (i.e., NSP12 RdRp, NSP8a, NSP13.1, and NSP13.2, respectively) during the six replicates’ MD simulations, where each replicate has 5000 ns MD
and GLU353-LYS347. We also can confirm the following SBs (Tables 4.9 and 4.10) of NSP12 RdRp in Chap. 3: A:ASP170-A:ARG173, A:ASP304-A:ARG640, A:ASP421-A:LYS417, A:ASP465-A:ARG132, A:ASP477-A:ARG640 (for replicate 1 existing only during 3960–5000 ns), A:ASP499-A:ARG513 (broken for replicate 4 during 324–432 ns and for replicate 5 during 684–2388 ns), A:ASP804-A:LYS807, A:GLU136-A:LYS783 (broken for replicates 4–6), A:GLU180-A:ARG183 (broken for replicate 4), A:GLU474-A:ARG305 (always broken), A:GLU474-A:ARG640 (broken for replicate 1 during 4236–5000 ns), and A:GLU744-A:ARG726 (broken for replicate 2 during 1860–3156 ns and for replicate 3 during 4308–5000 ns) – all these SBs within A-chain NSP12 RaRp are shown in Fig. 4.7. The SBs A:ASP274/269-B:ARG111 and A:ARG331-B:ASP112 between RdRp and NSP8a and an SB C:ASP38-C:LYS51 within NSP7 are shown in Fig. 4.8. All these SBs within C-chain, linking A-chain and B-chain, within A-chain, within E-chain, and within F-chain at the same time own strong or weak HBs – we list them with occupancy rates (.≥10%) in Tables 4.4, 4.5, and 4.6.
4.4 Concluding Remarks NSP13 RNA helicase is a SARS-CoV-2 antiviral target. This chapter presents the bioinformatics of polar contacts within NSP13.1: E:ASP223-E:ARG186, E:ASP315-E:ARG332, E:ASP328-E:LYS347, E:ASP32-E:LYS28, E:ASP534E:ARG560, E:ASP583-E:ARG579, E:GLU128-E:LYS131, E:GLU197-E:ARG337, E:GLU201-E:ARG212, E:GLU353-E:LYS347, E:GLU540-E:LYS320, E:ASP204E:LYS524, E:ASP204-E:ARG490, E:GLU142-E:ARG409, E:GLU142-E:LYS139 and within NSP13.2: F:ASP101-F:LYS28, F:ASP223-F:ARG186, F:ASP328F:LYS347, F:ASP32-F:LYS28, F:ASP369-F:LYS394, F:ASP534-F:ARG560, F:GLU136-F:ARG21, F:GLU142-F:ARG409, F:GLU143-F:LYS146, F:GLU201F:ARG178, F:GLU244-F:LYS276, F:GLU353-F:LYS347, F:GLU418-F:LYS430, F:GLU420-F:LYS430, F:GLU551-F:LYS477, F:GLU162-F:LYS524, F:ASP315F:LYS345, and F:ASP315-F:F:ARG332 of the SARS-CoV-2-NSP13 RNA helicase in its optimized structure and confirmed in its six replicates (each replicate has 5 .μs’ long) of MD simulations. During the long MD of each of the six replicates, the polar contacts among NSP13.1, NSP13.2, RdRp NSP13, NSP7, NSP8a, and
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4 RNA Helicase
NSP8b are also studied in this chapter. Other structural bioinformatics for NSP13 helicase such as .π -interactions F:HID245-E:LYS218.NZ+, etc. are also presented in this chapter.
LYS94.NZ-ASP901.OD2 10.53%
Rep2
LYS94.NZ-ASP901.OD1 11.72%
LYS94.NZ-ASP901.OD2 13.64%
ARG390.NH2-ASP336.OD1 11.96%
ARG390.NH1-ASP336.OD1 20.10%
ARG390.NH2-ASP336.OD2 21.77%
LYS94.NZ-ASP901.OD2 11.72%
LYS94.NZ-ASP901.OD1 13.88%
ARG365.NE-GLU365.OE1 10.05%
ARG365.NE-GLU365.OE2 10.77%
ARG392.NH1-ASP336.OD1 11.48%
ARG392.NH2-ASP336.OD2 12.68%
ARG248.NH1-GLU341.OE1 12.92%
ARG248.NH2-GLU341.OE1 13.16%
ARG248.NH2-GLU341.OE2 19.38%
ARG365.NH2-GLU365.OE2 13.40%
ARG365.NH2-GLU365.OE1 16.03%
ARG365.NH2-GLU365.OE2 11.00%
ARG365.NH2-GLU365.OE1 18.90% ARG365.NH2-GLU365.OE2 15.79%
ARG365.NH2-GLU365.OE1 16.99%
ARG365.NH2-GLU365.OE2 16.27%
ARG365.NH2-GLU365.OE1 15.07%
Rep6
Rep5
Rep4
Rep3
Table 4.3 The HBs (with occupancy rates .≥10) of the SB A:ARG365-F:GLU365, F:ARG248-E:GLU341, A:ASP901-E:LYS94, A:ASP336-F:ARG392, and A:ASP336-F:ARG390 linking A-, E-, and F-chains (i.e., NSP12 RdRp, NSP13.1, and NSP13.2, respectively) during the six replicates’ (each with 5 .μs) MD simulations
4.4 Concluding Remarks 205
ARG111.NH1-ASP274.OD1 14.11
ARG111.NH1-ASP274.OD1 18.42
ARG640.NH2-ASP304.OD1 27.27 ASP421.N-LYS417.O 55.74 LYS417.NZ-ASP421.OD1 30.86 LYS417.NZ-ASP421.OD2 23.44 ARG132.NH2-ASP465.OD2 46.89
ARG640.NH2-ASP304.OD2 35.89 ASP421.N-LYS417.O 57.42 LYS417.NZ-ASP421.OD2 39.23 LYS417.NZ-ASP421.OD1 19.38 ARG132.NH2-ASP465.OD2 67.7
ARG640.NH1-ASP477.OD1 27.99 ARG513.NE-ASP499.OD2 44.26
ARG173.NH2-ASP170.OD2 37.56
ARG173.NH2-ASP170.OD1 30.38
ARG173.NE-ASP170.OD2 30.14
ARG640.NE-ASP304.OD2 58.13
ARG640.NH2-ASP304.OD1 51.91
ARG640.NE-ASP304.OD1 28.95
ARG640.NH2-ASP304.OD2 26.79
ASP421.N-LYS417.O 56.70
LYS417.NZ-ASP421.OD2 32.06
LYS417.NZ-ASP421.OD1 22.25
ARG132.NH2-ASP465.OD2 75.36
ARG640.NH1-ASP477.OD1 29.90
ARG640.NH1-ASP477.OD2 28.23
ARG513.NE-ASP499.OD1 44.98
ARG513.NE-ASP499.OD2 42.11
ARG513.NH2-ASP499.OD1 41.87
ARG513.NH2-ASP499.OD2 40.19
LYS783.NZ-GLU136.OE1 33.01
LYS783.NZ-GLU136.OE2 32.54
ARG173.NH2-ASP170.OD1 40.91
ARG173.NE-ASP170.OD1 33.49
ARG173.NH2-ASP170.OD2 32.06
ARG640.NE-ASP304.OD2 41.63
ARG640.NH2-ASP304.OD1 39.23
ARG640.NE-ASP304.OD1 27.03
ARG640.NH2-ASP304.OD2 24.88
ASP421.N-LYS417.O 56.46
LYS417.NZ-ASP421.OD1 30.86
LYS417.NZ-ASP421.OD2 22.73
ARG132.NH2-ASP465.OD2 69.62
ARG640.NH1-ASP477.OD2 23.21
ARG640.NH1-ASP477.OD1 22.73
ARG513.NE-ASP499.OD1 46.41
ARG513.NH2-ASP499.OD2 42.58
ARG513.NE-ASP499.OD2 40.43
ARG513.NH2-ASP499.OD1 38.04
LYS783.NZ-GLU136.OE2 30.38
LYS783.NZ-GLU136.OE1 23.92
LYS783.NZ-GLU136.OE2 22.97
LYS783.NZ-GLU136.OE1 25.12
ARG513.NH2-ASP499.OD2 36.84
ARG513.NH2-ASP499.OD1 41.15
ARG513.NE-ASP499.OD1 43.06
ARG640.NH1-ASP477.OD2 28.23
ARG640.NH2-ASP304.OD1 40.91
ARG640.NE-ASP304.OD1 40.91
ARG640.NE-ASP304.OD2 46.65
ARG173.NE-ASP170.OD2 33.01
ARG173.NH2-ASP170.OD1 33.73
ARG513.NH2-ASP499.OD1 37.80
ARG513.NH2-ASP499.OD2 39.23
ARG513.NE-ASP499.OD2 41.63
ARG513.NE-ASP499.OD1 42.11
ARG640.NH1-ASP477.OD1 25.60
ARG640.NH1-ASP477.OD2 29.67
ARG132.NH1-ASP465.OD2 18.42
ARG640.NE-ASP304.OD2 36.84
ARG640.NH2-ASP304.OD2 37.56
ARG640.NE-ASP304.OD1 48.56
ARG173.NE-ASP170.OD1 22.49
ARG173.NH2-ASP170.OD2 25.60
ARG173.NE-ASP170.OD2 27.99
ARG173.NH2-ASP170.OD1 29.43
ARG173.NH2-ASP170.OD2 40.91
ARG173.NE-ASP170.OD1 37.80 ARG173.NE-ASP170.OD1 37.32
VAL115.N-VAL330.O 14.83
VAL115.N-VAL330.O 15.07
VAL115.N-VAL330.O 18.42
VAL330.N-VAL115.O 73.21
VAL330.N-VAL115.O 50.00
VAL330.N-VAL115.O 55.74
VAL115.N-VAL330.O 16.51
ARG111.NH2-ASP274.OD1 11.96
ARG111.NH2-ASP274.OD2 13.40
ARG173.NE-ASP170.OD2 42.11
VAL330.N-VAL115.O 57.42
ARG331.NH2-ASP112.OD1 11.96
ARG331.NH2-ASP112.OD2 13.40
ARG111.NH1-ASP274.OD2 13.40
ARG331.NH2-ASP112.OD2 13.88
ARG331.NH2-ASP112.OD1 16.27
ARG331.NH1-ASP112.O 10.53
ARG331.NH1-ASP112.O 13.88
ARG513.NH2-ASP499.OD2 25.12
ARG513.NH2-ASP499.OD1 26.08
ARG513.NE-ASP499.OD1 27.03
ARG513.NE-ASP499.OD2 29.19
ARG640.NH1-ASP477.OD2 16.75
ARG640.NH1-ASP477.OD1 18.90
ARG132.NH2-ASP465.OD2 53.83
LYS417.NZ-ASP421.OD1 23.68
LYS417.NZ-ASP421.OD2 34.45
ASP421.N-LYS417.O 52.39
ARG640.NH2-ASP304.OD1 31.10
ARG640.NH2-ASP304.OD2 33.73
ARG640.NE-ASP304.OD2 42.82
ARG640.NE-ASP304.OD1 45.93
ARG173.NE-ASP170.OD1 10.77
ARG173.NH2-ASP170.OD1 12.92
ARG173.NH2-ASP170.OD2 15.55
VAL115.N-VAL330.O 24.40
VAL330.N-VAL115.O 67.46
LYS51.NZ-ASP38.OD2 18.42
ARG513.NH2-ASP499.OD2 31.1
ARG513.NE-ASP499.OD1 35.65
ARG513.NH2-ASP499.OD1 46.17
ARG513.NE-ASP499.OD2 48.09
ARG640.NH1-ASP477.OD1 14.35
ARG640.NH1-ASP477.OD2 21.05
ARG132.NH2-ASP465.OD2 53.83
LYS417.NZ-ASP421.OD1 24.16
LYS417.NZ-ASP421.OD2 33.01
ASP421.N-LYS417.O 50.48
ARG640.NH2-ASP304.OD2 23.44
ARG640.NH2-ASP304.OD1 29.90
ARG640.NE-ASP304.OD1 34.69
ARG640.NE-ASP304.OD2 43.30
ARG173.NH2-ASP170.OD1 30.62
ARG173.NE-ASP170.OD2 32.78
ARG173.NH2-ASP170.OD2 40.19
ARG173.NE-ASP170.OD1 40.91
VAL115.N-VAL330.O 16.27
VAL330.N-VAL115.O 58.13
LYS51.NZ-ASP38.OD1 22.49
LYS51.NZ-ASP38.OD2 23.21
LYS51.NZ-ASP38.OD1 23.92
Rep6
LYS51.NZ-ASP38.OD2 20.33
LYS51.NZ-ASP38.OD1 29.67
Rep5
LYS51.NZ-ASP38.OD1 22.25
LYS51.NZ-ASP38.OD2 26.79
Rep4
LYS51.NZ-ASP38.OD2 26.79
LYS51.NZ-ASP38.OD1 27.27
LYS51.NZ-ASP38.OD2 25.84
LYS51.NZ-ASP38.OD1 29.67
Rep3
Rep2
Rep1
Table 4.4 The HBs (with occupancy rates .≥10%) of SBs C:ASP38-C:LYS51 within C-chain, A:ARG331-B:ASP112, A:ASP274-B:ARG111, and A:VAL330-B:VAL115 linking AB chains, and A:ASP170-A:ARG173, A:ASP304-A:ARG640, A:ASP421-A:LYS417, A:ASP465-A:ARG132, A:ASP477A:ARG640, A:ASP499-A:ARG513, A:GLU136-A:LYS783, A:GLU180-A:ARG183, A:GLU474-A:ARG305, A:GLU474-A:ARG640, and A:GLU744A:ARG726 within A-chain (i.e., within NSP7, linking NSP12 RdRp and NSP8a, within NSP12 RdRp) during the six replicates’ (each with 5 .μs) MD simulations
206 4 RNA Helicase
ARG305.NE-GLU474.OE1 36.36
ARG305.NE-GLU474.OE1 47.61
ARG305.NH1-GLU474.OE1 9.57
ARG640.NH2-GLU474.OE1 80.62
ARG640.NH1-GLU474.OE2 72.49
ARG305.NE-GLU474.OE2 39.95
ARG305.NE-GLU474.OE1 27.03
ARG640.NH2-GLU474.OE2 45.45
ARG640.NH1-GLU474.OE1 43.54 ARG640.NH1-GLU474.OE1 35.17 ARG726.NH1-GLU744.OE2 44.02
ARG726.NH2-GLU744.OE2 34.21
ARG726.NH1-GLU744.OE1 32.78
ARG726.NH1-GLU744.OE2 31.58
ARG726.NH2-GLU744.OE1 31.10
ARG640.NH1-GLU474.OE2 29.67
ARG726.NH1-GLU744.OE1 43.78
ARG726.NH2-GLU744.OE2 43.78
ARG726.NH2-GLU744.OE1 40.19
ARG726.NH1-GLU744.OE2 39.71 ARG726.NH2-GLU744.OE2 36.60
ARG726.NH1-GLU744.OE1 39.47
ARG726.NH2-GLU744.OE1 40.67
ARG640.NH2-GLU474.OE2 35.41
ARG640.NH2-GLU474.OE1 32.54
ARG640.NH1-GLU474.OE2 48.80
ARG640.NH2-GLU474.OE1 49.28
ARG305.NE-GLU474.OE2 13.40
ARG183.NH2-GLU180.OE2 16.03
ARG183.NH2-GLU180.OE1 39.71
ARG183.NH2-GLU180.OE1 69.14
ARG183.NE-GLU180.OE2 72.25 ARG183.NE-GLU180.OE1 17.22
ARG183.NH2-GLU180.OE2 86.36
ARG183.NE-GLU180.OE2 40.43
ARG183.NE-GLU180.OE1 89.23
ARG183.NE-GLU180.OE1 46.65
ARG183.NH2-GLU180.OE2 44.74
ARG726.NH1-GLU744.OE2 38.52
ARG726.NH2-GLU744.OE1 39.71
ARG726.NH2-GLU744.OE2 45.93
ARG726.NH1-GLU744.OE1 46.89
ARG640.NH1-GLU474.OE2 33.73
ARG640.NH2-GLU474.OE1 36.60
ARG640.NH1-GLU474.OE1 43.06
ARG640.NH2-GLU474.OE2 44.02
ARG305.NE-GLU474.OE1 9.81
ARG305.NE-GLU474.OE2 17.94
ARG183.NE-GLU180.OE1 13.88
ARG183.NH2-GLU180.OE2 16.51
ARG183.NE-GLU180.OE2 22.25
ARG183.NH2-GLU180.OE1 23.68
ARG726.NH1-GLU744.OE1 39.95
ARG726.NH2-GLU744.OE2 40.67
ARG726.NH1-GLU744.OE2 46.17
ARG726.NH2-GLU744.OE1 46.89
ARG640.NH1-GLU474.OE2 37.32
ARG640.NH2-GLU474.OE1 38.04
ARG640.NH2-GLU474.OE2 41.15
ARG640.NH1-GLU474.OE1 44.98
ARG183.NH2-GLU180.OE2 10.53
ARG183.NE-GLU180.OE1 11.00
ARG183.NH2-GLU180.OE1 73.21
ARG183.NE-GLU180.OE2 80.14
ARG726.NH1-GLU744.OE2 40.67
ARG726.NH2-GLU744.OE1 42.82
ARG726.NH1-GLU744.OE1 43.30
ARG726.NH2-GLU744.OE2 43.78
ARG640.NH2-GLU474.OE1 30.14
ARG640.NH1-GLU474.OE2 30.86
ARG640.NH2-GLU474.OE2 47.61
ARG640.NH1-GLU474.OE1 50.00
ARG183.NH2-GLU180.OE2 29.90
ARG183.NE-GLU180.OE1 32.06
ARG183.NH2-GLU180.OE1 55.74
ARG183.NE-GLU180.OE2 60.77
4.4 Concluding Remarks 207
ARG186.NE-ASP223.OD1 98.80
ARG186.NH2-ASP223.OD2 99.04
ARG186.NE-ASP223.OD1 98.56
ASP223.OD2-ARG186.NH2 90.43
ARG332.NH2-ASP315.OD1 26.32
ARG332.NE-ASP315.OD2 23.68
ARG332.NE-ASP315.OD1 18.18
ARG186.NH2-ASP223.OD2 99.76
ARG186.NE-ASP223.OD1 97.61
ASP223.OD2-ARG186.NH2 87.80
ARG332.NH2-ASP315.OD2 32.30
ARG332.NH2-ASP315.OD1 26.79
ARG332.NE-ASP315.OD1 16.51
LYS28.NZ-ASP32.OD2 36.12
ASP32.N-LYS28.O 33.25
ARG560.NE-ASP534.OD2 61.96
ARG560.NE-ASP534.OD1 60.77
ARG560.NH2-ASP534.OD2 36.84
ARG560.NH2-ASP534.OD1 33.49
ASP583.N-ARG579.O 34.45
ARG579.NE-ASP583.OD2 22.25
ARG579.NE-ASP583.OD1 20.10
ARG579.NH2-ASP583.OD1 13.40
ARG579.NH2-ASP583.OD2 12.92
LYS28.NZ-ASP32.OD1 46.41
LYS28.NZ-ASP32.OD2 39.47
ARG560.NE-ASP534.OD1 61.72
ARG560.NE-ASP534.OD2 45.45
ARG560.NH2-ASP534.OD2 42.34
ARG560.NH2-ASP534.OD1 36.60
ASP583.N-ARG579.O 34.69
ARG579.NE-ASP583.OD2 22.25
ARG579.NE-ASP583.OD1 21.29
ARG579.NH2-ASP583.OD2 12.68
ARG579.NH2-ASP583.OD1 11.24
LYS347.NZ-ASP328.OD2 14.11
LYS347.NZ-ASP328.OD1 19.14
LYS347.NZ-ASP328.O 11.24
ARG579.NH2-ASP583.OD1 10.53
ARG579.NH1-ASP583.OD2 10.77
ARG579.NH2-ASP583.OD2 12.68
ARG579.NE-ASP583.OD2 20.33
ARG579.NE-ASP583.OD1 20.33
ASP583.N-ARG579.O 33.49
ARG560.NH2-ASP534.OD1 59.33
ARG560.NH2-ASP534.OD2 62.44
ARG560.NE-ASP534.OD2 63.40
ARG560.NE-ASP534.OD1 64.59
LYS28.NZ-ASP32.OD1 34.93
ASP32.N-LYS28.O 38.76
LYS28.NZ-ASP32.OD2 43.78
ARG579.NH2-ASP583.OD2 12.68
ARG579.NH2-ASP583.OD1 13.88
ARG579.NE-ASP583.OD1 18.66
ARG579.NE-ASP583.OD2 18.90
ARG579.NH2-ASP583.OD1 9.81
ARG579.NH2-ASP583.OD2 12.44
ARG579.NE-ASP583.OD2 17.46
ARG579.NE-ASP583.OD1 19.86
ASP583.N-ARG579.O 39.71
ARG579.NH2-ASP583.OD1 12.92
ARG579.NH2-ASP583.OD2 17.46
ARG579.NE-ASP583.OD2 21.05
ARG579.NE-ASP583.OD1 22.49
ASP583.N-ARG579.O 41.15
ARG560.NH1-ASP534.OD2 15.79
ASP583.N-ARG579.O 40.91
ARG560.NH1-ASP534.OD1 19.14
ARG560.NE-ASP534.OD1 33.49
ARG560.NH2-ASP534.OD2 41.15
ARG560.NE-ASP534.OD2 51.91
ARG560.NH2-ASP534.OD1 53.35
LYS28.NZ-ASP32.OD1 34.69
LYS28.NZ-ASP32.OD2 37.56
ASP32.N-LYS28.O 39.00
LYS347.NZ-ASP328.OD1 22.25
LYS347.NZ-ASP328.OD2 22.25
LYS347.NZ-ASP328.O 26.56
ARG332.NH1-ASP315.OD1 11.96
ARG332.NH2-ASP315.OD1 63.64
ARG186.NE-ASP223.OD1 98.56
ARG186.NH2-ASP223.OD2 99.04
Rep6
ARG560.NH1-ASP534.OD2 10.29
ARG560.NE-ASP534.OD1 29.43
ARG560.NE-ASP534.OD2 31.10
ARG560.NH2-ASP534.OD2 38.52
ARG560.NH2-ASP534.OD1 44.26
LYS28.NZ-ASP32.OD2 31.10
LYS28.NZ-ASP32.OD1 42.82
ASP32.N-LYS28.O 47.13
LYS347.NZ-ASP328.OD2 20.33
LYS347.NZ-ASP328.OD1 21.77
LYS347.NZ-ASP328.O 23.92
ARG332.NH2-ASP315.OD1 66.03
ARG186.NE-ASP223.OD1 97.85
ARG186.NH2-ASP223.OD2 99.76
Rep5
ARG560.NH1-ASP534.OD1 22.49
ARG560.NE-ASP534.OD2 38.04
ARG560.NH2-ASP534.OD1 47.37
ARG560.NE-ASP534.OD1 52.87
ARG560.NH2-ASP534.OD2 67.22
LYS28.NZ-ASP32.OD2 32.06
LYS28.NZ-ASP32.OD1 32.54
ASP32.N-LYS28.O 43.30
LYS347.NZ-ASP328.OD1 21.05
LYS28.NZ-ASP32.OD1 42.11
LYS347.NZ-ASP328.O 24.16
LYS347.NZ-ASP328.OD2 22.97
LYS347.NZ-ASP328.OD1 27.27
LYS347.NZ-ASP328.OD1 27.75
ASP32.N-LYS28.O 47.13
ARG332.NH1-ASP315.OD1 12.20
LYS347.NZ-ASP328.OD2 28.71 LYS347.NZ-ASP328.O 42.34
ARG332.NH2-ASP315.OD2 17.94
ARG332.NH1-ASP315.OD2 14.59
ARG332.NH2-ASP315.OD2 30.86
ARG332.NH2-ASP315.OD1 43.78
ARG186.NE-ASP223.OD1 96.89
ARG186.NH2-ASP223.OD2 99.28
Rep4
LYS347.NZ-ASP328.OD2 30.14
ARG332.NE-ASP315.OD2 33.25
ARG332.NH2-ASP315.OD1 42.58
ARG332.NH2-ASP315.OD2 65.55
ASP223.OD2-ARG186.NH2 90.67
ARG186.NH2-ASP223.OD2 98.80
Rep3
Rep2
Rep1
Table 4.5 The HBs (with occupancy rates .≥10%) of SBs E:ASP223-E:ARG186, E:ASP315-E:ARG332, E:ASP328-E:LYS347, E:ASP32-E:LYS28, E:ASP534-E:ARG560, E:ASP583-E:ARG579, E:GLU128-E:LYS131, E:GLU197-E:ARG337, E:GLU201-E:ARG212, E:GLU353-E:LYS347, E:GLU540E:LYS320, E:ASP204-E:LYS524, E:ASP204-E:ARG490, E:GLU142-E:ARG409, and E:GLU142-E:LYS139 within E chain (i.e., within NSP13.1) during the six replicates’ (each with 5 .μs) MD simulations
208 4 RNA Helicase
ARG337.NH1-GLU197.OE1 18.66
ARG337.NE-GLU197.OE2 15.79
ARG337.NE-GLU197.OE1 15.31
ARG212.NH1-GLU201.OE2 34.93
ARG212.NH1-GLU201.OE1 28.71
LYS347.NZ-GLU353.OE1 56.22
LYS347.NZ-GLU353.OE2 41.15
ARG337.NH1-GLU197.OE1 42.11
ARG337.NH1-GLU197.OE2 34.21
ARG337.NE-GLU197.OE1 31.34
ARG212.NH1-GLU201.OE2 10.53
ARG212.NH1-GLU201.OE1 10.05
LYS347.NZ-GLU353.OE2 52.87
LYS347.NZ-GLU353.OE1 51.20 LYS347.NZ-GLU353.OE1 52.63
LYS347.NZ-GLU353.OE2 54.55
ARG212.NH1-GLU201.OE1 27.75
ARG212.NH1-GLU201.OE2 29.19
ARG337.NH1-GLU197.OE2 50.48
ARG337.NE-GLU197.OE1 53.11
ARG337.NE-GLU197.OE2 58.13
ARG337.NH1-GLU197.OE1 58.85
LYS131.NZ-GLU128.OE1 39.00
LYS524.NZ-ASP204.OD2 41.15
ARG409.NE-GLU142.OE2 83.25
ARG409.NH2-GLU142.OE1 81.34
ARG409.NH2-GLU142.OE2 47.13
ARG409.NE-GLU142.OE1 36.60
GLU142.OE2-ARG409.NH2 31.58
LYS524.NZ-ASP204.OD2 54.31
ARG409.NE-GLU142.OE2 65.31
ARG409.NH2-GLU142.OE1 57.18
ARG409.NE-GLU142.OE1 55.74
ARG409.NH2-GLU142.OE2 48.09
GLU142.OE2-ARG409.NH2 26.56 LYS139.NZ-GLU142.OE2 31.34 LYS139.NZ-GLU142.OE1 30.38
LYS139.NZ-GLU142.OE1 13.88
ARG409.NE-GLU142.OE2 19.14
ARG409.NE-GLU142.OE1 20.33
ARG409.NH2-GLU142.OE1 24.40
ARG409.NH2-GLU142.OE2 26.56
LYS139.NZ-GLU142.OE2 14.11
GLU142.OE2-ARG409.NH2 38.52
ARG409.NH2-GLU142.OE1 55.50
ARG409.NH2-GLU142.OE2 57.18
ARG409.NE-GLU142.OE2 58.13
ARG409.NE-GLU142.OE1 60.53
ARG490.NE-ASP204.OD1 69.86 ARG490.NH2-ASP204.OD2 68.66
ARG490.NH2-ASP204.OD2 11.24
LYS320.NZ-GLU540.OE2 47.61
LYS139.NZ-GLU142.OE1 12.68
LYS139.NZ-GLU142.OE2 14.83
ARG409.NE-GLU142.OE1 37.56
ARG409.NH2-GLU142.OE2 41.39
ARG409.NH2-GLU142.OE1 45.69
ARG409.NE-GLU142.OE2 45.93
ARG490.NH2-ASP204.OD2 81.10
ARG490.NE-ASP204.OD1 88.52
LYS320.NZ-GLU540.OE1 41.63
LYS139.NZ-GLU142.OE1 24.88
LYS139.NZ-GLU142.OE2 26.32
ARG409.NE-GLU142.OE2 27.03
ARG409.NE-GLU142.OE1 28.71
ARG409.NH2-GLU142.OE1 30.86
ARG409.NH2-GLU142.OE2 37.56
ARG490.NH2-ASP204.OD2 39.00
ARG490.NE-ASP204.OD1 40.91
LYS320.NZ-GLU540.OE2 12.92
LYS320.NZ-GLU540.OE1 36.36
LYS347.NZ-GLU353.OE1 47.61
LYS347.NZ-GLU353.OE2 58.85
ARG212.NH1-GLU201.OE1 12.68 LYS347.NZ-GLU353.OE2 47.37
ARG212.NH1-GLU201.OE1 21.29 LYS347.NZ-GLU353.OE1 53.11
LYS347.NZ-GLU353.OE2 54.55
ARG212.NH2-GLU201.OE1 22.25 ARG212.NH1-GLU201.OE2 12.92
ARG212.NE-GLU201.OE2 22.73
ARG212.NH2-GLU201.OE2 23.92
ARG212.NE-GLU201.OE1 27.03
ARG337.NH1-GLU197.OE1 46.17
ARG337.NE-GLU197.OE2 47.13
ARG337.NE-GLU197.OE1 48.09
ARG337.NH1-GLU197.OE2 51.67
LYS131.NZ-GLU128.OE2 42.82
ARG212.NE-GLU201.OE2 24.88
LYS347.NZ-GLU353.OE1 52.87
ARG212.NH1-GLU201.OE2 14.83
ARG212.NH1-GLU201.OE1 15.31
ARG337.NH1-GLU197.OE1 34.93
ARG337.NE-GLU197.OE2 36.36
ARG337.NH1-GLU197.OE2 39.71
ARG337.NE-GLU197.OE1 41.63
LYS131.NZ-GLU128.OE1 36.60
ARG212.NH2-GLU201.OE2 22.73
ARG212.NH2-GLU201.OE1 25.12
ARG212.NE-GLU201.OE1 25.84
ARG212.NH1-GLU201.OE2 26.56
ARG337.NH1-GLU197.OE2 42.11
ARG337.NE-GLU197.OE1 44.98
ARG337.NH1-GLU197.OE1 49.52
ARG337.NE-GLU197.OE2 49.76
LYS131.NZ-GLU128.OE2 37.56
ARG490.NH1-ASP204.OD1 12.20
LYS524.NZ-ASP204.OD2 48.56
LYS320.NZ-GLU540.OE1 21.05 LYS524.NZ-ASP204.OD1 50.96
LYS524.NZ-ASP204.OD1 47.13
LYS320.NZ-GLU540.OE2 15.79
LYS524.NZ-ASP204.OD1 54.31
LYS320.NZ-GLU540.OE2 23.21
ARG337.NH1-GLU197.OE2 19.14
ARG337.NE-GLU197.OE2 43.06
LYS320.NZ-GLU540.OE1 47.13
LYS131.NZ-GLU128.OE2 33.01
LYS131.NZ-GLU128.OE2 35.89
4.4 Concluding Remarks 209
LYS347.NZ-ASP328.OD1 21.05 LYS347.NZ-ASP328.OD2 14.11
LYS347.NZ-ASP328.OD2 22.97 LYS347.NZ-ASP328.OD1 19.14
ASP223.OD2-ARG186.NH2 90.43
LYS347.NZ-ASP328.OD2 28.71
LYS347.NZ-ASP328.OD1 27.27
LYS347.NZ-ASP328.O 11.24
ASP223.OD2-ARG186.NH2 87.80
LYS347.NZ-ASP328.OD2 30.14
LYS347.NZ-ASP328.OD1 27.75
ARG21.NE-GLU136.OE1 50.48
ARG409.NE-GLU142.OE2 83.25
ARG409.NH2-GLU142.OE1 81.34
ARG409.NH2-GLU142.OE2 47.13
ARG409.NE-GLU142.OE1 36.60
LYS146.NZ-GLU143.OE2 57.42
LYS146.NZ-GLU143.OE1 48.56
ARG21.NE-GLU136.OE2 34.21
ARG409.NE-GLU142.OE2 65.31
ARG409.NH2-GLU142.OE1 57.18
ARG409.NE-GLU142.OE1 55.74
ARG409.NH2-GLU142.OE2 48.09
LYS146.NZ-GLU143.OE2 54.55
LYS146.NZ-GLU143.OE1 48.09
ARG178.NH2-GLU201.OE2 25.60
ARG21.NE-GLU136.OE2 56.46
ARG21.NE-GLU136.OE1 49.04
ARG178.NH2-GLU201.OE2 34.93
ARG178.NE-GLU201.OE2 41.63
ARG560.NH2-ASP534.OD1 33.49
ARG560.NH2-ASP534.OD1 36.60
ARG178.NH2-GLU201.OE1 31.34
ARG560.NH2-ASP534.OD2 36.84
ARG560.NH2-ASP534.OD2 42.34
ARG178.NE-GLU201.OE2 39.00
LYS146.NZ-GLU143.OE1 51.91
ARG560.NE-ASP534.OD1 60.77
ARG560.NE-ASP534.OD2 45.45
ARG178.NE-GLU201.OE1 35.41
ARG409.NE-GLU142.OE1 60.53
ARG560.NE-ASP534.OD2 61.96
ARG178.NE-GLU201.OE1 48.09
ARG21.NE-GLU136.OE1 52.63
LYS394.NZ-ASP369.OD1 19.14
LYS394.NZ-ASP369.OD1 12.68
ARG560.NE-ASP534.OD1 61.72
ARG178.NH2-GLU201.OE1 48.09
LYS394.NZ-ASP369.OD2 22.25
LYS394.NZ-ASP369.OD2 17.70
LYS394.NZ-ASP369.OD2 21.05
LYS394.NZ-ASP369.OD2 14.59
ARG178.NE-GLU201.OE2 65.31
LYS394.NZ-ASP369.OD1 29.19
LYS394.NZ-ASP369.OD1 18.18
ASP32.N-LYS28.O 33.25
ARG178.NH2-GLU201.OE2 28.23
ARG178.NH2-GLU201.OE1 30.86
ARG178.NE-GLU201.OE1 38.04
LYS146.NZ-GLU143.OE2 41.87
ARG178.NH2-GLU201.OE2 22.25
ARG178.NH2-GLU201.OE1 22.49
ARG178.NE-GLU201.OE2 28.23
ARG178.NE-GLU201.OE1 31.82
LYS146.NZ-GLU143.OE1 37.32
ARG409.NE-GLU142.OE2 19.14
LYS146.NZ-GLU143.OE2 52.63
ARG409.NE-GLU142.OE1 20.33
ARG409.NH2-GLU142.OE1 24.40
ARG409.NH2-GLU142.OE2 26.56
ARG21.NE-GLU136.OE1 20.81
ARG21.NE-GLU136.OE2 43.30
ARG21.NE-GLU136.OE2 57.18
ARG178.N-GLU201.OE2 10.77
ARG178.NH2-GLU201.OE2 32.78
ARG178.NH2-GLU201.OE1 35.17
ARG178.NE-GLU201.OE1 46.41
ARG178.NE-GLU201.OE2 50.96
LYS146.NZ-GLU143.OE1 48.80
LYS146.NZ-GLU143.OE2 64.59
ARG409.NE-GLU142.OE1 37.56
ARG409.NH2-GLU142.OE2 41.39
ARG409.NH2-GLU142.OE1 45.69
ARG409.NE-GLU142.OE2 45.93
ARG21.NE-GLU136.OE1 52.15
ARG178.NH2-GLU201.OE1 25.12
ARG178.NH2-GLU201.OE2 27.75
ARG178.NE-GLU201.OE1 32.78
ARG178.NE-GLU201.OE2 34.45
LYS146.NZ-GLU143.OE1 48.80
LYS146.NZ-GLU143.OE2 50.48
ARG409.NE-GLU142.OE2 27.03
ARG409.NE-GLU142.OE1 28.71
ARG409.NH2-GLU142.OE1 30.86
ARG409.NH2-GLU142.OE2 37.56
ARG21.NE-GLU136.OE2 34.45
ARG21.NE-GLU136.OE1 44.02
ARG560.NH1-ASP534.OD1 19.14 ARG560.NH1-ASP534.OD2 15.79
ARG560.NE-ASP534.OD1 33.49
ARG560.NH2-ASP534.OD2 41.15
ARG560.NE-ASP534.OD2 51.91
ARG560.NH2-ASP534.OD1 53.35
LYS394.NZ-ASP369.OD1 28.71
LYS394.NZ-ASP369.OD2 29.90
LYS28.NZ-ASP32.OD1 34.69
LYS28.NZ-ASP32.OD2 37.56
ASP32.N-LYS28.O 39.00
LYS347.NZ-ASP328.OD1 22.25
LYS347.NZ-ASP328.OD2 22.25
LYS347.NZ-ASP328.O 26.56
ARG186.NE-ASP223.OD1 98.56
ARG186.NH2-ASP223.OD2 99.04
ARG560.NH1-ASP534.OD2 10.29
ARG560.NE-ASP534.OD1 29.43
ARG560.NE-ASP534.OD2 31.10
ARG560.NH2-ASP534.OD2 38.52
ARG560.NH2-ASP534.OD1 44.26
LYS394.NZ-ASP369.OD2 34.69
LYS394.NZ-ASP369.OD1 34.69
LYS28.NZ-ASP32.OD2 31.10
LYS28.NZ-ASP32.OD1 42.82
ASP32.N-LYS28.O 47.13
LYS347.NZ-ASP328.OD2 20.33
LYS347.NZ-ASP328.OD1 21.77
LYS347.NZ-ASP328.O 23.92
ARG186.NE-ASP223.OD1 97.85
ARG186.NH2-ASP223.OD2 99.76
LYS28.NZ-ASP101.OD2 14.83
LYS28.NZ-ASP101.OD1 18.66
Rep6
ARG560.NH1-ASP534.OD1 22.49
ARG560.NE-ASP534.OD2 38.04
ARG560.NH2-ASP534.OD1 47.37
ARG560.NE-ASP534.OD1 52.87
ARG560.NH2-ASP534.OD2 67.22
LYS28.NZ-ASP32.OD2 32.06
ARG409.NH2-GLU142.OE1 55.50
ARG409.NH2-GLU142.OE2 57.18
ARG409.NE-GLU142.OE2 58.13
ARG21.NE-GLU136.OE2 57.18
ARG560.NH2-ASP534.OD1 59.33
ARG560.NH2-ASP534.OD2 62.44
ARG560.NE-ASP534.OD2 63.40
ARG560.NE-ASP534.OD1 64.59
LYS28.NZ-ASP32.OD1 34.93
LYS28.NZ-ASP32.OD1 32.54
ASP32.N-LYS28.O 43.30
LYS28.NZ-ASP32.OD2 39.47
ASP32.N-LYS28.O 38.76
LYS28.NZ-ASP32.OD2 36.12
LYS28.NZ-ASP32.OD2 43.78
LYS28.NZ-ASP32.OD1 42.11
LYS28.NZ-ASP32.OD1 46.41
LYS347.NZ-ASP328.O 24.16
ASP32.N-LYS28.O 47.13
LYS347.NZ-ASP328.O 42.34
ASP223.OD2-ARG186.NH2 90.67
ARG186.NE-ASP223.OD1 96.89
ARG186.NE-ASP223.OD1 98.56
ARG186.NE-ASP223.OD1 97.61 ARG186.NH2-ASP223.OD2 98.80
ARG186.NH2-ASP223.OD2 99.04
ARG186.NH2-ASP223.OD2 99.76
ARG186.NH2-ASP223.OD2 99.28
LYS28.NZ-ASP101.OD1 12.20
LYS28.NZ-ASP101.OD1 14.83
LYS28.NZ-ASP101.OD2 16.51 ARG186.NE-ASP223.OD1 98.80
LYS28.NZ-ASP101.OD2 13.88
Rep5
LYS28.NZ-ASP101.OD1 18.18
LYS28.NZ-ASP101.OD1 11.00
Rep4
LYS28.NZ-ASP101.OD2 15.31
Rep2
Rep1
Rep3
Table 4.6 The HBs (with occupancy rates .≥10%) of SBs F:ASP101-F:LYS28, F:ASP223-F:ARG186, F:ASP328-F:LYS347, F:ASP32-F:LYS28, F:ASP369F:LYS394, F:ASP534-F:ARG560, F:GLU136-F:ARG21, F:GLU142-F:ARG409, F:GLU143-F:LYS146, F:GLU201-F:ARG178, F:GLU244-F:LYS276, F:GLU353-F:LYS347, F:GLU418-F:LYS430, F:GLU420-F:LYS430, F:GLU551-F:LYS477, F:GLU162-F:LYS524, F:ASP315-F:LYS345, and F:ASP315F:F:ARG332 within F chain (i.e., within NSP13.2) during the six replicates’ (each with 5 .μs) MD simulations
210 4 RNA Helicase
LYS276.NZ-GLU244.OE2 20.33
LYS276.NZ-GLU244.OE1 17.22
LYS347.NZ-GLU353.OE1 56.22
LYS347.NZ-GLU353.OE2 41.15
LYS430.NZ-GLU418.OE2 40.19
LYS430.NZ-GLU418.OE1 37.32
LYS430.NZ-GLU420.OE2 52.63
LYS430.NZ-GLU420.OE1 44.74
LYS477.NZ-GLU551.OE1 56.22
LYS477.NZ-GLU551.OE2 49.28
LYS524.NZ-GLU162.OE1 36.36
LYS524.NZ-GLU162.OE2 34.69
LYS345.NZ-ASP315.OD1 38.76
LYS345.NZ-ASP315.OD2 36.84
ARG332.NH2-ASP315.OD1 26.32
ARG332.NE-ASP315.OD2 23.68
ARG332.NE-ASP315.OD1 18.18
LYS276.NZ-GLU244.OE2 33.73
LYS276.NZ-GLU244.OE1 30.62
LYS347.NZ-GLU353.OE2 52.87
LYS347.NZ-GLU353.OE1 51.20
LYS430.NZ-GLU418.OE1 35.89
LYS430.NZ-GLU418.OE2 29.67
LYS430.NZ-GLU420.OE1 41.87
LYS430.NZ-GLU420.OE2 41.15
LYS477.NZ-GLU551.OE2 37.80
LYS477.NZ-GLU551.OE1 36.60
LYS524.NZ-GLU162.OE1 47.13
LYS524.NZ-GLU162.OE2 44.02
LYS345.NZ-ASP315.OD2 29.90
LYS345.NZ-ASP315.OD1 27.51
ARG332.NH2-ASP315.OD2 32.30
ARG332.NH2-ASP315.OD1 26.79
ARG332.NE-ASP315.OD1 16.51
ARG332.NH2-ASP315.OD2 17.94
LYS276.N-GLU244.O 22.49
LYS276.N-GLU244.O 37.32
ARG332.NE-ASP315.OD2 33.25
ARG332.NH2-ASP315.OD1 42.58
ARG332.NH2-ASP315.OD2 65.55
LYS524.NZ-GLU162.OE2 41.63
LYS524.NZ-GLU162.OE1 42.34
LYS477.NZ-GLU551.OE1 52.63
LYS477.NZ-GLU551.OE2 53.59
LYS430.NZ-GLU420.OE2 37.80
LYS430.NZ-GLU420.OE1 47.85
LYS430.NZ-GLU418.OE2 28.95
LYS430.NZ-GLU418.OE1 30.38
LYS347.NZ-GLU353.OE1 52.63
LYS347.NZ-GLU353.OE2 54.55
LYS276.NZ-GLU244.OE1 15.07
LYS276.NZ-GLU244.OE2 17.46
LYS276.N-GLU244.O 23.44
ARG332.NH1-ASP315.OD1 12.20
ARG332.NH1-ASP315.OD2 14.59
ARG332.NH2-ASP315.OD2 30.86
ARG332.NH2-ASP315.OD1 43.78
LYS345.NZ-ASP315.OD2 28.95 ARG332.NH2-ASP315.OD1 66.03
LYS345.NZ-ASP315.OD1 24.64
LYS524.NZ-GLU162.OE1 30.38
LYS345.NZ-ASP315.OD1 18.66
LYS524.NZ-GLU162.OE2 31.34
LYS477.NZ-GLU551.OE1 33.01
LYS477.NZ-GLU551.OE2 35.65
LYS430.NZ-GLU420.OE2 47.85
LYS430.NZ-GLU420.OE1 51.91
LYS430.NZ-GLU418.OE1 40.43
LYS430.NZ-GLU418.OE2 46.17
LYS347.NZ-GLU353.OE2 47.37
LYS347.NZ-GLU353.OE1 52.87
LYS276.NZ-GLU244.OE1 14.11
LYS276.NZ-GLU244.OE2 14.83
LYS276.N-GLU244.O 15.55
LYS524.NZ-GLU162.OE1 14.83
LYS524.NZ-GLU162.OE2 18.18
LYS477.NZ-GLU551.OE2 38.76
LYS477.NZ-GLU551.OE1 42.58
LYS430.NZ-GLU420.OE1 38.52
LYS430.NZ-GLU420.OE2 40.19
LYS430.NZ-GLU418.OE1 27.27
LYS430.NZ-GLU418.OE2 30.38
LYS347.NZ-GLU353.OE1 53.11
LYS347.NZ-GLU353.OE2 54.55
LYS276.NZ-GLU244.OE2 16.27
LYS276.NZ-GLU244.OE1 16.99
LYS276.N-GLU244.O 17.7
ARG332.NH1-ASP315.OD1 11.96
ARG332.NH2-ASP315.OD1 63.64
LYS345.NZ-ASP315.OD2 15.07
LYS345.NZ-ASP315.OD1 20.33
LYS477.NZ-GLU551.OE1 47.13
LYS477.NZ-GLU551.OE2 50.72
LYS430.NZ-GLU420.OE2 33.97
LYS430.NZ-GLU420.OE1 39.47
LYS430.NZ-GLU418.OE1 30.38
LYS430.NZ-GLU418.OE2 32.54
LYS347.NZ-GLU353.OE1 47.61
LYS347.NZ-GLU353.OE2 58.85
LYS276.NZ-GLU244.OE2 18.18
LYS276.N-GLU244.O 18.42
LYS276.NZ-GLU244.OE1 18.66
4.4 Concluding Remarks 211
212
4 RNA Helicase
Fig. 4.5 The SBs within E-chain (i.e., NSP13.1) during the six replicates’ MD simulations, where each replicate has 5 .μs MD
4.4 Concluding Remarks
Fig. 4.5 (continued)
213
214
4 RNA Helicase
Fig. 4.6 The SBs within F-chain (i.e., NSP13.2) during the six replicates’ MD simulations, where each replicate has 5 .μs MD
4.4 Concluding Remarks
Fig. 4.6 (continued)
215
216
Fig. 4.6 (continued)
4 RNA Helicase
4.4 Concluding Remarks
217
Fig. 4.7 The SBs within A-chain (i.e., NSP12) during the six replicates’ MD simulations, where each replicate has 5 .μs MD
218
Fig. 4.7 (continued)
4 RNA Helicase
4.4 Concluding Remarks
219
Fig. 4.8 The SBs linking A- and B-chains (i.e., NSP12, NSP8a) and within C-chain (i.e., NSP7) during the six replicates’ MD simulations, where each replicate has 5 .μs MD
220
4 RNA Helicase
Table 4.7 The SBs within E-chain NSP13.1 during the six replicates’ (each with 5 .μs) MD simulations Rep1
Rep2
Rep3
Rep4
Rep5
ASP101-LYS28
ASP101-LYS28
ASP101-LYS28
ASP101-LYS28
ASP101-LYS28
ASP101-LYS28
ASP160-ARG161
ASP160-ARG161
ASP160-ARG161
ASP113-LYS414
ASP160-ARG161
ASP160-ARG161
Rep6
ASP160-LYS218
ASP160-ARG212
ASP160-LYS218
ASP160-ARG161
ASP160-LYS218
ASP160-LYS218
ASP204-ARG490
ASP160-LYS218
ASP204-LYS524
ASP160-LYS218
ASP204-ARG490
ASP204-ARG161
ASP204-LYS524
ASP204-ARG161
ASP207-ARG155
ASP204-ARG490
ASP207-ARG155
ASP204-ARG490
ASP207-ARG155
ASP204-ARG490
ASP207-ARG173
ASP204-LYS524
ASP207-ARG173
ASP204-LYS524
ASP207-ARG173
ASP204-LYS524
ASP223-ARG186
ASP207-ARG155
ASP207-LYS202
ASP207-ARG155
ASP223-ARG186
ASP207-ARG155
ASP315-ARG332
ASP207-ARG173
ASP223-ARG186
ASP207-ARG173
ASP315-ARG332
ASP207-ARG173
ASP328-LYS329
ASP207-LYS202
ASP315-ARG332
ASP207-LYS202
ASP315-ARG339
ASP223-ARG186
ASP328-LYS347
ASP223-ARG186
ASP315-LYS345
ASP223-ARG186
ASP315-LYS345
ASP260-ARG442
ASP32-LYS28
ASP315-ARG332
ASP315-LYS508
ASP260-ARG442
ASP328-LYS329
ASP315-ARG332
ASP344-ARG332
ASP315-LYS345
ASP328-LYS329
ASP315-ARG332
ASP328-LYS347
ASP315-LYS345
ASP344-LYS345
ASP328-LYS329
ASP328-LYS347
ASP315-ARG339
ASP32-LYS28
ASP328-LYS329
ASP369-ARG303
ASP328-LYS347
ASP32-LYS28
ASP315-LYS345
ASP344-ARG332
ASP328-LYS345
ASP369-LYS394
ASP32-LYS28
ASP344-ARG332
ASP328-LYS329
ASP344-LYS345
ASP328-LYS347
ASP383-LYS139
ASP344-ARG332
ASP344-LYS345
ASP328-LYS347
ASP369-ARG303
ASP32-LYS28
ASP401-LYS430
ASP344-LYS345
ASP344-LYS508
ASP32-LYS28
ASP369-LYS394
ASP344-ARG332
ASP435-LYS271
ASP369-ARG303
ASP369-ARG303
ASP344-ARG332
ASP374-LYS288
ASP344-LYS345
ASP450-LYS460
ASP369-LYS394
ASP369-LYS394
ASP344-ARG339
ASP383-LYS139
ASP369-ARG303
ASP458-LYS460
ASP401-LYS430
ASP383-ARG409
ASP344-LYS345
ASP401-LYS430
ASP369-LYS394
ASP466-ARG442
ASP435-LYS271
ASP401-LYS430
ASP369-ARG303
ASP435-LYS271
ASP374-LYS320
ASP466-LYS465
ASP450-LYS460
ASP435-LYS271
ASP369-LYS394
ASP450-LYS460
ASP383-LYS139
ASP466-LYS467
ASP450-LYS462
ASP450-LYS460
ASP401-LYS430
ASP466-LYS465
ASP401-LYS430
ASP483-ARG490
ASP450-LYS465
ASP450-LYS462
ASP435-LYS271
ASP466-LYS467
ASP435-LYS271
ASP534-ARG560
ASP458-LYS584
ASP450-LYS465
ASP450-LYS460
ASP483-ARG490
ASP450-LYS460
ASP542-LYS508
ASP466-LYS465
ASP458-LYS584
ASP450-LYS462
ASP534-ARG560
ASP450-LYS462
ASP542-LYS569
ASP466-LYS467
ASP466-LYS462
ASP450-LYS465
ASP542-LYS508
ASP450-LYS465
ASP580-ARG579
ASP466-LYS473
ASP466-LYS465
ASP458-LYS584
ASP542-LYS569
ASP466-LYS465
ASP580-LYS584
ASP483-LYS202
ASP466-LYS467
ASP466-LYS462
ASP580-ARG579
ASP466-LYS467
ASP583-ARG579
ASP534-ARG560
ASP483-ARG490
ASP466-LYS465
ASP580-LYS584
ASP483-ARG490
ASP583-LYS584
ASP542-ARG507
ASP483-LYS202
ASP466-LYS467
ASP583-ARG579
ASP534-ARG560
ASP59-LYS40
ASP542-LYS508
ASP534-ARG560
ASP483-ARG173
ASP59-LYS40
ASP542-ARG507
GLU128-ARG129
ASP542-LYS569
ASP534-LYS414
ASP483-LYS202
GLU128-ARG129
ASP542-LYS508
GLU128-LYS131
ASP580-ARG579
ASP542-ARG507
ASP534-ARG560
GLU128-LYS131
ASP542-LYS569
GLU136-ARG21
ASP580-LYS584
ASP542-LYS508
ASP542-ARG443
GLU136-ARG21
ASP580-ARG579
GLU142-ARG409
ASP583-ARG579
ASP542-LYS569
ASP542-ARG507
GLU142-ARG409
ASP580-LYS584
GLU142-LYS139
ASP583-LYS584
ASP56-ARG22
ASP542-LYS508
GLU142-LYS139
ASP583-ARG579
GLU143-LYS139
ASP59-LYS40
ASP580-ARG579
ASP542-LYS569
GLU143-LYS139
ASP583-LYS584
GLU143-LYS146
ASP59-LYS73
ASP580-LYS584
ASP56-ARG22
GLU143-LYS146
ASP59-LYS40
GLU156-ARG155
GLU128-ARG129
ASP583-ARG579
ASP56-LYS73
GLU156-ARG155
GLU128-ARG129
GLU162-ARG161
GLU128-LYS131
ASP59-LYS40
ASP580-ARG579
GLU162-ARG161
GLU128-LYS131
GLU162-LYS524
GLU136-ARG15
GLU128-ARG129
ASP580-LYS584
GLU162-LYS524
GLU136-ARG21
GLU168-LYS171
GLU136-ARG21
GLU128-LYS131
ASP583-ARG579
GLU168-LYS171
GLU142-ARG409
GLU197-ARG337
GLU142-ARG409
GLU136-ARG21
ASP583-LYS584
GLU197-ARG337
GLU142-LYS139
GLU197-ARG339
GLU142-LYS139
GLU142-ARG409
ASP59-LYS40
GLU197-ARG339
GLU143-LYS139
GLU201-ARG178
GLU142-LYS146
GLU142-LYS139
ASP59-LYS73
GLU201-ARG161
GLU143-LYS146
GLU201-ARG212
GLU143-ARG21
GLU142-LYS146
GLU201-ARG178
GLU156-ARG155
GLU244-LYS276
GLU143-LYS139
GLU143-ARG21
GLU128-LYS131
GLU201-ARG212
GLU162-ARG161
GLU261-ARG442
GLU143-LYS146
GLU143-LYS139
GLU136-ARG15
GLU244-LYS276
GLU162-LYS524
GLU261-LYS465
GLU156-ARG155
GLU143-LYS146
GLU136-ARG21
GLU261-ARG442
GLU168-LYS171
GLU319-LYS320
GLU162-ARG161
GLU156-ARG155
GLU136-ARG22
GLU261-LYS465
GLU197-ARG337
GLU319-LYS323
GLU162-LYS524
GLU162-ARG161
GLU142-ARG409
GLU319-LYS323
GLU197-ARG339
GLU319-LYS345
GLU168-LYS171
GLU162-LYS524
GLU142-LYS139
GLU319-LYS345
GLU201-ARG178
GLU319-LYS569
GLU197-ARG337
GLU168-LYS171
GLU142-LYS146
GLU319-LYS569
GLU201-ARG212
GLU341-ARG178
GLU197-ARG339
GLU197-ARG337
GLU143-ARG21
GLU341-ARG178
GLU244-LYS276
GLU341-ARG212
GLU201-ARG178
GLU197-ARG339
GLU143-LYS139
GLU341-ARG212
GLU261-ARG442
GLU341-LYS345
GLU201-ARG212
GLU201-ARG178
GLU143-LYS146
GLU341-ARG339
GLU261-LYS323
GLU353-LYS329
GLU201-ARG339
GLU201-ARG212
GLU156-ARG155
GLU353-LYS347
GLU261-LYS467
GLU353-LYS347
GLU201-LYS524
GLU201-ARG339
GLU162-ARG161
GLU365-ARG392
GLU319-LYS323
GLU365-ARG390
GLU244-LYS276
GLU201-LYS524
GLU162-LYS524
GLU128-ARG427
(continued)
4.4 Concluding Remarks
221
Table 4.7 (continued) Rep1
Rep2
Rep3
Rep4
Rep5
Rep6
GLU375-LYS288
GLU319-LYS345
GLU365-ARG392
GLU261-ARG442
GLU244-LYS276
GLU168-LYS171
GLU418-LYS430
GLU319-LYS508
GLU418-LYS430
GLU261-ARG443
GLU261-ARG442
GLU197-ARG337
GLU420-ARG427
GLU319-LYS569
GLU420-ARG427
GLU261-LYS323
GLU261-LYS323
GLU197-ARG339
GLU420-LYS430
GLU341-ARG178
GLU420-LYS430
GLU319-LYS323
GLU319-LYS320
GLU201-ARG178
GLU447-LYS467
GLU341-ARG212
GLU447-LYS467
GLU319-LYS345
GLU319-LYS323
GLU201-ARG212
GLU498-ARG497
GLU341-ARG339
GLU498-ARG497
GLU319-LYS508
GLU319-LYS345
GLU201-ARG339
GLU498-ARG502
GLU353-LYS329
GLU498-ARG502
GLU319-LYS569
GLU319-LYS508
GLU201-LYS524
GLU540-ARG443
GLU353-LYS347
GLU540-ARG443
GLU341-ARG178
GLU319-LYS569
GLU244-LYS276
GLU540-ARG567
GLU365-ARG390
GLU540-ARG567
GLU341-ARG212
GLU341-ARG212
GLU261-ARG442
GLU540-LYS320
GLU365-ARG392
GLU540-LYS320
GLU341-ARG332
GLU341-ARG339
GLU261-ARG443
GLU540-LYS569
GLU375-LYS288
GLU540-LYS569
GLU341-ARG339
GLU353-LYS329
GLU261-LYS323
GLU551-ARG579
GLU418-LYS430
GLU551-LYS477
GLU341-LYS345
GLU353-LYS347
GLU319-LYS345
GLU551-LYS477
GLU420-ARG427
GLU341-LYS508
GLU365-ARG392
GLU319-LYS508
GLU420-LYS430
GLU353-LYS329
GLU375-ARG567
GLU319-LYS569
GLU447-LYS465
GLU353-LYS347
GLU418-LYS430
GLU341-ARG178
GLU447-LYS467
GLU365-ARG392
GLU420-ARG427
GLU341-ARG212
GLU447-LYS584
GLU375-ARG567
GLU420-LYS430
GLU341-ARG332
GLU498-ARG497
GLU418-LYS430
GLU447-LYS462
GLU341-ARG339
GLU498-ARG502
GLU420-ARG427
GLU447-LYS465
GLU341-LYS345
GLU540-ARG443
GLU420-LYS430
GLU447-LYS467
GLU341-LYS508
GLU540-ARG567
GLU447-LYS462
GLU498-ARG497
GLU353-LYS329
GLU540-LYS320
GLU447-LYS465
GLU498-ARG502
GLU353-LYS347
GLU551-LYS477
GLU447-LYS467
GLU540-ARG443
GLU365-ARG392
GLU498-ARG497
GLU540-LYS320
GLU375-ARG567
GLU498-ARG502
GLU540-LYS569
GLU418-LYS430
GLU540-ARG443
GLU551-ARG579
GLU420-ARG427
GLU540-LYS320
GLU551-LYS477
GLU420-LYS430
GLU540-LYS569
GLU447-LYS462
GLU551-ARG579
GLU447-LYS465
GLU551-LYS477
GLU447-LYS467 GLU498-ARG497 GLU498-ARG502 GLU540-ARG443 GLU540-LYS320 GLU540-LYS569 GLU551-LYS477
222
4 RNA Helicase
Table 4.8 The SBs within F-chain NSP13.2 during the six replicates’ (each with 5 .μs) MD simulations Rep1
Rep2
Rep3
Rep4
Rep5
ASP101-LYS28
ASP101-ARG129
ASP101-ARG129
ASP101-LYS28
ASP101-LYS28
ASP101-LYS28
ASP160-ARG161
ASP101-LYS28
ASP101-LYS28
ASP160-ARG161
ASP160-ARG161
ASP160-ARG161
Rep6
ASP160-LYS218
ASP160-ARG161
ASP160-ARG161
ASP160-ARG212
ASP160-ARG339
ASP160-ARG339
ASP204-ARG161
ASP160-ARG212
ASP160-LYS218
ASP160-ARG339
ASP160-LYS218
ASP160-LYS218
ASP204-ARG490
ASP160-LYS218
ASP204-ARG490
ASP160-LYS218
ASP204-ARG161
ASP204-ARG161
ASP204-LYS524
ASP204-ARG161
ASP204-LYS524
ASP204-ARG161
ASP204-ARG560
ASP204-ARG560
ASP207-ARG155
ASP204-ARG490
ASP207-ARG155
ASP204-LYS202
ASP204-LYS202
ASP204-LYS202
ASP207-ARG173
ASP204-LYS202
ASP207-ARG173
ASP204-LYS524
ASP207-ARG155
ASP207-ARG155
ASP207-LYS202
ASP204-LYS524
ASP207-LYS202
ASP207-ARG155
ASP207-ARG173
ASP207-ARG173
ASP223-ARG186
ASP207-ARG155
ASP223-ARG186
ASP207-ARG173
ASP207-ARG560
ASP207-LYS202
ASP315-ARG332
ASP207-ARG173
ASP260-ARG442
ASP207-LYS202
ASP207-LYS202
ASP223-ARG186
ASP315-LYS345
ASP207-LYS202
ASP260-LYS465
ASP223-ARG186
ASP223-ARG186
ASP260-LYS323
ASP328-LYS329
ASP207-LYS524
ASP315-ARG332
ASP315-ARG178
ASP260-ARG442
ASP315-ARG178
ASP328-LYS345
ASP223-ARG186
ASP315-ARG339
ASP315-ARG332
ASP260-ARG443
ASP315-ARG332
ASP328-LYS347
ASP260-ARG442
ASP315-LYS345
ASP328-LYS329
ASP315-ARG178
ASP315-LYS202
ASP32-LYS28
ASP315-ARG212
ASP328-LYS329
ASP328-LYS347
ASP315-ARG332
ASP328-LYS329
ASP344-ARG332
ASP315-ARG332
ASP328-LYS347
ASP32-LYS28
ASP328-LYS329
ASP328-LYS347
ASP344-LYS345
ASP315-LYS345
ASP32-LYS28
ASP32-LYS94
ASP328-LYS345
ASP32-LYS28
ASP369-ARG303
ASP328-LYS329
ASP344-ARG332
ASP344-LYS345
ASP328-LYS347
ASP344-LYS345
ASP369-LYS394
ASP328-LYS347
ASP344-LYS345
ASP369-LYS394
ASP32-LYS28
ASP369-ARG303
ASP374-LYS288
ASP32-LYS28
ASP369-ARG303
ASP383-LYS139
ASP344-ARG339
ASP369-LYS394
ASP383-ARG409
ASP344-ARG332
ASP369-LYS394
ASP401-LYS288
ASP344-LYS345
ASP383-LYS139
ASP383-LYS139
ASP344-LYS345
ASP374-LYS288
ASP435-LYS271
ASP369-ARG303
ASP401-LYS288
ASP401-LYS430
ASP369-LYS394
ASP435-LYS271
ASP450-LYS462
ASP369-LYS394
ASP435-LYS271
ASP401-LYS460
ASP374-LYS288
ASP450-LYS462
ASP450-LYS465
ASP374-LYS288
ASP450-LYS462
ASP435-LYS271
ASP435-LYS271
ASP466-LYS465
ASP458-LYS460
ASP401-LYS288
ASP458-LYS460
ASP450-LYS462
ASP450-LYS462
ASP466-LYS467
ASP458-LYS584
ASP435-LYS271
ASP458-LYS462
ASP458-LYS460
ASP458-LYS460
ASP483-ARG490
ASP466-LYS462
ASP450-LYS462
ASP458-LYS584
ASP466-LYS465
ASP458-LYS462
ASP483-LYS202
ASP466-LYS465
ASP458-LYS460
ASP466-LYS462
ASP466-LYS467
ASP466-ARG442
ASP534-ARG560
ASP466-LYS467
ASP458-LYS584
ASP466-LYS465
ASP483-ARG490
ASP466-LYS465
ASP542-LYS508
ASP483-ARG490
ASP466-LYS465
ASP466-LYS467
ASP483-LYS202
ASP466-LYS467
ASP542-LYS569
ASP483-LYS524
ASP466-LYS467
ASP483-ARG490
ASP534-ARG560
ASP483-ARG490
ASP580-ARG579
ASP534-ARG178
ASP483-ARG490
ASP483-LYS524
ASP542-ARG507
ASP483-LYS202
ASP580-LYS584
ASP534-ARG560
ASP483-LYS524
ASP534-ARG161
ASP542-LYS508
ASP534-ARG560
ASP583-ARG579
ASP542-LYS508
ASP534-ARG560
ASP534-ARG560
ASP542-LYS569
ASP542-LYS508
ASP583-LYS584
ASP542-LYS569
ASP534-LYS202
ASP534-ARG567
ASP580-ARG579
ASP542-LYS569
ASP59-LYS40
ASP580-ARG579
ASP542-ARG443
ASP542-ARG443
ASP580-LYS584
ASP580-ARG579
GLU128-ARG129
ASP580-LYS460
ASP542-LYS508
ASP542-LYS508
ASP583-ARG579
ASP580-LYS584
GLU128-LYS131
ASP580-LYS584
ASP542-LYS569
ASP542-LYS569
ASP583-LYS584
ASP583-ARG579
GLU136-ARG21
ASP583-ARG579
ASP578-LYS477
ASP580-ARG579
ASP59-LYS40
ASP59-LYS73
GLU142-ARG409
ASP583-LYS460
ASP580-ARG579
ASP580-LYS460
GLU128-ARG129
GLU128-ARG129
GLU142-LYS139
ASP583-LYS462
ASP580-LYS460
ASP580-LYS584
GLU128-LYS131
GLU128-LYS131
GLU142-LYS146
ASP59-LYS40
ASP580-LYS584
ASP583-ARG579
GLU136-ARG21
GLU136-ARG129
GLU143-LYS139
GLU128-ARG129
ASP583-ARG579
ASP583-LYS460
GLU142-ARG409
GLU136-ARG21
GLU143-LYS146
GLU128-LYS131
ASP583-LYS460
ASP583-LYS462
GLU142-LYS139
GLU142-ARG409
GLU156-ARG155
GLU136-ARG21
ASP59-LYS40
ASP59-LYS40
GLU142-LYS146
GLU142-LYS139
GLU162-ARG161
GLU142-ARG409
GLU128-ARG129
GLU143-LYS139
GLU143-LYS139
GLU162-LYS524
GLU142-LYS139
GLU128-LYS131
GLU128-LYS131
GLU143-LYS146
GLU143-LYS146
GLU168-LYS171
GLU142-LYS146
GLU136-ARG21
GLU136-ARG21
GLU156-ARG155
GLU156-ARG155
GLU197-ARG337
GLU143-LYS139
GLU142-ARG409
GLU142-ARG409
GLU162-ARG161
GLU162-ARG161
GLU197-ARG339
GLU143-LYS146
GLU142-LYS139
GLU142-LYS139
GLU162-LYS524
GLU162-LYS524
GLU201-ARG178
GLU156-ARG155
GLU143-LYS139
GLU143-LYS139
GLU168-LYS171
GLU168-LYS171
GLU201-ARG212
GLU162-ARG161
GLU143-LYS146
GLU143-LYS146
GLU197-ARG337
GLU197-ARG337
GLU244-LYS276
GLU162-LYS524
GLU156-ARG155
GLU156-ARG155
GLU197-ARG339
GLU197-ARG339
GLU261-ARG442
GLU168-LYS171
GLU162-ARG161
GLU162-ARG161
GLU201-ARG178
GLU201-ARG178
GLU261-LYS323
GLU197-ARG337
GLU168-LYS171
GLU162-ARG560
GLU201-ARG212
GLU201-ARG212
GLU261-LYS465
GLU201-ARG178
GLU197-ARG337
GLU168-LYS171
GLU244-LYS276
GLU244-LYS276
GLU319-LYS320
GLU201-ARG212
GLU201-ARG178
GLU197-ARG337
GLU261-LYS323
GLU244-LYS394
GLU319-LYS323
GLU244-LYS276
GLU201-ARG212
GLU197-ARG339
GLU261-LYS467
GLU261-ARG442
GLU319-LYS345
GLU261-ARG442
GLU244-LYS276
GLU201-ARG178
GLU319-LYS320
GLU261-ARG443
GLU319-LYS569
GLU261-ARG443
GLU261-ARG442
GLU201-ARG212
GLU319-LYS323
GLU261-LYS320
GLU341-ARG212
GLU261-LYS323
GLU261-ARG443
GLU201-ARG339
GLU128-ARG129
(continued)
4.4 Concluding Remarks
223
Table 4.8 (continued) Rep1
Rep2
Rep3
Rep4
Rep5
Rep6
GLU319-LYS345
GLU261-LYS323
GLU341-ARG339
GLU319-LYS320
GLU261-LYS320
GLU244-LYS276
GLU319-LYS569
GLU319-LYS320
GLU353-LYS329
GLU319-LYS323
GLU261-LYS323
GLU261-ARG442
GLU341-ARG332
GLU319-LYS323
GLU353-LYS347
GLU341-ARG161
GLU261-LYS508
GLU261-LYS323
GLU341-ARG337
GLU319-LYS345
GLU365-ARG390
GLU341-ARG178
GLU319-LYS320
GLU261-LYS508
GLU341-ARG339
GLU341-ARG332
GLU365-ARG392
GLU341-ARG212
GLU319-LYS323
GLU319-LYS320
GLU353-LYS329
GLU341-ARG337
GLU375-ARG567
GLU341-ARG339
GLU341-ARG161
GLU319-LYS323
GLU353-LYS347
GLU341-ARG339
GLU375-LYS288
GLU353-LYS329
GLU341-ARG178
GLU341-ARG161
GLU365-ARG390
GLU353-LYS329
GLU418-LYS430
GLU353-LYS347
GLU341-ARG212
GLU341-ARG178
GLU365-ARG392
GLU353-LYS347
GLU420-ARG427
GLU365-ARG390
GLU341-ARG332
GLU341-ARG212
GLU375-LYS288
GLU365-ARG390
GLU420-LYS430
GLU365-ARG392
GLU341-ARG337
GLU341-ARG339
GLU418-LYS430
GLU365-ARG392
GLU447-LYS467
GLU418-LYS430
GLU341-ARG339
GLU353-LYS329
GLU420-ARG427
GLU375-ARG567
GLU498-ARG497
GLU420-ARG427
GLU353-LYS329
GLU353-LYS347
GLU420-LYS430
GLU375-LYS288
GLU498-ARG502
GLU420-LYS430
GLU353-LYS347
GLU365-ARG390
GLU498-ARG497
GLU418-ARG560
GLU540-ARG443
GLU447-LYS462
GLU365-ARG390
GLU365-ARG392
GLU498-ARG502
GLU418-LYS430
GLU540-LYS569
GLU447-LYS465
GLU365-ARG392
GLU418-LYS430
GLU540-ARG443
GLU420-ARG427
GLU551-LYS477
GLU447-LYS467
GLU375-LYS288
GLU420-ARG427
GLU540-LYS569
GLU420-LYS430
GLU498-ARG497
GLU418-LYS430
GLU420-LYS430
GLU551-ARG579
GLU498-ARG497
GLU498-ARG502
GLU420-ARG427
GLU447-LYS462
GLU551-LYS477
GLU498-ARG502
GLU551-ARG579
GLU420-LYS430
GLU447-LYS465
GLU540-ARG443
GLU551-LYS477
GLU447-LYS462
GLU447-LYS467
GLU540-ARG567
GLU447-LYS465
GLU498-ARG497
GLU540-LYS320
GLU447-LYS467
GLU498-ARG502
GLU540-LYS569
GLU498-ARG497
GLU551-LYS477
GLU551-LYS477
GLU498-ARG502 GLU540-ARG567 GLU540-LYS569 GLU551-ARG579 GLU551-LYS477
224
4 RNA Helicase
Table 4.9 The SBs within A-chain NSP12 during the six replicates’ (each with 5 .μs) MD simulations Rep1
Rep2
Rep3
Rep4
Rep5
Rep6
ASP100-ARG10
ASP100-ARG10
ASP100-ARG10
ASP100-ARG10
ASP100-ARG10
ASP100-ARG10
ASP107-ARG74
ASP126-ARG33
ASP107-ARG74
ASP100-LYS98
ASP107-ARG74
ASP107-ARG74
ASP126-ARG33
ASP135-LYS47
ASP126-ARG33
ASP107-ARG74
ASP109-ARG74
ASP109-ARG74
ASP126-LYS47
ASP135-LYS780
ASP126-LYS47
ASP126-ARG33
ASP126-ARG33
ASP126-ARG33
ASP135-LYS47
ASP135-LYS783
ASP135-LYS47
ASP135-LYS780
ASP135-LYS47
ASP135-LYS47
ASP135-LYS780
ASP140-LYS143
ASP135-LYS780
ASP135-LYS783
ASP135-LYS780
ASP135-LYS780
ASP135-LYS783
ASP153-ARG173
ASP135-LYS783
ASP140-LYS143
ASP135-LYS783
ASP135-LYS783
ASP140-LYS143
ASP155-LYS159
ASP140-LYS143
ASP153-ARG173
ASP140-LYS143
ASP140-LYS143
ASP140-LYS47
ASP161-LYS159
ASP140-LYS47
ASP154-LYS143
ASP140-LYS160
ASP140-LYS160
ASP153-ARG173
ASP161-LYS160
ASP153-ARG173
ASP161-LYS159
ASP153-ARG173
ASP153-ARG173
ASP153-LYS159
ASP164-LYS159
ASP154-LYS143
ASP161-LYS160
ASP153-LYS159
ASP154-LYS143
ASP154-LYS143
ASP170-ARG173
ASP155-LYS159
ASP164-LYS159
ASP154-ARG173
ASP161-LYS159
ASP155-LYS159
ASP170-LYS159
ASP161-LYS159
ASP170-ARG173
ASP154-LYS159
ASP161-LYS160
ASP161-LYS159
ASP194-ARG197
ASP161-LYS160
ASP170-LYS159
ASP155-ARG173
ASP164-LYS159
ASP161-LYS160
ASP194-LYS288
ASP170-ARG173
ASP194-ARG197
ASP155-LYS159
ASP170-ARG173
ASP170-ARG173
ASP218-ARG116
ASP194-ARG197
ASP194-LYS288
ASP161-LYS159
ASP194-ARG197
ASP170-LYS159
ASP218-LYS73
ASP194-LYS288
ASP208-ARG33
ASP161-LYS160
ASP194-LYS288
ASP194-ARG197
ASP235-ARG467
ASP218-ARG116
ASP218-ARG116
ASP164-LYS159
ASP208-ARG33
ASP194-LYS288
ASP235-ARG733
ASP218-LYS73
ASP235-ARG467
ASP170-ARG173
ASP218-ARG116
ASP218-ARG116
ASP235-ARG735
ASP235-ARG467
ASP235-ARG733
ASP170-LYS159
ASP218-LYS50
ASP218-LYS73
ASP258-LYS263
ASP235-ARG733
ASP235-ARG735
ASP194-ARG197
ASP235-ARG467
ASP235-ARG467
ASP260-LYS263
ASP235-ARG735
ASP258-ARG183
ASP194-LYS288
ASP235-ARG733
ASP235-ARG733
ASP269-LYS267
ASP258-LYS263
ASP258-ARG285
ASP208-ARG33
ASP235-ARG735
ASP235-ARG735
ASP269-LYS272
ASP260-LYS263
ASP258-LYS263
ASP218-ARG116
ASP258-LYS263
ASP258-LYS263
ASP274-LYS272
ASP269-LYS267
ASP258-LYS267
ASP235-ARG467
ASP260-LYS263
ASP260-LYS263
ASP284-LYS281
ASP269-LYS272
ASP258-LYS281
ASP235-ARG733
ASP269-LYS267
ASP269-LYS267
ASP284-LYS288
ASP274-LYS272
ASP260-ARG249
ASP258-LYS263
ASP269-LYS272
ASP269-LYS272
ASP291-ARG467
ASP284-LYS281
ASP260-LYS263
ASP260-ARG173
ASP274-LYS272
ASP274-LYS272
ASP291-ARG735
ASP284-LYS288
ASP260-LYS267
ASP260-LYS263
ASP284-LYS281
ASP284-LYS281
ASP29-ARG55
ASP291-ARG467
ASP260-LYS272
ASP269-LYS267
ASP284-LYS288
ASP284-LYS288
ASP303-ARG305
ASP291-ARG735
ASP260-LYS281
ASP269-LYS272
ASP291-ARG467
ASP291-ARG467
ASP303-ARG651
ASP29-ARG55
ASP269-LYS267
ASP274-LYS272
ASP291-ARG733
ASP291-ARG735
ASP304-ARG640
ASP303-ARG305
ASP269-LYS272
ASP284-LYS281
ASP291-ARG735
ASP29-ARG55
ASP304-ARG651
ASP304-ARG640
ASP274-LYS263
ASP284-LYS288
ASP303-ARG305
ASP29-LYS121
ASP336-ARG365
ASP304-ARG651
ASP274-LYS272
ASP291-ARG467
ASP303-ARG651
ASP303-ARG305
ASP358-ARG533
ASP336-ARG365
ASP284-ARG285
ASP291-ARG735
ASP304-ARG640
ASP304-ARG640
ASP390-ARG392
ASP358-ARG533
ASP284-LYS281
ASP29-ARG55
ASP304-ARG651
ASP304-ARG651
ASP3-ARG105
ASP36-ARG733
ASP284-LYS288
ASP29-ARG74
ASP336-ARG365
ASP336-ARG365
ASP3-ARG18
ASP390-ARG392
ASP291-ARG467
ASP303-ARG305
ASP358-ARG533
ASP358-ARG533
ASP40-ARG721
ASP3-ARG105
ASP291-ARG735
ASP304-ARG640
ASP390-ARG392
ASP36-ARG733
ASP40-LYS41
ASP40-ARG721
ASP303-ARG305
ASP336-ARG365
ASP3-ARG105
ASP390-ARG392
ASP40-LYS718
ASP40-LYS41
ASP303-ARG651
ASP358-ARG331
ASP3-ARG10
ASP3-ARG105
ASP418-LYS417
ASP40-LYS718
ASP304-ARG305
ASP358-ARG533
ASP40-ARG721
ASP3-ARG18
ASP418-LYS890
ASP418-LYS890
ASP304-ARG640
ASP390-ARG392
ASP40-LYS41
ASP40-ARG721
ASP421-LYS417
ASP421-LYS417
ASP304-ARG651
ASP3-ARG105
ASP40-LYS718
ASP40-LYS41
ASP452-ARG553
ASP445-ARG553
ASP336-ARG365
ASP3-ARG10
ASP421-LYS417
ASP40-LYS718
ASP452-ARG624
ASP452-ARG553
ASP358-ARG533
ASP3-ARG18
ASP452-ARG553
ASP418-LYS417
ASP452-LYS551
ASP452-ARG624
ASP36-ARG733
ASP40-ARG721
ASP452-ARG624
ASP418-LYS890
ASP454-ARG457
ASP454-ARG457
ASP390-ARG392
ASP40-LYS41
ASP452-LYS621
ASP421-LYS417
ASP465-ARG132
ASP465-ARG132
ASP3-ARG105
ASP40-LYS718
ASP454-ARG457
ASP445-ARG553
ASP477-ARG640
ASP477-ARG640
ASP3-ARG10
ASP421-LYS417
ASP465-ARG132
ASP452-ARG553
ASP477-LYS478
ASP477-LYS478
ASP3-ARG18
ASP452-ARG624
ASP477-ARG640
ASP452-ARG624
ASP481-LYS478
ASP481-LYS478
ASP3-LYS103
ASP452-LYS621
ASP477-LYS478
ASP454-ARG457
ASP481-LYS641
ASP481-LYS641
ASP3-LYS59
ASP454-ARG457
ASP477-LYS641
ASP465-ARG132
ASP484-LYS574
ASP484-LYS574
ASP40-ARG721
ASP465-ARG132
ASP481-LYS478
ASP477-ARG640
ASP499-ARG513
ASP499-ARG513
ASP40-LYS41
ASP477-ARG640
ASP481-LYS641
ASP477-LYS478
ASP499-LYS511
ASP499-LYS511
ASP40-LYS718
ASP477-LYS478
ASP484-LYS574
ASP481-LYS478
ASP523-LYS369
ASP523-LYS369
ASP418-LYS890
ASP477-LYS641
ASP499-ARG513
ASP484-LYS574
ASP608-ARG750
ASP608-ARG750
ASP421-LYS417
ASP481-LYS478
ASP499-LYS511
ASP499-ARG513
ASP608-LYS751
ASP608-LYS751
ASP452-ARG624
ASP481-LYS641
ASP523-LYS369
ASP499-LYS511
ASP60-ARG18
ASP60-ARG18
ASP452-LYS621
ASP484-LYS574
ASP608-ARG750
ASP517-ARG513
ASP618-LYS621
ASP618-LYS621
ASP454-ARG457
ASP499-ARG513
ASP608-LYS751
ASP523-LYS369
ASP618-LYS798
ASP618-LYS798
ASP465-ARG132
ASP499-LYS511
ASP60-ARG18
ASP608-ARG750
ASP623-ARG553
ASP623-ARG553
ASP477-ARG640
ASP517-ARG513
ASP618-ARG553
ASP608-LYS751
ASP623-ARG624
ASP623-ARG555
ASP477-LYS478
ASP523-LYS369
ASP618-LYS551
ASP60-ARG18
ASP623-LYS551
ASP623-LYS551
ASP477-LYS641
ASP608-ARG750
ASP618-LYS798
(continued)
4.4 Concluding Remarks
225
Table 4.9 (continued) Rep1
Rep2
Rep3
Rep4
Rep5
Rep6
ASP618-LYS798
ASP623-LYS621
ASP623-LYS621
ASP481-LYS478
ASP608-LYS751
ASP623-ARG624
ASP623-ARG553
ASP62-ARG18
ASP63-ARG18
ASP481-LYS641
ASP60-ARG18
ASP623-LYS621
ASP623-ARG555
ASP62-LYS59
ASP63-LYS59
ASP484-LYS574
ASP618-ARG553
ASP63-LYS59
ASP623-ARG624
ASP63-ARG18
ASP67-LYS121
ASP499-ARG513
ASP618-LYS551
ASP67-LYS121
ASP63-ARG18
ASP63-LYS59
ASP711-LYS41
ASP499-LYS511
ASP618-LYS798
ASP711-LYS47
ASP63-LYS59
ASP67-LYS121
ASP711-LYS714
ASP523-LYS369
ASP623-ARG624
ASP711-LYS714
ASP67-LYS121
ASP711-LYS714
ASP736-ARG305
ASP608-ARG750
ASP623-LYS621
ASP711-LYS780
ASP684-ARG631
ASP736-ARG305
ASP736-ARG735
ASP608-LYS603
ASP63-ARG18
ASP717-LYS714
ASP711-LYS714
ASP736-ARG735
ASP738-ARG726
ASP608-LYS751
ASP63-LYS59
ASP736-ARG305
ASP711-LYS780
ASP738-ARG726
ASP740-ARG726
ASP618-ARG553
ASP67-LYS121
ASP736-ARG735
ASP717-LYS718
ASP760-LYS621
ASP760-LYS621
ASP618-LYS551
ASP711-LYS47
ASP760-ARG553
ASP736-ARG305
ASP761-LYS621
ASP761-LYS621
ASP618-LYS798
ASP711-LYS714
ASP760-LYS551
ASP736-ARG735
ASP804-LYS807
ASP804-LYS807
ASP623-ARG624
ASP711-LYS780
ASP761-LYS551
ASP760-LYS621
ASP824-LYS821
ASP824-LYS821
ASP623-LYS621
ASP717-LYS714
ASP804-LYS807
ASP761-LYS621
ASP825-LYS603
ASP825-LYS603
ASP63-ARG18
ASP736-ARG305
ASP824-LYS821
ASP804-LYS807
ASP833-ARG836
ASP833-ARG836
ASP63-LYS59
ASP736-ARG735
ASP833-ARG836
ASP824-LYS821
ASP833-LYS438
ASP833-LYS438
ASP67-LYS121
ASP761-LYS551
ASP833-LYS438
ASP825-LYS603
ASP845-LYS849
ASP845-LYS849
ASP684-ARG569
ASP804-LYS807
ASP845-LYS411
ASP833-ARG836
ASP846-LYS849
ASP846-LYS849
ASP711-LYS47
ASP824-LYS821
ASP845-LYS545
ASP833-LYS438
ASP865-LYS593
ASP865-ARG836
ASP711-LYS714
ASP825-LYS603
ASP845-LYS849
ASP845-LYS411
ASP879-LYS426
ASP865-LYS593
ASP711-LYS780
ASP833-ARG836
ASP846-LYS411
ASP845-LYS849
ASP893-ARG889
ASP879-LYS426
ASP717-LYS714
ASP833-LYS438
ASP846-LYS849
ASP846-LYS411
ASP893-LYS890
ASP893-ARG889
ASP736-ARG305
ASP845-LYS411
ASP865-ARG836
ASP846-LYS849
ASP910-ARG914
ASP893-LYS890
ASP736-ARG735
ASP845-LYS545
ASP865-ARG858
ASP865-ARG836
ASP92-LYS91
ASP910-ARG889
ASP738-ARG305
ASP845-LYS849
ASP865-LYS593
ASP865-LYS593
ASP92-LYS98
ASP910-ARG914
ASP760-ARG553
ASP846-LYS411
ASP879-LYS426
ASP879-LYS426
GLU136-LYS160
ASP92-LYS91
ASP760-LYS551
ASP846-LYS849
ASP893-ARG889
ASP893-ARG889
GLU136-LYS780
GLU136-LYS160
ASP761-ARG553
ASP865-LYS593
ASP910-ARG889
ASP893-LYS890
GLU136-LYS783
GLU136-LYS780
ASP761-LYS551
ASP893-ARG889
ASP910-ARG914
ASP92-LYS91
GLU144-LYS121
GLU136-LYS783
ASP804-LYS807
ASP893-LYS890
ASP92-LYS91
GLU136-LYS160
GLU167-LYS159
GLU144-LYS121
ASP824-LYS821
ASP910-ARG889
GLU136-LYS160
GLU136-LYS780
GLU167-LYS160
GLU144-LYS143
ASP833-ARG836
ASP910-ARG914
GLU136-LYS47
GLU136-LYS783
GLU180-ARG183
GLU167-LYS159
ASP833-LYS438
ASP92-LYS91
GLU136-LYS780
GLU144-LYS121
GLU254-ARG183
GLU167-LYS160
ASP845-LYS849
GLU136-LYS160
GLU136-LYS783
226
4 RNA Helicase
Table 4.10 The SBs within A-chain NSP12 during the six replicates’ (each with 5 .μs) MD simulations (continuation) Rep1
Rep2
Rep3
Rep4
Rep5
GLU167-LYS159
GLU254-ARG285
GLU180-ARG183
ASP846-LYS411
GLU136-LYS47
GLU144-LYS121
GLU167-LYS160
GLU277-LYS272
GLU254-ARG183
ASP846-LYS849
GLU136-LYS780
GLU167-ARG457
Rep6
GLU180-ARG183
GLU277-LYS281
GLU254-ARG285
ASP865-ARG836
GLU136-LYS783
GLU167-LYS159
GLU254-ARG183
GLU278-LYS272
GLU277-LYS281
ASP865-LYS593
GLU144-LYS121
GLU180-ARG183
GLU254-ARG285
GLU278-LYS281
GLU278-LYS272
ASP879-LYS426
GLU144-LYS143
GLU254-ARG183
GLU277-LYS272
GLU350-ARG349
GLU278-LYS281
ASP893-ARG889
GLU167-ARG457
GLU254-ARG285
GLU277-LYS281
GLU370-ARG365
GLU350-ARG349
ASP893-LYS890
GLU167-LYS159
GLU277-LYS281
GLU278-LYS272
GLU370-LYS369
GLU370-ARG365
ASP910-ARG889
GLU180-ARG183
GLU278-LYS272
GLU278-LYS281
GLU431-LYS430
GLU370-LYS369
ASP910-ARG914
GLU254-ARG183
GLU278-LYS281
GLU350-ARG349
GLU436-LYS438
GLU431-LYS430
ASP92-LYS91
GLU254-ARG285
GLU350-ARG349
GLU370-ARG365
GLU474-ARG305
GLU436-LYS438
GLU136-LYS160
GLU277-LYS281
GLU370-LYS369
GLU370-LYS369
GLU474-ARG640
GLU474-ARG305
GLU136-LYS780
GLU278-LYS272
GLU431-LYS430
GLU431-LYS430
GLU522-LYS369
GLU474-ARG640
GLU136-LYS783
GLU278-LYS281
GLU436-LYS438
GLU436-LYS438
GLU58-ARG118
GLU58-ARG118
GLU144-LYS121
GLU350-ARG349
GLU474-ARG305
GLU474-ARG305
GLU610-LYS751
GLU610-LYS751
GLU144-LYS143
GLU370-ARG365
GLU474-ARG640
GLU474-ARG640
GLU61-ARG18
GLU61-ARG18
GLU167-ARG457
GLU370-LYS369
GLU58-ARG118
GLU522-LYS369
GLU658-ARG631
GLU658-ARG631
GLU167-LYS159
GLU431-LYS430
GLU58-ARG18
GLU58-ARG118
GLU658-ARG654
GLU658-ARG654
GLU167-LYS160
GLU436-LYS438
GLU610-LYS751
GLU58-ARG18
GLU665-LYS676
GLU665-LYS676
GLU180-ARG181
GLU474-ARG305
GLU61-ARG18
GLU610-LYS751
GLU729-ARG726
GLU729-ARG726
GLU180-ARG183
GLU474-ARG640
GLU61-LYS59
GLU61-ARG18
GLU729-ARG733
GLU729-ARG733
GLU254-ARG183
GLU522-LYS369
GLU658-ARG631
GLU658-ARG631
GLU744-ARG726
GLU729-LYS41
GLU254-ARG285
GLU58-ARG118
GLU665-LYS676
GLU658-ARG654
GLU796-LYS780
GLU744-ARG726
GLU254-LYS267
GLU58-ARG18
GLU729-ARG733
GLU665-LYS676
GLU796-LYS783
GLU796-LYS780
GLU277-LYS263
GLU610-LYS751
GLU744-ARG726
GLU729-ARG733
GLU802-LYS807
GLU796-LYS783
GLU277-LYS272
GLU61-ARG18
GLU796-LYS780
GLU744-ARG726
GLU811-ARG836
GLU802-LYS807
GLU277-LYS281
GLU658-ARG631
GLU796-LYS783
GLU796-LYS780
GLU811-LYS798
GLU811-ARG836
GLU278-LYS263
GLU658-ARG654
GLU802-LYS807
GLU796-LYS783
GLU83-LYS73
GLU811-LYS798
GLU278-LYS267
GLU665-LYS676
GLU811-ARG836
GLU802-LYS807
GLU876-LYS430
GLU83-LYS73
GLU278-LYS272
GLU729-ARG733
GLU811-LYS438
GLU811-LYS798
GLU894-LYS890
GLU876-LYS430
GLU278-LYS281
GLU744-ARG726
GLU811-LYS551
GLU811-LYS807
GLU917-ARG914
GLU894-LYS890
GLU350-ARG349
GLU796-LYS780
GLU811-LYS798
GLU83-LYS73
GLU919-ARG914
GLU917-ARG889
GLU370-LYS369
GLU796-LYS783
GLU83-ARG116
GLU857-ARG858
GLU922-LYS871
GLU917-ARG914
GLU431-LYS430
GLU802-LYS807
GLU83-LYS73
GLU876-LYS430
GLU919-ARG914
GLU436-LYS438
GLU811-ARG836
GLU857-ARG914
GLU894-LYS890
GLU922-LYS871
GLU474-ARG305
GLU811-LYS438
GLU894-LYS890
GLU917-ARG914
GLU474-ARG640
GLU811-LYS551
GLU917-ARG889
GLU919-ARG914
GLU58-ARG118
GLU811-LYS798
GLU917-ARG914
GLU922-LYS871
GLU58-ARG18
GLU83-ARG116
GLU919-ARG914
GLU610-LYS751
GLU83-LYS73
GLU922-LYS871
GLU61-ARG18
GLU857-ARG914
GLU658-ARG631
GLU876-LYS807
GLU658-ARG654
GLU894-LYS890
GLU665-LYS676
GLU917-ARG914
GLU729-ARG733
GLU919-ARG914
GLU744-ARG726
GLU922-LYS871
GLU796-LYS780 GLU796-LYS783 GLU802-LYS807 GLU811-ARG836 GLU811-LYS438 GLU811-LYS551 GLU83-ARG116 GLU83-LYS73 GLU876-LYS430 GLU876-LYS807 GLU894-LYS890 GLU917-ARG914 GLU919-ARG914 GLU922-LYS871
Chapter 5
RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA, ADP-Mg2+ , and ATP-Mg2+
.
.
Abstract Firstly, we optimized the molecular structure of the NSP13-bound SARS-CoV-2 replication-transcription complex (RTC, starting from the NSP13.1open conformation with three cytosines (chain P and residues 36, 37, and 38) manually built onto the 3’ end of chain P, extending the product RNA into the NTP-entry channel of NSP12 to mimic the backtracked state of NSP12). We got some basic structural bioinformatics about the NSP13-bound SARS-CoV-2 replication-transcription complex and then confirmed these basic bioinformatics by analysis of an openly online accessible 500 .μs MD simulation trajectory. Interesting backtracking performance can be observed. Keywords COVID-19 virus · RNA helicase (NSP13) · Binding with RdRp, NSP7, NSP8a, NSP8b - pRNA, tRNA, ADP-Mg.2+ , ATP-Mg.2+ · Optimization and MD (molecular dynamics) studies · Basic structural bioinformatics
5.1 Introduction The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 genome is replicated and transcribed by its RNA-dependent RNA polymerase (RdRp), which is the target for antivirals such as remdesivir. In [225], the authors used a combination of approaches to show that backtracking (backward motion of the RdRp on the template RNA) is a feature of SARS-CoV-2 replication/transcription and concluded that backtracking may play a critical role in proofreading, a crucial process for SARS-CoV-2 resistance against many antivirals. The SARS-CoV-2 nonstructural proteins coordinate genome 26 replication and gene expression. Structural analyses revealed the basis for coupling of the essential NSP13 helicase with the RNA-dependent RNA polymerase (RdRp) where the holo-RdRp and RNA substrate (the replication-transcription complex, or RTC) are associated with two copies of NSP13 (NSP13.2 -RTC). One copy of NSP13 interacts with the template RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backward on the RNA template (backtracking), © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_5
227
228
5 RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA,. . .
prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of NSP13. The results of [66] suggest a mechanism for the NSP13.2 -RTC to turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis and backtracking in response to stimuli at the RdRp active site. In this chapter, we will study the NSP13 in complex with [RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA, ADP-Mg.2+ , ATP-Mg.2+ ] from optimization and MD point of view.
5.2 Materials and Methods A 500-.μs trajectory featuring nsp13-bound SARS-CoV-2 replication-transcription complex, starting from the NSP13.1-open conformation with three cytosines (chain P and residues 36, 37, and 38), is manually built onto the 3’ end of chain P, extending the product RNA into the NTP-entry channel of NSP12 to mimic the backtracked state of NSP12. In the MD simulation of data of DESRES-ANTON-13795965 of [321], both copies of NSP13 reoriented themselves while remaining bound to NSP12 [321]. For 500-.μs MD trajectories [321], we select 522 frames. In this chapter, firstly we optimized the structures of the NSP13-bound SARS-CoV-2 RTC and got some basic structural bioinformatics about the NSP13-bound SARS-CoV-2 replicationtranscription complex and then confirmed these basic bioinformatics by analysis of the 500 .μs MD simulation trajectories.
5.3 New Results and Discussions The optimized model studied in this chapter can be seen in Fig. 5.1a.
Fig. 5.1 (a) The 3D structure of the optimized NSP12-NSP8-NSP7-NSP13-tpRNA model (where A-chain is NSP12, B-chain is NSP8a, D-chain is NSP8b, C-chain is NSP7, EF-chains are NSP13, and P- and T-chains are p-RNA and t-RNA, respectively). (b, c, d) The ligands ADP2003, ATP1003, and ATP1003 interact with A-, E-, and F-chains, respectively
In Fig. 5.1b, the ligand ADP2003-MG2002 binds with A-chain (NSP12) residues PHE35, LYS50, ASN52, CYS53, LYS73, ARG74, HIS75, GLU83, ARG116, ASP208, ASN209, TYR217, ASP218, PHE219, and GLY220; in Fig. 5.1c, the
5.3 New Results and Discussions
229
ligand ATP1003-MG1004 binds with NSP13 E-chain residues GLU261, SER264, PRO283, PRO284, GLY285, THR286, GLY287, LYS288, SER289, HIS290, LYS320, LYS323, GLU375, GLN404, ARG442, ARG443, HIS464, GLY538, GLU540, THR566, ARG567, and LYS569; and in Fig. 5.1d, the ligand ATP1003MG1004 binds with NSP13 F-chain residues GLU261, PHE262, ASN265, PRO284, GLY285, THR286, GLY287, LYS288, SER289, HIS290, LYS320, ASP374, GLU375, GLN404, ARG442, ARG443, GLU540, ARG567, and LYS569.
Fig. 5.2 The optimized NSP12-NSP8-NSP7-NSP13-tpRNA model binding with ZN2000ZN2001, ZN1000-ZN1001-ZN1002, and ZN1000-ZN1001-ZN1002 for A (NSP12), E (NSP13), and F (NSP13) chains, respectively
In Fig. 5.2, the ZN2000-ZN2001 bind with A-chain (NSP12) residues HIS295, CYM301, LEU302, CYM306, ILE307, HIS309, CYM310; GLY486, CYM487, LYS532, HIS642, CYM645, and CYM646; the ZN1000-ZN1001-ZN1002 bind with NSP13 E-chain residues CYM5, LEU7, CYM8, ASN9, SER10, CYM26, CYM29; CYM50, ALA52, CYM55, VAL57, CYM72, HIS75; CYM16, CYM19, HIS33, HIS39, and ALA110; and the ZN1000-ZN1001-ZN1002 bind with NSP13 F-chain residues CYM5, LEU7, CYM8, ASN9, SER10, CYM26, CYM29, GLY99; CYM50, ALA52, CYM55, CYM72, HIS75; CYM16, CYM19, HIS33, HIS39, and ALA110. Table 5.1 and Fig. 5.3 show us the ABCDEF-chains’ residues of optimized NSP12-NSP8-NSP7-NSP13-tpRNA, binding with pRNA and tRNA. Table 5.2 lists the SBs in ABCDEF-chains of the optimized NSP12-NSP8-NSP7NSP13-tpRNA model. Among the SBs listed in Table 5.2, there are nine stronger SBs (with stronger HBs) among the A-B-C-D-E-F-chains during the 500 .μs MD; we list them in Table 5.3 and show them in Fig. 5.5. Within each chain of the NSP12-NSP8-NSP7-NSP13-tpRNA model, we also get some stronger SBs (with stronger HBs), which are listed in Tables 5.4 and 5.5. During the 500 .μs MD, the NSP12-NSP8-NSP7-NSP13-tpRNA model has some strong HBs listed in Table 5.6 to refer.
230
5 RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA,. . .
Table 5.1 The ABCDEF-chains’ residues of optimized NSP12-NSP8-NSP7-NSP13-tpRNA, binding with pRNA and tRNA tRNA
A408, A409, A410, A411, A495, A496, A497, A500, A501, A502, A503, A507, A508, A509, A511, A541, A543, A544, A545, A546, A547, A557, A558, A559, A560, A565, A569, A573, A576, A577, A580, A583, A589, A590, A591, A592, A594, A593, A595, A682, A683, A684, A685, A686, A687, A689, A849, A857, A864, A911, A914, A915, A920, A924; B39, B40, B43, B44, B46, B47, B57, B58, B61, B82; C21; D39, D40, D43, D44, D61, D62, D65, D69, D80; E15, E139, E142, E143, E147, E174, E175, E176, E177, E178, E179, E180, E230, E231, E232, E233, E234, E309, E310, E311, E335, E336, E337, E338, E339, E340, E359, E360, E361, E382, E408, E410, E516, E532, E534, E535
pRNA
A438, A439, A497, A513, A545, A548, A549, A550, A551, A553, A555, A593, A594, A619, A620, A621, A688, A758, A759, A760, A761, A798, A811, A813, A814, A815, A832, A836, A837, A840, A845, A849, A855, A857, A858, A861, A862, A865; B33, B36, B37, B46, B50, B51, B54, B57, B65, B72, B75; D33, D36, D46, D47, D50, D51, D54, D57, D58;
ptRNA p
A438, A439, A513, A548, A549, A550, A551, A553, A555, A563, A593, A619, A621, A688, A758, A759, A760, A761, A798, A811, A813, A814, A815, A832, A836, A837, A840, A845, A849, A855, A858, A861, A862, A865; B33, B36, B37, B50, B51, B54, B65, B72, B75; D33, D36, D46, D47, D50, D51, D54, D57, D58;
t
A408, A409, A410, A411, A495, A496, A497, A500, A501, A502, A503, A507, A508, A509, A511, A543, A544, A545, A546, A547, A558, A559, A565, A567, A569, A573, A576, A577, A580, A583, A589, A590, A591, A592, A594, A595, A560, A682, A684, A685, A686, A687, A689, A857, A864, A920, A924; B39, B40, B43, B44, B46, B47, B57, B58, B61, B82; C21; D39, D40, D43, D44, D61, D62, D65, D69, D80; E15, E139, E142, E143, E147, E174, E175, E176, E177, E178, E179, E180, E230, E231, E232, E233, E234, E309, E310, E311, E335, E336, E337, E338, E339, E340, E338, E359, E360, E361, E382, E408, E410, E516, E532, E534, E535
During the 500 .μs MD of the NSP12-NSP8-NSP7-NSP13-tpRNA model, we also find the changes of .α-helices as follows: in A-chain, for ASP154-ASN158 its .αhelix unfolds into turn and G-3-10-helix, for MET242-THR248 its .α-helix unfolds into G-3-10-helix and turn during frames 284–525, for ASN447-ASP454 its .α-helix unfolds into turn during frames 144–525, for GLY597-ASN600 its .α-helix unfolds into C-T-E during frames 354–525, for SER768-GLN773 its .α-helix unfolds into TE-G during frames 424–525; within B-chain, for LEU169-SER173 its G-3-10-helix changes into .α-helix and turn during frames 95–525; within D-chain, for LEU169SER173 its .α-helix unfolds during frames 25–484; within E-chain, for ALA446VAL456 its .α-helix is not stable and for VAL533-GLN537 its .α-helix is also not stable; and within F-chain, for ASN516-ILE525 its .α-helix unfolds into C-T-E-G during frames 344–525. Table 5.7 lists the .α-helices’ HBs which become weaker, leading to the unfolding of .α-helices.
5.4 Concluding Remarks
231
Lastly, we observe the PT-chains (T-C54.∼C6, P-G2.∼C38) during the 500 .μs MD. Backtracking [66, 225] can be observed from the seven snapshots: at 0th frame T-U21, P-A35; at 100th frame T-A22, P-U34; at 200th frame T-A22, P-U34; at 300th frame T-A22, P-U34; at 400th frame T-G53, P-C3 – T-A22, P-U34 – others T-C54, P-G2; at 500th frame T-A22, P-U34; and at 512th frame T-A22, P-U34. We have shown the interesting backtracking in Fig. 5.4.
5.4 Concluding Remarks During 500 .μs MD, there are the following strong polar contacts among NSP12 and its cofactors NSP7 and NSP8a, NSP8b: A:ASP517-B:LYS79, A:ASP846-D:ARG80, A:ASP851-D:ARG75, C:ASP5-D:LYS97, C:GLU73D:ARG111, C:GLU50-D:ARG190, A:GLU857-D:LYS72, A:GLU436-C:LYS43, and A:ASP274-B:ARG111, where A-chain is NSP12, B-chain is NSP8a, D-chain
Fig. 5.3 The ABCDEF-chains’ residues of optimized NSP12-NSP8-NSP7-NSP13-tpRNA, binding with pRNA and tRNA
232
5 RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA,. . .
Fig. 5.4 NSP12-NSP8-NSP7-NSP13-tpRNA’s PT-chains at frames 0, 100, 200, 300, 400, 500, and 512 during the 500 .μs MD
is NSP8b, and C-chain is NSP7. With each chain of the NSP12-NSP8-NSP7NSP13-tpRNA model, we also get some stronger polar contacts during the 500 .μs MD (Fig. 5.5). The .α-helices of NSP12’s ASP154-ASN158, MET242-THR248, ASN447-ASP454, GLY597-ASN600, and SER768-GLN773, NSP8a’s LEU169SER173, NSP8b’s LEU169-SER173, NSP13a’s ALA446-VAL456, and NSP13b’s ASN516-ILE525 are unfolding during the 500 .μs MD. Backtracking [66, 225] can be observed from the 500 .μs MD.
5.4 Concluding Remarks Table 5.2 SBs in A-, B-, C-, D-, E-, F-chains of the optimized NSP12-NSP8NSP7-NSP13-tpRNA model
233 A:ASP100-A:ARG10
B:ASP143-B:LYS139
E:ASP113-E:LYS414
F:ASP113-F:LYS414
A:ASP100-A:LYS98
B:ASP163-B:LYS165
E:ASP160-E:LYS218
F:ASP160-F:LYS218
A:ASP126-A:LYS47
B:ASP50-B:LYS46
E:ASP207-E:LYS202
F:ASP204-F:LYS524
A:ASP135-A:LYS780
B:GLU77-B:ARG80
E:ASP223-E:ARG186 F:ASP207-F:ARG173
A:ASP135-A:LYS783
E:ASP315-E:ARG332 F:ASP223-F:ARG186
A:ASP140-A:LYS143
C:ASP5-C:LYS2
E:ASP344-E:LYS345
F:ASP315-F:ARG332
A:ASP161-A:LYS160
C:GLU47-C:LYS51
E:ASP369-E:LYS394
F:ASP328-F:LYS329
A:ASP170-A:ARG173 C:GLU74-C:LYS70
E:ASP450-E:LYS462
F:ASP328-F:LYS347
A:ASP194-A:LYS288
E:ASP458-E:LYS460
F:ASP344-F:LYS345
A:ASP235-A:ARG467 D:ASP161-D:LYS165 E:ASP534-E:ARG560 F:ASP369-F:LYS394 A:ASP235-A:ARG735 D:ASP163-D:LYS165 E:ASP580-E:LYS584
F:ASP435-F:LYS271
A:ASP260-A:LYS263
D:ASP50-D:LYS46
E:ASP583-E:LYS584
F:ASP450-F:LYS462
A:ASP274-A:LYS272
D:ASP78-D:ARG75
E:GLU128-E:LYS131 F:ASP483-F:ARG490
A:ASP291-A:ARG735 D:ASP78-D:LYS82
E:GLU136-E:ARG129 F:ASP534-F:ARG560
A:ASP29-A:ARG55
E:GLU136-E:ARG21
F:ASP542-F:LYS508
A:ASP304-A:ARG640 A:ASP274-B:ARG111 E:GLU142-E:LYS139 F:ASP580-F:ARG579 A:ASP358-A:ARG533 A:ASP517-B:LYS72
E:GLU143-E:LYS139 F:ASP583-F:ARG579
A:ASP390-A:ARG392 A:ASP517-B:LYS79
E:GLU168-E:LYS171 F:GLU128-F:LYS131
A:ASP40-A:LYS41
E:GLU197-E:ARG22
A:ASP418-A:LYS890
A:GLU436-C:LYS43
F:GLU136-F:ARG21
E:GLU244-E:LYS276 F:GLU142-F:LYS139
A:ASP421-A:LYS417
E:GLU353-E:LYS347 F:GLU142-F:LYS146
A:ASP452-A:ARG553 A:ASP846-D:ARG80
E:GLU365-E:ARG390 F:GLU143-F:LYS139
A:ASP452-A:ARG624 A:ASP851-D:ARG75
E:GLU375-E:LYS288 F:GLU143-F:LYS146
A:ASP454-A:ARG457 A:ASP851-D:LYS79
E:GLU420-E:ARG427 F:GLU156-F:HIS164
A:ASP465-A:ARG132 A:GLU857-D:LYS72
E:GLU498-E:ARG502 F:GLU162-F:LYS524
A:ASP477-A:ARG640
E:GLU540-E:LYS569 F:GLU168-F:LYS171
A:ASP477-A:LYS641
B:ASP112-A:ARG331 E:GLU551-E:LYS477 F:GLU197-F:ARG339
A:ASP481-A:LYS478 A:ASP484-A:LYS574
F:GLU201-F:ARG161 B:GLU60-F:LYS94
A:ASP499-A:ARG513
F:GLU244-F:LYS276 F:GLU261-F:ARG442
A:ASP523-A:LYS369
C:ASP5-D:LYS97
F:GLU319-F:LYS323
A:ASP618-A:LYS798
C:GLU50-D:ARG190
F:GLU353-F:LYS329
A:ASP623-A:ARG624 C:GLU73-D:ARG111
F:GLU353-F:LYS347
A:ASP623-A:LYS621
F:GLU365-F:ARG390
A:ASP62-A:ARG18
D:ASP112-E:ARG248
A:ASP63-A:LYS59
F:GLU418-F:LYS430 F:GLU420-F:ARG427
A:ASP684-A:ARG631 E:ASP207-F:ARG392
F:GLU447-F:LYS467
A:ASP711-A:LYS714
E:ASP207-F:LYS276
F:GLU498-F:ARG497
A:ASP824-A:LYS821
E:GLU156-F:ARG129
F:GLU540-F:LYS569
A:ASP833-A:HIS439 A:ASP845-A:ARG858 F:GLU244-E:ARG155 A:ASP845-A:LYS849 A:ASP865-A:LYS593 A:ASP879-A:HIS882 A:ASP893-A:HIS892 A:ASP92-A:LYS91 A:GLU136-A:LYS783 A:GLU144-A:LYS121 A:GLU167-A:LYS160 A:GLU180-A:ARG183 A:GLU254-A:ARG285 A:GLU277-A:LYS281 A:GLU278-A:LYS272 A:GLU350-A:ARG349 A:GLU474-A:ARG305 A:GLU474-A:ARG640 A:GLU58-A:ARG118 A:GLU610-A:LYS751 A:GLU61-A:ARG18 A:GLU658-A:ARG631 A:GLU658-A:ARG654 A:GLU665-A:LYS676 A:GLU744-A:ARG726 A:GLU796-A:LYS783 A:GLU811-A:HIS810 A:GLU811-A:LYS438 A:GLU83-A:LYS73 A:GLU894-A:LYS890 A:GLU922-A:LYS871
F:GLU551-F:LYS477
234
5 RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA,. . .
Table 5.3 During the 500 .μs MD, there are nine stronger SBs (with stronger HBs) among the A-B-C-D-E-F-chains of the NSP12-NSP8-NSP7-NSP13-tpRNA model A:ASP517-B:LYS79
LYS79.NZ-ASP517.OD2 31.99%, LYS79.NZ-ASP517.OD1 28.74%
A:ASP846-D:ARG80
ARG80.NH1-ASP846.OD2 25.48%, ARG80.NH1-ASP846.OD1 25.10%, ARG80.NH2-ASP846.OD1 22.80%, ARG80.NH2-ASP846.OD2 22.03%
A:ASP851-D:ARG75
ARG75.NE-ASP851.OD2 34.29%, ARG75.NH2-ASP851.OD1 32.95%, ARG75.NH2-ASP851.OD2 29.31%, ARG75.NE-ASP851.OD1 29.31%
C:ASP5-D:LYS97
LYS97.NZ-ASP5.OD1 33.72%, LYS97.NZ-ASP5.OD2 21.46%
C:GLU73-D:ARG111 ARG111.NE-GLU73.OE2 17.24%, ARG111.NH2-GLU73.OE1 15.13%, ARG111.NE-GLU73.OE1 13.79%, ARG111.NH2-GLU73.OE2 12.45% C:GLU50-D:ARG190 ARG190.NH2-GLU50.OE1 15.33%, ARG190.NH1-GLU50.OE2 14.56%, ARG190.NH1-GLU50.OE1 13.41%, ARG190.NH2-GLU50.OE2 11.49% A:GLU857-D:LYS72
LYS72.NZ-GLU857.OE1 14.37%, LYS72.NZ-GLU857.OE2 12.26%
A:GLU436-C:LYS43
LYS43.NZ-GLU436.OE1 8.05%, LYS43.NZ-GLU436.OE2 6.13%
A:ASP274-B:ARG111 ARG111.NH2-ASP274.OD1 7.47%, ARG111.NH2-ASP274.OD2 6.32%, ARG111.NH1-ASP274.OD2 5.56%, ARG111.NH1-ASP274.OD1 5.17%
Table 5.4 Within each chain, there are some stronger SBs (with stronger HBs) during the 500 .μs MD of the NSP12-NSP8-NSP7-NSP13-tpRNA model B:ASP112-A:ARG331 ARG331.NE-ASP112.O 10.15% B:ASP50-B:LYS46
ASP50.N-LYS46.O 82.95%, LYS46.NZ-ASP50.OD2 47.89%, LYS46.NZ-ASP50.OD1 46.93%, ASP50.OD2-LYS46.NZ 8.24%
B:GLU77-B:ARG80
ARG80.NE-GLU77.OE1 16.67%, ARG80.NE-GLU77.OE2 14.18%, ARG80.NH1-GLU77.OE2 12.07%, ARG80.NH2-GLU77.OE2 11.11%, ARG80.NH1-GLU77.OE1 10.73%, ARG80.NH2-GLU77.OE1 10.54%
B:ASP163-B:LYS165
LYS165.NZ-ASP163.OD1 14.37%, LYS165.NZ-ASP163.OD2 13.03%
B:ASP143-B:LYS139
LYS139.NZ-ASP143.OD1 10.73%, LYS139.NZ-ASP143.OD2 9.96%
C:GLU47-C:LYS51
LYS51.N-GLU47.O 22.22%, LYS51.NZ-GLU47.OE1 15.90%, LYS51.NZ-GLU47.OE2 15.71%
D:ASP50-D:LYS46
ASP50.N-LYS46.O 82.95%, LYS46.NZ-ASP50.OD2 47.89%, LYS46.NZ-ASP50.OD1 46.93%, ASP50.OD2-LYS46.NZ 8.24% -
D:ASP161-D:LYS165 ASP161.N-LYS165.O 43.87%, LYS165.N-ASP161.OD2 26.05%, LYS165.N-ASP161.OD1 23.75%, LYS165.NZ-ASP161.OD2 10.92%, LYS165.NZ-ASP161.OD1 8.24% D:ASP78-D:LYS82
LYS82.N-ASP78.O 41.57%, LYS82.NZ-ASP78.OD2 38.51%, LYS82.NZ-ASP78.OD1 34.67%
D:ASP163-D:LYS165 LYS165.NZ-ASP163.OD1 14.37%, LYS165.NZ-ASP163.OD2 13.03%, D:ASP78-D:ARG75
ARG75.NH1-ASP78.OD1 12.45%, ARG75.NH1-ASP78.OD2 11.30%
E:ASP223-E:ARG186 ARG186.NH2-ASP223.OD1 90.80%, ARG186.NH2-ASP223.OD2 89.08%, ARG186.NE-ASP223.OD2 87.93%, ARG186.NE-ASP223.OD1 85.82% E:GLU143-E:LYS139 GLU143.N-LYS139.O 61.49%, LYS139.NZ-GLU143.OE2 18.20%, LYS139.NZ-GLU143.OE1 15.90% E:GLU353-E:LYS347 LYS347.NZ-GLU353.OE1 54.98%, LYS347.NZ-GLU353.OE2 51.34%, GLU353.OE1-LYS347.NZ 9.20% E:GLU168-E:LYS171 LYS171.NZ-GLU168.OE2 49.62%, LYS171.NZ-GLU168.OE1 45.79%, LYS171.N-GLU168.O 8.81% E:GLU498-E:ARG502 ARG502.N-GLU498.O 45.79%, ARG502.NE-GLU498.OE2 31.61%, ARG502.NE-GLU498.OE1 29.31%, ARG502.NH2-GLU498.OE1 23.75%, ARG502.NH2-GLU498.OE2 21.65%, ARG502.NH1-GLU498.OE2 4.02% E:GLU136-E:ARG21
ARG21.NE-GLU136.OE1 40.42%, ARG21.NE-GLU136.OE2 38.12%, ARG21.NH2-GLU136.OE1 33.14%, ARG21.NH2-GLU136.OE2 32.95%, ARG21.NH1-GLU136.OE2 25.10%, ARG21.NH1-GLU136.OE1 22.99%, GLU136.OE2-ARG21.NE 11.49% -
E:ASP315-E:ARG332 ARG332.NH2-ASP315.OD1 40.23%, ARG332.NH2-ASP315.OD2 38.51%, ARG332.NE-ASP315.OD2 22.03%, ARG332.NE-ASP315.OD1 18.97%, ARG332.NH1-ASP315.OD1 5.75%E:GLU128-E:LYS131 LYS131.NZ-GLU128.OE2 30.08%, LYS131.NZ-GLU128.OE1 29.12% E:GLU244-E:LYS276 LYS276.N-GLU244.O 28.74%, LYS276.NZ-GLU244.OE1 23.75%, LYS276.NZ-GLU244.OE2 21.65% E:ASP534-E:ARG560 ARG560.NH2-ASP534.OD2 27.39%, ARG560.NE-ASP534.OD1 26.25%, ARG560.NH2-ASP534.OD1 24.71%, ARG560.NE-ASP534.OD2 23.75% E:GLU197-E:ARG22
ARG22.NH2-GLU197.OE2 24.71%, ARG22.NH2-GLU197.OE1 23.18%, ARG22.NH1-GLU197.OE2 21.07%, ARG22.NH1-GLU197.OE1 19.35%, ARG22.NE-GLU197.OE1 9.39%, ARG22.NE-GLU197.OE2 8.81%
E:GLU142-E:LYS139 LYS139.NZ-GLU142.OE2 22.61%, LYS139.NZ-GLU142.OE1 20.69% – E:GLU420-E:ARG427 ARG427.NH1-GLU420.OE2 19.54%, ARG427.NH1-GLU420.OE1 18.77%, ARG427.NE-GLU420.OE1 4.60% E:ASP369-E:LYS394
LYS394.NZ-ASP369.OD1 14.37%, LYS394.NZ-ASP369.OD2 10.92% -
E:ASP580-E:LYS584
LYS584.N-ASP580.O 13.60%, LYS584.NZ-ASP580.OD2 8.05%, LYS584.NZ-ASP580.OD1 7.28%
E:ASP450-E:LYS462
LYS462.NZ-ASP450.OD1 10.54%, LYS462.NZ-ASP450.OD2 9.39% -
E:ASP160-E:LYS218
LYS218.NZ-ASP160.OD2 10.34%, LYS218.NZ-ASP160.OD1 8.62% -
E:ASP458-E:LYS460
LYS460.NZ-ASP458.OD1 9.00%, LYS460.NZ-ASP458.OD2 8.62%
E:GLU540-E:LYS569 LYS569.NZ-GLU540.OE2 7.66%, LYS569.NZ-GLU540.OE1 6.70% F:ASP223-F:ARG186 ARG186.NH2-ASP223.OD1 90.80%, ARG186.NH2-ASP223.OD2 89.08%, ARG186.NE-ASP223.OD2 87.93%, ARG186.NE-ASP223.OD1 85.82%
(continued)
5.4 Concluding Remarks
235
Table 5.4 (continued) F:GLU156-F:HIS164
HID164.N-GLU156.O 74.14%, HID164.ND1-GLU156.OE1 18.77%, HID164.ND1-GLU156.OE2 13.98%
F:GLU143-F:LYS139
GLU143.N-LYS139.O 61.49%, LYS139.NZ-GLU143.OE2 18.20%, LYS139.NZ-GLU143.OE1 15.90%
F:GLU353-F:LYS347
LYS347.NZ-GLU353.OE1 54.98%, LYS347.NZ-GLU353.OE2 51.34%, GLU353.OE1-LYS347.NZ 9.20%
F:GLU418-F:LYS430
LYS430.NZ-GLU418.OE2 52.68%, LYS430.NZ-GLU418.OE1 50.77%
F:GLU143-F:LYS146
LYS146.NZ-GLU143.OE2 53.64%, LYS146.NZ-GLU143.OE1 52.87%
F:GLU168-F:LYS171
LYS171.NZ-GLU168.OE2 49.62%, LYS171.NZ-GLU168.OE1 45.79%, LYS171.N-GLU168.O 8.81%
F:ASP583-F:ARG579
ASP583.N-ARG579.O 47.70%, ARG579.NE-ASP583.OD1 35.82%, ARG579.NE-ASP583.OD2 34.48%, ARG579.NH2-ASP583.OD1 18.58%, ARG579.NH2-ASP583.OD2 18.39%, ARG579.NH1-ASP583.OD2 6.90%, ARG579.NH1-ASP583.OD1 4.60%
F:GLU136-F:ARG21
ARG21.NE-GLU136.OE1 40.42%, ARG21.NE-GLU136.OE2 38.12%, ARG21.NH2-GLU136.OE1 33.14%, ARG21.NH2-GLU136.OE2 32.95%, ARG21.NH1-GLU136.OE2 25.10%, ARG21.NH1-GLU136.OE1 22.99%, GLU136.OE2-ARG21.NE 11.49%
F:ASP315-F:ARG332
ARG332.NH2-ASP315.OD1 40.23%, ARG332.NH2-ASP315.OD2 38.51%, ARG332.NE-ASP315.OD2 22.03%, ARG332.NE-ASP315.OD1 18.97%, ARG332.NH1-ASP315.OD1 5.75%
F:ASP328-F:LYS347
LYS347.NZ-ASP328.OD1 30.84%, LYS347.NZ-ASP328.OD2 30.27%, LYS347.NZ-ASP328.O 16.67%
F:GLU128-F:LYS131
LYS131.NZ-GLU128.OE2 30.08%, LYS131.NZ-GLU128.OE1 29.12%
F:GLU244-F:LYS276
LYS276.N-GLU244.O 28.74%, LYS276.NZ-GLU244.OE1 23.75%, LYS276.NZ-GLU244.OE2 21.65%
F:ASP534-F:ARG560
ARG560.NH2-ASP534.OD2 27.39%, ARG560.NE-ASP534.OD1 26.25%, ARG560.NH2-ASP534.OD1 24.71%, ARG560.NE-ASP534.OD2 23.75%
F:GLU261-F:ARG442 ARG442.NH2-GLU261.OE1 23.95%, ARG442.NH1-GLU261.OE2 19.92%, ARG442.NH2-GLU261.OE2 18.20%, ARG442.NH1-GLU261.OE1 15.52% F:GLU142-F:LYS139
LYS139.NZ-GLU142.OE2 22.61%, LYS139.NZ-GLU142.OE1 20.69%
F:ASP542-F:LYS508
LYS508.N-ASP542.OD1 21.07%, LYS508.N-ASP542.OD2 19.54%, LYS508.NZ-ASP542.OD1 8.05%, LYS508.NZ-ASP542.OD2 5.36%
F:GLU420-F:ARG427 ARG427.NH1-GLU420.OE2 19.54%, ARG427.NH1-GLU420.OE1 18.77%, ARG427.NE-GLU420.OE1 4.60% F:ASP369-F:LYS394
LYS394.NZ-ASP369.OD1 14.37%, LYS394.NZ-ASP369.OD2 10.92%
F:ASP435-F:LYS271
LYS271.NZ-ASP435.O 13.03%, LYS271.NZ-ASP435.OD1 9.58%, LYS271.NZ-ASP435.OD2 8.43%
F:GLU142-F:LYS146
LYS146.N-GLU142.O 12.26%
F:ASP450-F:LYS462
LYS462.NZ-ASP450.OD1 10.54%, LYS462.NZ-ASP450.OD2 9.39%
F:ASP160-F:LYS218
LYS218.NZ-ASP160.OD2 10.34%, LYS218.NZ-ASP160.OD1 8.62%
F:GLU353-F:LYS329
LYS329.NZ-GLU353.OE1 7.85%, LYS329.NZ-GLU353.OE2 6.90%
F:GLU540-F:LYS569
LYS569.NZ-GLU540.OE2 7.66%, LYS569.NZ-GLU540.OE1 6.70%
F:ASP483-F:ARG490
ARG490.NH2-ASP483.OD1 7.09%, ARG490.NH2-ASP483.OD2 6.32%, ARG490.NE-ASP483.OD1 5.17%
F:ASP207-F:ARG173
ARG173.NH1-ASP207.OD2 6.90%, ARG173.NH1-ASP207.OD1 6.51%
F:GLU197-F:ARG339 ARG339.NH2-GLU197.OE1 6.90%, ARG339.NH1-GLU197.OE2 6.13%, ARG339.NH2-GLU197.OE2 4.98% F:GLU162-F:LYS524
LYS524.NZ-GLU162.OE1 5.94%, LYS524.NZ-GLU162.OE2 5.36%
A:ASP421-A:LYS417
ASP421.N-LYS417.O 60.15%, LYS417.NZ-ASP421.OD2 30.08%, LYS417.NZ-ASP421.OD1 22.80%
A:GLU658-A:ARG654 GLU658.N-ARG654.O 59.00%, ARG654.NH2-GLU658.OE2 27.59%, ARG654.NH2-GLU658.OE1 21.26% A:GLU665-A:LYS676 LYS676.N-GLU665.O 55.94%, LYS676.NZ-GLU665.OE2 42.91%, LYS676.NZ-GLU665.OE1 20.31% A:ASP390-A:ARG392 ARG392.NE-ASP390.OD2 52.49%, ARG392.NH2-ASP390.OD1 45.79%, ARG392.NE-ASP390.OD1 32.95%, ARG392.NH2-ASP390.OD2 30.08% A:ASP304-A:ARG640 ARG640.NE-ASP304.OD1 47.51%, ARG640.NE-ASP304.OD2 42.15%, ARG640.NH2-ASP304.OD2 40.23%, ARG640.NH2-ASP304.OD1 34.67% A:ASP358-A:ARG533 ARG533.NE-ASP358.OD2 44.06%, ARG533.NH2-ASP358.OD1 40.04%, ARG533.NE-ASP358.OD1 38.51%, ARG533.NH2-ASP358.OD2 36.59% A:GLU474-A:ARG640 ARG640.NH2-GLU474.OE2 42.72%, ARG640.NH1-GLU474.OE1 41.00%, ARG640.NH2-GLU474.OE1 39.27%, ARG640.NH1-GLU474.OE2 38.12% A:GLU58-A:ARG118
ARG118.NH2-GLU58.OE2 41.95%, ARG118.NH2-GLU58.OE1 39.85%, ARG118.NE-GLU58.OE2 39.27%, ARG118.NE-GLU58.OE1 39.08%
A:GLU277-A:LYS281 LYS281.N-GLU277.O 39.46% A:GLU658-A:ARG631 ARG631.NH2-GLU658.OE1 37.74%, ARG631.NH2-GLU658.OE2 30.65% A:ASP499-A:ARG513 ASP499.OD1-ARG513.NE 36.97%, ARG513.NE-ASP499.OD1 36.97%, ARG513.NE-ASP499.OD2 32.38%, ARG513.NH2-ASP499.OD2 31.42%, ARG513.NH2-ASP499.OD1 31.23% A:ASP845-A:LYS849
LYS849.NZ-ASP845.OD2 34.87%, YS849.NZ-ASP845.OD1 33.72%, ASP845.OD2-LYS849.NZ 11.49%
A:ASP100-A:ARG10
ARG10.NH1-ASP100.OD1 34.10%, ARG10.NH2-ASP100.OD2 31.23%, ARG10.NH1-ASP100.OD2 28.54%, ARG10.NH2-ASP100.OD1 26.05%
A:GLU796-A:LYS783 LYS783.NZ-GLU796.OE1 33.33%, LYS783.NZ-GLU796.OE2 28.35% A:GLU744-A:ARG726 ARG726.NH1-GLU744.OE1 32.95%, ARG726.NH1-GLU744.OE2 31.99%, ARG726.NH2-GLU744.OE2 30.65%, ARG726.NH2-GLU744.OE1 28.54% A:ASP29-A:ARG55
ARG55.NE-ASP29.OD1 31.61%, ARG55.NE-ASP29.OD2 29.50%, ARG55.NH2-ASP29.OD2 27.01%, ARG55.NH2-ASP29.OD1 25.48%
A:GLU894-A:LYS890 LYS890.NZ-GLU894.OE1 31.23%, LYS890.NZ-GLU894.OE2 26.05%, GLU894.N-LYS890.O 18.58%, GLU894.OE1-LYS890.NZ 12.07%
(continued)
236
5 RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA,. . .
Table 5.4 (continued) A:ASP477-A:ARG640 ARG640.NH1-ASP477.OD2 27.78%, ARG640.NH1-ASP477.OD1 23.75% A:ASP865-A:LYS593
LYS593.NZ-ASP865.OD2 27.59%, LYS593.NZ-ASP865.OD1 26.63%, ASP865.OD2-LYS593.NZ 11.49%
A:GLU144-A:LYS121 LYS121.NZ-GLU144.OE1 27.39%, LYS121.NZ-GLU144.OE2 26.82% A:GLU350-A:ARG349 ARG349.NE-GLU350.OE1 27.39%, ARG349.NE-GLU350.OE2 26.25% A:GLU180-A:ARG183 ARG183.NE-GLU180.OE1 26.63%, ARG183.NH2-GLU180.OE2 26.25%, ARG183.NE-GLU180.OE2 18.58%, ARG183.NH2-GLU180.OE1 17.43% A:GLU922-A:LYS871 LYS871.NZ-GLU922.OE1 20.31%, LYS871.NZ-GLU922.OE2 17.43% A:GLU254-A:ARG285 ARG285.NH1-GLU254.OE2 18.01%, ARG285.NH2-GLU254.OE1 17.82%, ARG285.NH2-GLU254.OE2 17.24%, ARG285.NH1-GLU254.OE1 13.79%, ARG285.NE-GLU254.OE1 5.75% A:ASP260-A:LYS263
LYS263.N-ASP260.O 17.05%, LYS263.NZ-ASP260.OD1 12.64%, LYS263.NZ-ASP260.OD2 8.62%
A:ASP618-A:LYS798
ASP618.N-LYS798.O 17.05%, LYS798.NZ-ASP618.OD2 9.39%, LYS798.NZ-ASP618.OD1 6.70%
A:ASP454-A:ARG457 ARG457.NH2-ASP454.OD1 16.86%, ARG457.NH2-ASP454.OD2 14.75%, ARG457.NH1-ASP454.OD2 13.79%, ARG457.NH1-ASP454.OD1 12.07% A:ASP274-A:LYS272
LYS272.NZ-ASP274.OD1 15.90%, LYS272.NZ-ASP274.OD2 10.92%
A:ASP879-A:HIS882
HID882.ND1-ASP879.OD1 13.98%, HID882.ND1-ASP879.OD2 13.79%
A:ASP235-A:ARG467 ARG467.NH2-ASP235.OD1 13.41%, ARG467.NH2-ASP235.OD2 12.64%, ARG467.NH1-ASP235.OD2 11.30%, ARG467.NH1-ASP235.OD1 10.92% A:ASP135-A:LYS780
LYS780.NZ-ASP135.OD2 13.22%, LYS780.NZ-ASP135.OD1 11.30%
A:ASP170-A:ARG173 ARG173.NH2-ASP170.OD2 13.22%, ARG173.NH2-ASP170.OD1 11.69%, ARG173.NE-ASP170.OD1 7.66%, ARG173.NE-ASP170.OD2 5.56% A:ASP291-A:ARG735 ARG735.NH2-ASP291.OD1 12.84%, ARG735.NH2-ASP291.OD2 11.88%, ARG735.NH1-ASP291.OD2 5.56%, ARG735.NH1-ASP291.OD1 4.60% A:ASP481-A:LYS478
LYS478.NZ-ASP481.OD2 12.26%, LYS478.NZ-ASP481.OD1 11.88%
A:GLU278-A:LYS272 LYS272.NZ-GLU278.OE2 11.88%, LYS272.NZ-GLU278.OE1 9.39% A:ASP161-A:LYS160
LYS160.NZ-ASP161.OD1 11.69%, LYS160.NZ-ASP161.OD2 10.34%
A:GLU474-A:ARG305 ARG305.NE-GLU474.OE1 9.39%, ARG305.NE-GLU474.OE2 5.75%, ARG305.NH1-GLU474.OE2 4.98% A:ASP63-A:LYS59
LYS59.NZ-ASP63.OD2 9.20%, LYS59.NZ-ASP63.OD1 8.24%
A:ASP235-A:ARG735 ARG735.NH2-ASP235.OD2 8.81%, ARG735.NH2-ASP235.OD1 7.85% A:ASP452-A:ARG624 ARG624.NH1-ASP452.OD1 8.81%, ARG624.NH2-ASP452.OD2 7.09% A:ASP40-A:LYS41
LYS41.NZ-ASP40.OD2 8.62%, LYS41.NZ-ASP40.OD1 5.56%
A:ASP465-A:ARG132 ARG132.NH2-ASP465.OD2 8.24%, ARG132.NH2-ASP465.OD1 6.13% A:ASP194-A:LYS288
LYS288.NZ-ASP194.OD1 7.66%, LYS288.NZ-ASP194.OD2 5.17%
A:GLU136-A:LYS783 LYS783.NZ-GLU136.OE2 7.47%, LYS783.NZ-GLU136.OE1 5.56% A:ASP140-A:LYS143
LYS143.NZ-ASP140.OD1 6.90%, LYS143.NZ-ASP140.OD2 6.32%
Table 5.5 Within each chain, there are some stronger SBs (with stronger HBs) during the 500 .μs MD of the NSP12-NSP8-NSP7-NSP13-tpRNA model (continuation) A:ASP135-A:LYS783
LYS783.NZ-ASP135.OD1 6.70%, LYS783.NZ-ASP135.OD2 6.70%
A:ASP711-A:LYS714
LYS714.NZ-ASP711.OD1 6.70%, LYS714.NZ-ASP711.OD2 5.17%
A:ASP484-A:LYS574
LYS574.NZ-ASP484.OD1 5.17%
A:GLU610-A:LYS751
LYS751.NZ-GLU610.OE2 4.79%, LYS751.NZ-GLU610.OE1 4.60%
GLU155.N-LEU189.O 69.16%
TYR306.N-VAL356.O 68.97%
LEU25.N-LEU14.O 68.77%
TYR925.OH-ILE864.O 68.77%
GLU23.N-GLN19.O 68.58%
ASN37.N-VAL33.O 68.39%
TYR294.OH-ASN314.OD1 68.39%
TYR396.N-LYS276.O 67.82%
LEU500.N-VAL496.O 67.62%
TYR299.OH-TYR269.O 67.62%
LYS46.N-LEU42.O 67.62%
TYR185.N-TYR224.O 67.62%
THR199.N-ARG212.O 67.62%
ILE35.N-TYR31.O 67.43%
THR566.OG1-ASN562.O 67.43%
ASN43.N-LYS39.O 67.05%
ALA110.N-PHE106.O 66.86%
ILE333.N-PHE357.O 66.86%
PHE546.N-LEU573.O 66.67%
ALA123.N-ASP119.O 66.67%
LEU38.N-VAL34.O 66.48%
GLY400.N-LEU280.O 66.48%
VAL209.N-LEU163.O 66.09%
ALA512.N-LYS500.O 65.90%
ALA423.N-PHE419.O 65.52%
GLU142.N-LEU138.O 65.33%
GLY3.N-THR12.O 65.13%
LEU91.N-MET87.O 65.13%
SER385.OG-ALA237.O 64.75%
VAL193.N-ARG186.O 64.75%
ALA74.N-MET70.O 64.75%
MET576.N-MET474.O 64.18%
ILE334.N-ASN349.OD1 64.18%
LEU98.N-MET94.O 64.18%
GLY184.N-GLY196.O 63.98%
ASN423.ND2-ALA379.O 63.98%
LEU885.N-PHE881.O 63.79%
TYR246.OH-LYS394.O 63.41%
SER331.OG-LYS347.O 63.41%
ARG75.N-TYR71.O 63.41%
THR141.OG1-THR137.O 91.57%
ARG186.NH2-ASP223.OD1 90.80%
ARG186.NH2-ASP223.OD2 89.08%
LEU65.N-PHE81.O 88.31%
CYM5.N-SER10.O 87.93%
ARG186.NE-ASP223.OD2 87.93%
LEU43.N-ARG15.O 87.55%
THR12.OG1-LEU25.O 85.82%
ARG186.NE-ASP223.OD1 85.82%
CYS30.N-CYM26.O 85.06%
PHE373.N-VAL397.O 84.87%
ALA134.N-LEU130.O 84.87%
VAL397.N-VAL371.O 84.67%
ILE132.N-LEU184.O 84.10%
ARG497.N-ILE493.O 83.91%
THR307.N-VAL372.O 83.14%
ASP50.N-LYS46.O 82.95%
ILE185.N-VAL160.O 82.57%
VAL371.N-HID395.O 81.61%
LEU280.N-TYR398.O 81.42%
CYS426.N-ASN423.OD1 81.03%
LEU573.N-VAL544.O 80.08%
CYS574.N-PHE472.O 79.89%
VAL372.N-VAL305.O 79.89%
ASN51.N-TYR70.O 79.31%
PHE357.N-SER331.O 79.12%
TYR306.OH-ALA292.O 79.12%
PHE225.N-ALA152.O 78.93%
TYR64.N-TYR71.O 78.93%
LYS473.NZ-TYR582.O 78.93%
LEU325.N-ALA321.O 78.54%
ILE545.N-VAL510.O 78.35%
ILE156.N-THR145.O 78.35%
PHE511.N-PRO529.O 77.78%
LYS569.N-TYR541.O 77.78%
ASN104.N-ASN100.O 77.59%
TRP154.N-PHE147.O 77.59%
ILE512.N-ILE545.O 77.20%
ALA16.N-TYR12.O 76.82%
CYS142.N-TYR138.O 76.44%
PHE348.N-GLY352.O 57.47%
LEU184.N-ILE132.O 57.47%
GLN56.N-ASP52.O 57.47%
VAL44.N-LYS40.O 57.47%
TYR269.N-ASN265.O 57.47%
THR68.N-ASP64.O 57.66%
THR701.N-CYS697.O 57.66%
VAL700.N-ILE696.O 57.66%
LEU138.N-ALA134.O 57.85%
ARG390.N-VAL386.O 57.85%
THR111.OG1-ASN107.O 57.85%
LYS131.N-THR127.O 58.24%
TYR398.N-SER278.O 58.24%
TYR129.N-ALA125.O 58.43%
GLN470.N-VAL570.O 58.81%
PHE90.N-LEU83.O 58.81%
TYR87.N-GLU83.O 58.81%
GLU658.N-ARG654.O 59.00%
PHE70.N-PHE56.O 59.20%
VAL330.N-VAL115.O 59.39%
ALA14.N-PRO10.O 59.39%
VAL473.N-LEU469.O 59.58%
VAL210.N-GLU201.O 59.77%
GLN19.N-PHE15.O 59.77%
ASP315.N-HID311.O 59.96%
ARG443.NH1-THR566.O 59.96%
ILE493.N-ASN489.O 59.96%
ASP421.N-LYS417.O 60.15%
GLY222.N-VAL154.O 60.34%
LYS79.N-ARG75.O 60.34%
ALA86.N-LYS82.O 60.34%
LEU428.N-SER424.O 60.34%
THR183.N-VAL226.O 60.34%
VAL353.N-ASN297.OD1 60.34%
LEU103.N-ASN100.OD1 60.54%
TYR246.N-MET274.O 60.54%
GLU60.N-GLN56.O 60.54%
GLN281.N-MET436.O 60.54%
LYS430.NZ-GLU420.OE1 60.73%
MET62.N-LYS58.O 60.92%
MET633.N-MET629.O 52.49%
THR137.OG1-ASP134.OD1 52.49%
SER57.OG-SER54.O 52.49%
ILE572.N-GLN470.O 52.68%
SER263.N-SER259.O 52.68%
LYS430.NZ-GLU418.OE2 52.68%
SER523.N-ASN519.O 52.68%
CYS697.N-VAL693.O 52.68%
LYS146.NZ-GLU143.OE1 52.87%
VAL34.N-CYS30.O 52.87%
LEU329.N-GLY345.O 53.07%
THR89.N-SER85.O 53.26%
LYS40.N-LYS36.O 53.26%
THR431.N-ARG427.O 53.26%
TYR237.OH-GLN210.OE1 53.45%
ASN507.N-GLY503.O 53.45%
ASN705.N-THR701.O 53.45%
THR137.OG1-ASP134.OD2 53.45%
ARG303.N-ASP369.OD2 53.45%
ASP525.N-TYR521.O 53.64%
LEU389.N-MET129.O 53.64%
TYR277.N-GLN243.OE1 53.64%
LYS146.NZ-GLU143.OE2 53.64%
ILE304.N-GLN354.O 53.64%
MET196.N-PHE192.O 53.83%
ARG178.NE-GLU201.OE1 54.02%
LYS39.N-LEU35.O 54.21%
CYS464.N-ASN312.OD1 54.41%
VAL667.N-TYR674.O 54.41%
MET129.N-LEU387.O 54.41%
SER36.OG-ASP32.O 54.60%
ASN568.N-SER564.O 54.60%
MET668.N-THR540.O 54.60%
TYR421.N-GLU418.O 54.60%
VAL26.N-TYR22.O 54.79%
ASN356.N-THR344.O 54.79%
CYS765.N-SER754.O 54.79%
VAL424.N-TYR420.O 54.79%
LYS347.NZ-GLU353.OE1 54.98%
PHE92.N-GLN88.O 54.98%
Table 5.6 During the 500 .μs MD of the NSP12-NSP8-NSP7-NSP13-tpRNA model, the strong HBs with occupancy rates (.≥50%) are
(continued)
5.4 Concluding Remarks 237
ILE107.N-LEU103.O 62.64%
ASN28.N-GLN24.O 62.64%
MET87.N-VAL83.O 62.45%
THR187.N-GLN158.O 62.26%
TYR48.OH-VAL42.O 62.26%
SER331.N-TYR355.O 62.07%
ALA656.N-PHE652.O 62.07%
LEU83.N-LEU63.O 62.07%
VAL535.N-ASN356.OD1 61.88%
PHE291.N-GLY287.O 61.69%
LEU322.N-CYS318.O 61.69%
LEU891.N-TYR887.O 61.69%
LEU673.N-ALA399.O 61.69%
LYS72.N-THR68.O 61.69%
GLU143.N-LYS139.O 61.49%
ASN388.ND2-PRO238.O 61.30%
ILE888.N-TYR884.O 61.30%
VAL226.N-THR183.O 61.30%
GLY294.N-HID290.O 61.11%
CYS358.N-TYR306.O 74.90%
SER166.N-THR153.O 74.52%
ALA53.N-PHE49.O 74.33%
HID164.N-GLU156.O 74.14%
ILE399.N-PHE373.O 73.95%
LEU128.N-ALA188.O 73.37%
LEU95.N-LEU91.O 72.99%
ALA191.N-LEU153.O 72.99%
GLN157.N-THR187.O 72.80%
VAL305.N-ILE370.O 72.61%
ILE565.N-PHE561.O 72.61%
ASN108.N-ASN104.O 72.03%
CYS318.N-VAL314.O 72.03%
ASN562.N-VAL558.O 71.84%
ARG186.NH2-LYS218.O 71.84%
ASN349.N-ARG332.O 71.65%
VAL186.N-VAL130.O 70.69%
PHE472.N-ILE572.O 70.50%
TYR71.N-MET67.O 70.50%
THR153.N-SER166.O 60.92%
MET67.N-ALA63.O 62.64%
TYR120.OH-TRP114.O 75.10%
PHE182.N-TYR198.O 70.31%
HID113.N-PHE102.O 50.00%
LYS783.N-ILE779.O 62.84%
GLY66.N-SER69.O 75.29%
SER41.N-LYS37.O 61.11%
THR137.N-PHE133.O 62.84%
LYS139.N-TYR135.O 75.48%
VAL167.N-VAL159.O 60.92%
ARG560.N-CYS556.O 63.03%
ALA140.N-GLU136.O 75.48%
MET566.N-ILE562.O 70.50%
TYR476.N-MET576.O 63.03%
ALA321.N-LEU317.O 75.48%
VAL130.N-VAL186.O 70.31%
ASP358.N-ASN534.OD1 50.00%
GLN270.N-VAL266.O 63.22%
LEU59.N-MET55.O 76.05%
TYR355.N-LYS329.O 55.17%
GLN88.N-THR84.O 55.17%
GLN354.NE2-ALA302.O 55.17%
PHE745.N-PHE741.O 55.36%
THR9.OG1-ASP5.O 55.36%
VAL563.N-ASN559.O 55.56%
LYS676.N-GLU665.O 55.94%
LYS430.NZ-GLU420.OE2 55.94%
THR501.OG1-ARG497.O 56.13%
THR37.OG1-HID33.O 56.32%
TYR595.N-MET924.O 56.32%
SER115.N-ASP100.O 56.51%
ARG567.NE-SER539.O 56.51%
THR9.N-ASP5.O 56.51%
ARG507.NE-LEU500.O 56.51%
ASN416.N-CYS842.O 56.70%
TYR382.OH-MET233.O 56.70%
ARG186.N-VAL193.O 56.70%
VAL387.N-ASP383.O 56.70%
THR850.OG1-ILE847.O 56.90%
LYS36.N-GLU32.O 56.90%
PHE694.N-ALA690.O 56.90%
VAL72.N-CYS54.O 57.09%
HID395.N-ASP369.O 57.09%
LEU56.N-MET52.O 57.28%
VAL476.N-VAL472.O 50.00%
LYS545.N-ARG555.O 50.00%
THR359.OG1-ASN361.OD1 50.00%
SER47.N-ASN43.O 50.19%
ALA522.N-GLN518.O 50.57%
ILE579.N-LEU575.O 50.57%
GLN243.NE2-TYR277.O 50.57%
LYS430.NZ-GLU418.OE1 50.77%
VAL33.N-TRP29.O 50.77%
GLN492.N-ASN489.OD1 50.96%
ILE333.N-PHE340.O 50.96%
TYR374.N-GLU370.O 50.96%
MET124.N-GLN210.O 51.15%
VAL233.N-GLY203.O 51.15%
TYR71.N-TYR64.O 51.15%
ARG303.N-ASP369.OD1 51.34%
GLU498.N-GLY494.O 51.34%
LYS347.NZ-GLU353.OE2 51.34%
THR144.OG1-ALA140.O 51.72%
SER635.N-ARG631.O 51.72%
VAL160.N-ILE185.O 51.72%
ASN691.N-THR687.O 51.72%
CYS669.N-SER672.O 51.92%
TYR138.N-ASP134.O 52.11%
ALA21.N-THR17.O 52.11%
ALA575.N-PHE546.O 52.11%
ARG750.N-TYR746.O 52.30%
ARG392.NE-ASP390.OD2 52.49%
ILE575.N-PHE546.O 52.49%
SER278.N-TYR396.O 63.22%
ARG116.N-VAL71.O 52.49%
TYR198.N-PHE182.O 76.05%
ARG57.N-ALA53.O 57.28%
ILE109.N-ASP105.O 63.22%
MET429.N-VAL425.O 76.05%
LEU117.N-MET129.O 57.28%
ALA368.N-ARG392.O 63.41%
VAL154.N-ASP223.O 76.25%
Table 5.6 (continued)
238 5 RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA,. . .
5.4 Concluding Remarks
239
Table 5.7 The following .α-helices’ HBs become weaker, leading to the unfolding of .α-helices A:ASP154
ASN158.N-ASP154.O 8.81%
A:ASP155
LYS159.N-ASP155.O 7.85%
A:TYR156
LYS143.NZ-TYR156.O 11.30%, TYR156.N-ASP153.O 5.36%
A:PHE157
PHE157.N-ASP153.O 8.24%
A:ASN158
ASN158.N-ASP154.O 8.81%
A:LEU241
ILE244.N-LEU241.O 14.37%, LEU245.N-LEU241.O 14.18%, LEU241.N-TYR237.O 5.56%
A:MET242
MET242.N-TYR238.O 27.39%, LEU245.N-MET242.O 6.70%, THR246.N-MET242.O 6.70%, THR246.OG1-MET242.O 4.98%
A:PRO243
LEU247.N-PRO243.O 19.54%, TYR788.OH-PRO243.O 8.62%
A:ILE244
THR248.OG1-ILE244.O 35.63%, THR248.N-ILE244.O 31.61%, ILE244.N-LEU241.O 14.37%
A:LEU245
LEU245.N-LEU241.O 14.18%, ALA250.N-LEU245.O 11.69%, LEU245.N-MET242.O 6.70%
A:THR246
MET463.N-THR246.OG1 42.34%, THR246.N-MET242.O 6.70%, ASN791.ND2-THR246.O 6.70%
A:LEU247
LEU247.N-PRO243.O 19.54%, ARG249.NH2-LEU247.O 7.47%
A:THR248
THR248.OG1-ILE244.O 35.63%, THR248.N-ILE244.O 31.61%
A:ASN447
SER451.N-ASN447.O 40.04%, GLN408.N-ASN447.OD1 23.56%, ASN447.ND2-ALA406.O 13.98%, ILE450.N-ASN447.O 7.66%, ALA449.N-ASN447.OD1 5.56%
A:ALA448
ALA448.N-GLN408.O 25.29%
A:ALA449
ALA449.N-ASN447.OD1 5.56%
A:ILE450
ARG392.NH1-ILE450.O 48.47%, ILE450.N-ASN447.O 7.66%
A:SER451
SER451.N-ASN447.O 40.04%
A:ASP452
ARG624.NH1-ASP452.OD1 8.81%, ARG624.NH2-ASP452.OD2 7.09%, THR556.N-ASP452.OD2 6.13%, THR556.OG1-ASP452.OD2 4.60%
A:TYR453
TYR453.N-ALA449.O 4.41%
A:ASP454
ARG457.NH2-ASP454.OD1 16.86%, ARG457.NH2-ASP454.OD2 14.75%, ARG457.NH1-ASP454.OD2 13.79%, THR556.N-ASP454.O 12.64%, ARG457.NH1-ASP454.OD1 12.07%, ARG553.NE-ASP454.OD2 12.07%, ARG553.NE-ASP454.OD1 11.88%, ARG553.NH2-ASP454.OD2 11.49%, ARG553.NH2-ASP454.OD1 11.49%
A:TYR455
SER681.OG-TYR455.O 23.75%
A:TYR456
ARG457.NH1-TYR456.O 10.34%
A:ARG457
ARG457.N-THR680.O 27.97%, ARG457.NE-CYS622.O 19.54%, ARG457.NH2-ASP454.OD1 16.86%, ARG457.NH2-ASP454.OD2 14.75%, ARG457.NH1-ASP454.OD2 13.79%, ARG457.NH1-ASP454.OD1 12.07%, ARG457.NH1-TYR456.O 10.34%, ARG457.NH1-ASP760.OD1 5.75%, ARG457.NH1-ASP760.OD2 5.36%, THR680.N-ARG457.O 4.98%, ARG457.NH2-ASP760.OD2 4.60%
A:TYR458
ALA625.N-TYR458.O 14.18%
A:ASN459
ASN459.N-GLY678.O 21.84%, ASN459.ND2-MET626.O 16.86%, ASN459.N-SER453.O 16.09%
A:GLY596
ASN600.N-GLY596.O 32.57%
A:GLY597
MET601.N-GLY597.O 11.49%, GLY597.N-PHE594.O 8.24%
A:TRP598
LEU602.N-TRP598.O 23.18%, TRP598.NE1-THR817.OG1 5.94%
A:HID599
LYS603.N-HID599.O 6.51%
A:ASN600
ASN600.N-GLY596.O 32.57%, LYS603.NZ-ASN600.OD1 9.96%, THR604.OG1-ASN600.O 7.09%, THR604.N-ASN600.O 5.17%, LYS603.N-ASN600.OD1 4.79%
A:MET601
THR604.OG1-MET601.O 15.33%, MET601.N-GLY597.O 11.49%, VAL605.N-MET601.O 9.77%, THR604.N-MET601.O 4.60%
A:LEU602
LEU602.N-TRP598.O 23.18%, TYR606.N-LEU602.O 22.41%
A:LYS603
LYS603.NZ-ASN600.OD1 9.96%, SER607.OG-LYS603.O 7.28%, LYS603.N-HID599.O 6.51%, LYS603.N-ASN600.OD1 4.79%
A:THR604
THR604.OG1-MET601.O 15.33%, ALA585.N-THR604.OG1 14.75%, SER754.OG-THR604.O 9.20%, THR604.OG1-ASN600.O 7.09%, THR604.N-ASN600.O 5.17%, THR604.N-MET601.O 4.60%
A:VAL605
VAL605.N-MET601.O 9.77%
A:TYR606
TYR606.N-LEU602.O 22.41%
A:SER607
SER607.OG-LYS603.O 7.28%, ARG750.NH1-SER607.O 5.17%
A:ASP608
LYS751.NZ-ASP608.O 9.39%
A:ASN767
ASN611.N-ASN767.OD1 23.95%, ASN767.N-HID752.O 15.90%, TYR770.N-ASN767.OD1 13.79%, ASN767.ND2-GLU610.O 9.39%, ALA771.N-ASN767.O 8.43%, ASN767.ND2-THR769.OG1 7.28%
A:SER768
SER768.N-ASN611.O 19.54%, SER772.N-SER768.O 16.67%, SER768.OG-ASN611.O 6.13%
A:THR769
GLN773.N-THR769.O 9.00%, ASN767.ND2-THR769.OG1 7.28%
A:TYR770
LEU775.N-TYR770.O 14.56%, TYR770.N-ASN767.OD1 13.79%
A:ALA771
ALA771.N-ASN767.O 8.43%
A:SER772
SER772.N-SER768.O 16.67%
A:GLN773
GLN773.N-THR769.O 9.00%
A:GLY774 A:LEU775
LEU775.N-TYR770.O 14.56%
A:VAL776
ASN713.N-VAL776.O 6.32%
A:ALA777
ALA777.N-ASN703.OD1 18.58%
A:SER778
SER778.N-ASN781.OD1 21.84%, PHE782.N-SER778.O 15.71%
B/D:LEU169 SER173.N-LEU169.O 22.22%, SER173.OG-LEU169.O 16.48% B/D:SER170 B/D:GLU171 SER177.OG-GLU171.O 16.28%, GLU171.N-GLN168.O 15.33%, ASN176.ND2-GLU171.O 10.15% B/D:ILE172 ILE172.N-GLN168.O 19.35%, TYR135.OH-ILE172.O 7.85% B/D:SER173 SER173.N-LEU169.O 22.22%, SER173.OG-LEU169.O 16.48%
(continued)
240
5 RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA,. . .
Table 5.7 (continued) E:ALA446
ASP450.N-ALA446.O 30.65%
E:GLU447
THR451.OG1-GLU447.O 41.38%, LYS584.NZ-GLU447.OE2 19.35%, LYS584.NZ-GLU447.OE1 15.52%, THR451.N-GLU447.O 14.37%
E:ILE448
VAL452.N-ILE448.O 45.40%, ILE448.N-PRO445.O 8.24%
E:VAL449
SER453.N-VAL449.O 41.00%, VAL449.N-PRO445.O 23.56%, SER453.OG-VAL449.O 10.73%
E:ASP450
ASP450.N-ALA446.O 30.65%, ALA454.N-ASP450.O 23.95%, LYS462.NZ-ASP450.OD1 10.54%, LYS460.NZ-ASP450.OD2 9.77%, LYS462.NZ-ASP450.OD2 9.39%, LYS460.NZ-ASP450.OD1 9.20%
E:THR451
THR451.OG1-GLU447.O 41.38%, LEU455.N-THR451.O 36.21%, THR451.N-GLU447.O 14.37%
E:VAL452
VAL452.N-ILE448.O 45.40%, VAL456.N-VAL452.O 39.66%, TYR457.N-VAL452.O 12.45%, LEU455.N-VAL452.O 7.09%
E:SER453
SER453.N-VAL449.O 41.00%, ASN459.N-SER453.O 16.09%, SER453.OG-VAL449.O 10.73%, LEU461.N-SER453.OG 5.75%
E:ALA454
ALA454.N-ASP450.O 23.95%
E:LEU455
LEU455.N-THR451.O 36.21%, LEU455.N-VAL452.O 7.09%
E:VAL456
VAL456.N-VAL452.O 39.66%
F:ASN516
ALA520.N-ASN516.O 38.51%, ASN519.N-ASN516.OD1 17.24%
F:SER517
VAL521.N-SER517.O 15.52%, SER517.OG-SER485.O 7.47%
F:GLN518
ALA522.N-GLN518.O 50.57%, SER513.OG-GLN518.OE1 28.74%, THR547.OG1-GLN518.OE1 15.71%, GLN518.NE2-SER486.O 13.41%
F:ASN519
SER523.N-ASN519.O 52.68%, SER523.OG-ASN519.O 23.18%, ASN519.N-ASN516.OD1 17.24%, ASN519.N-TYR515.O 13.60%, ASN519.ND2-SER513.O 13.60%, ASN519.ND2-PRO514.O 13.03%, SER513.OG-ASN519.OD1 7.66%, ALA522.N-ASN519.OD1 6.70%, ASN519.ND2-GLN531.O 4.60%
F:ALA520
ALA520.N-ASN516.O 38.51%, LYS524.N-ALA520.O 28.54%
F:VAL521
ILE525.N-VAL521.O 35.44%, VAL521.N-SER517.O 15.52%, LEU526.N-VAL521.O 13.03%
F:ALA522
ALA522.N-GLN518.O 50.57%, LEU528.N-ALA522.O 35.82%, LEU526.N-ALA522.O 29.12%, ALA522.N-ASN519.OD1 6.70%
F:SER523
SER523.N-ASN519.O 52.68%, SER523.OG-ASN519.O 23.18%, LEU528.N-SER523.O 11.49%, THR530.N-SER523.OG 7.09%, SER523.OG-LEU528.O 4.98%
F:LYS524
LYS524.N-ALA520.O 28.54%, LYS524.NZ-GLN270.OE1 7.09%, LYS524.NZ-GLU162.OE1 5.94%, LYS524.NZ-LEU252.O 5.36%, LYS524.NZ-GLU162.OE2 5.36%
F:ILE525
ILE525.N-VAL521.O 35.44%, ARG497.NH2-ILE525.O 14.37%
F:LEU526
LEU526.N-ALA522.O 29.12%, LEU526.N-VAL521.O 13.03%
E/F:VAL533
GLN537.NE2-VAL533.O 7.09%
E/F:ASP534
GLN537.NE2-ASP534.O 8.24%, THR532.OG1-ASP534.OD1 6.51%, THR532.OG1-ASP534.OD2 6.13%, ARG560.NE-ASP534.OD2 23.75%, ARG560.NH2-ASP534.OD1 24.71%, ARG560.NE-ASP534.OD1 26.25%, ARG560.NH2-ASP534.OD2 27.39%
E/F:SER535
THR532.N-SER535.OG 35.63%, SER535.OG-GLN531.OE1 23.75%, SER535.N-THR532.OG1 21.26%, SER535.OG-THR532.OG1 6.70%
E/F:SER536
SER536.OG-THR532.O 45.02%, TYR541.OH-SER536.OG 30.46%, SER539.N-SER536.O 17.82%, SER536.N-THR532.O 14.18%
5.4 Concluding Remarks
241
Fig. 5.5 During the 500 .μs MD, there are nine stronger SBs (with stronger HBs) among the A-BC-D-E-F-chains
242
5 RNA Helicase Binding with RdRp, NSP7, NSP8a, NSP8b, pRNA, tRNA,. . .
Fig. 5.5 (continued)
Chapter 6
RNA Helicase Binding with ADP-Mg2+ , ATP-Mg2+ , and RNA .
.
Abstract This chapter studied the six models of model-NSP13-ATPMg.2+ RNA, model-NSP13-ADPMg.2+ -RNA, model-NSP13-ATPMg.2+ , model-NSP13ADPMg.2+ , model-NSP13.1-open-ADPMg.2+ , and model-NSP13.1-closeADPMg.2+ by using optimization and MD technologies. NSP13’s segments such as ASN51-GLY91, 151–221, 471–531, and 441/461/481/541/551–581 have larger root mean square fluctuations during MDs. NSP13’s residues 139, 142, 177, 179, 180, 230, 231, 311, 337, 361, 382, 383, 390, 408, 409, 410, 485, 486, 514, 515, 516, 532, 534, 535, and 554 bind RNA-6CCCAUGUG13 in the optimized model-NSP13ATPMg.2+ -RNA and model-NSP13-ADPMg.2+ -RNA. NSP13’s residues 283, 284, 285, 286, 287, 288, 289, 290, 375, 442, 443, and 540 bind ATP1003/ADP1003 and MG1004 in all the six optimized models. Rich MD-HBs and Opt-SBs are presented in this chapter. Keywords COVID-19 virus · RNA helicase (NSP13) · Binding with ADP-Mg.2+ , ATP-Mg.2+ , and RNA · Optimization and MD (molecular dynamics) studies · Basic structural bioinformatics
6.1 Introduction The SARS-CoV-2 nonstructural proteins (NSPs) coordinate genome 26 replication and gene expression. Structural analyses revealed the basis for coupling of the essential NSP13 helicase with the RNA-dependent RNA polymerase (RdRp), where the holo-RdRp and RNA substrate (the replication-transcription complex, or RTC) are associated with two copies of NSP13 (NSP13.2 -RTC). One copy of NSP13 interacts with the template RNA in an opposing polarity to the RdRp and is envisaged to drive the RdRp backward on the RNA template (backtracking [225]), prompting questions as to how the RdRp can efficiently synthesize RNA in the presence of NSP13. In [66] the authors use cryo-electron microscopy and MD simulations to analyze the NSP13.2 -RTC, revealing four distinct conformational states of the helicases, and their results suggest a mechanism for the NSP13.2 -RTC to © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_6
243
244
6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA
turn backtracking on and off, using an allosteric mechanism to switch between RNA synthesis and backtracking in response to stimuli at the RdRp active site [66]. In this chapter, we will study the NSP13 in complex with ADP-Mg.2+ , ATP-Mg.2+ , and RNA from optimization and MD point of view; some basic structural bioinformatics such as HBs, SBs, RMSF, etc. will be presented.
6.2 Materials and Methods Two sets of MD simulation trajectories of the SARS-CoV-2 helicase NSP13 were gotten from the openly online accessible website [321]. These trajectories are described in [66]. Set 1 contains 12 5 .μs simulation trajectories of NSP13 bound to various substrates starting from the ATPMg.2+ —and RNA-bound conformation; in trajectories [12970406, 12970408, 12970412] NSP13 was bound to ATPMg.2+ and RNA; in trajectories [12258863, 12258865, 12251869] NSP13 was bound to ADPMg.2+ and RNA; in trajectories [12258868, 12257092, 12259873] NSP13 was bound to ATPMg.2+ ; and in trajectories [12257049, 12251866, 12251868] NSP13 was bound to ADPMg.2+ . Set 2 contains ten 25 .μs simulation trajectories of NSP13 bound to ADPMg.2+ ; trajectories [12212701, 12212688, 12212691, 12212689, 12212693] started from the NSP13.1-open conformation and trajectories [12225252, 12225258, 12225255, 12225240, 12225249] started from the NSP13.1closed conformation. We optimized the structures of the six models (model-NSP13-ATPMg.2+ -RNA, model-NSP13-ADPMg.2+ -RNA, model-NSP13.1-open-ADPMg.2+ , model-NSP13ATPMg.2+ , model-NSP13-ADPMg.2+ , and model-NSP13.1-close-ADPMg.2+ ), and got some basic structural bioinformatics (such as HBs, SBs, PIs, and HYDs) about the optimized six models and then confirmed these basic bioinformatics by the MD simulation trajectories [12970406, 12970408, 12970412; 12258863, 12258865, 12251869; 12258868, 12257092, 12259873; 12257049, 12251866, 12251868; 12212701, 12212688, 12212691, 12212689, 12212693; 12225252, 12225258, 12225255, 12225240, 12225249] of [321].
6.3 New Results and Discussions We optimized the following six models (Fig. 6.1): model-NSP13-ATPMg.2+ -RNA, model-NSP13-ADPMg.2+ -RNA, model-NSP13.1-open-ADPMg.2+ , model-NSP13ATPMg.2+ , model-NSP13-ADPMg.2+ , and model-NSP13.1-close-ADPMg.2+ . The RMSD values between the optimized and unoptimized models are 2.735522 Å, 1.665655 Å, 7.605859 Å, respectively, for NSP13-ATPMg.2+ -RNA/NSP13ADPMg.2+ -RNA, NSP13-ATPMg.2+ /NSP13-ADPMg.2+ , open / close models. The optimized six models are shown in Fig. 6.1 and their residues’ numbers binding with ATP1003/ADP1003 and MG1004 are listed in Table 6.1 and shown in Fig. 6.2.
6.3 New Results and Discussions
245
Fig. 6.1 3D structures of the six optimized models of model-NSP13-ATPMg.2+ -RNA, modelNSP13-ADPMg.2+ -RNA, model-NSP13.1-open-ADPMg.2+ , model-NSP13-ATPMg.2+ , modelNSP13-ADPMg.2+ , and model-NSP13.1-close-ADPMg.2+
Fig. 6.2 The ligand ATP1003/ADP1003 and MG1004 interaction diagram of each optimized model
Figure 6.3 shows the Poisson-Boltzmann electrostatic potential surface (EPS) charges’ distributions of the optimized NSP13.1-open-ADPMg.2+ 5-1_12212701 model and the optimized NSP13.1-close-ADPMg.2+ 6-1_12225252 model, where we might see that the close model has more positive EPS than the open model. Table 6.2 lists all the SBs of the optimized models of NSP13-ATPMg.2+ -RNA, NSP13-ADPMg.2+ -RNA, NSP13-ATPMg.2+ , and NSP13-ADPMg.2+ , and Table 6.3 lists all the SBs of the optimized models of NSP13.1-open-ADPMg.2+ and NSP13.1close-ADPMg.2+ . Tables 6.4, 6.5, 6.6, 6.7, 6.8 and 6.9 present some stronger
246
6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA
Fig. 6.3 The Poisson-Boltzmann electrostatic potential surface charges’ distributions of the optimized NSP13.1-open-ADPMg.2+ 5-1_12212701 model and the optimized NSP13.1-closeADPMg.2+ 6-1_12225252 model
HBs during MDs’ rep1-rep3 of model-NSP13-ATPMg.2+ -RNA, model-NSP13ADPMg.2+ -RNA, model-NSP13-ATPMg.2+ , model-NSP13-ADPMg.2+ , and rep1rep5 of model-NSP13.1-open-ADPMg.2+ and model-NSP13.1-close-ADPMg.2+ ; Table 6.10 shows that the segment ASN51-GLY91 of NSP13 has large RMSF values during all the MDs. Figures 6.4 and 6.5 show the RNA-6CCCAUGUG13 binding with NSP13ATP-Mg.2+ in the optimized NSP13-ATPMg.2+ -RNA model and the RNA6CCCAUGUG13 binding with NSP13-ADP-Mg.2+ in the optimized NSP13ADPMg.2+ -RNA model, respectively. Table 6.11 lists NSP13’s residue binding with RNA-6CCCAUGUG13 of each optimized model.
6.4 Concluding Remarks This chapter studied the six models of model-NSP13-ATPMg.2+ -RNA, modelNSP13-ADPMg.2+ -RNA, model-NSP13-ATPMg.2+ , model-NSP13-ADPMg.2+ , model-NSP13.1-open-ADPMg.2+ , and model-NSP13.1-close-ADPMg.2+ by the use of optimization and MD technologies. NSP13’s segments such as ASN51GLY91, 151–221, 471–531, and 441/461/481/541/551–581 have larger root mean
6.4 Concluding Remarks
247
Fig. 6.4 RNA-6CCCAUGUG13 binding with NSP13-ATP-Mg.2+ in the optimized NSP13ATPMg.2+ -RNA model
Fig. 6.5 RNA-6CCCAUGUG13 binding with NSP13-ADP-Mg.2+ in the optimized NSP13ADPMg.2+ -RNA model
square fluctuations during MDs. NSP13’s residues 139, 142, 177, 179, 180, 230, 231, 311, 337, 361, 382, 383, 390, 408, 409, 410, 485, 486, 514, 515, 516, 532, 534, 535, and 554 bind RNA-6CCCAUGUG13 in the optimized model-NSP13ATPMg.2+ -RNA and model-NSP13-ADPMg.2+ -RNA. NSP13’s residues 283, 284, 285, 286, 287, 288, 289, 290, 375, 442, 443, and 540 bind ATP1003/ADP1003 and MG1004 in all the six optimized models. Rich MD-HBs and Opt-SBs are presented in this chapter.
NSP13.1-close-ADPMg.2+
NSP13.1-open-ADPMg.2+
NSP13-ADPMg.2+
NSP13-ATPMg.2+
NSP13-ADPMg.2+ -RNA
NSP13-ATPMg.2+ -RNA
261, 264, 283, 284, 265, 285, 286, 287, 288, 289, 290, 319, 320, 323, 324, 374, 375, 442, 443, 465, 538, 540, 567, 569, ADP1003, MG1004 261, 264, 265, 283, 284, 285, 286, 287, 288, 289, 290, 319, 320, 323, 324, 374, 375, 442, 443, 465, 538, 540, 567, 569, ADP1003, MG1004 261, 264, 265, 283, 284, 285, 286, 287, 288, 289, 290, 319, 320, 323, 324, 374, 375, 442, 443, 465, 538, 540, 567, 569, ADP1003, MG1004 261, 264, 265, 283, 284, 285, 286, 287, 288, 289, 290, 319, 320, 323, 324, 374, 375, 442, 443, 465, 538, 540, 567, 569, ADP1003, MG1004
6-4_12225240
6-5_12225249
261, 264, 265, 283, 284, 285, 286, 287, 288, 289, 290, 320, 374, 375, 442, 443, 540, MG1004
6-3_12225255
261, 264, 265, 283, 284, 285, 286, 287, 288, 289, 290, 320, 374, 375, 442, 443, 540, MG1004
5-5_12212693
261, 264, 265, 283, 284, 285, 286, 287, 288, 289, 290, 319, 320, 323, 324, 374, 375, 442, 443, 465, 538, 540, 567, 569, ADP1003, MG1004
261, 264, 265, 283, 284, 285, 286, 287, 288, 289, 290, 320, 374, 375, 442, 443, 540, MG1004
5-4_12212689
6-2_12225258
261, 264, 265, 283, 284, 285, 286, 287, 288, 289, 290, 320, 374, 375, 442, 443, 540, MG1004
5-3_12212691
6-1_12225252
261, 264, 265, 283, 284, 285, 286, 287, 288, 289, 290, 320, 374, 375, 442, 443, 540, MG1004
261, 262, 283, 284, 285, 286, 287, 288, 289, 290, 319, 320, 323, 324, 375, 440, 441, 442, 443, 465, 538, 540, 569, ADP1003, MG1004
5-2_12212688
261, 262, 283, 284, 285, 286, 287, 288, 289, 290, 319, 320, 323, 324, 375, 440, 441, 442, 443, 465, 538, 540, 569, ADP1003, MG1004
4-3_12251868
5-1_12212701
261, 262, 283, 284, 285, 286, 287, 288, 289, 290, 319, 320, 323, 324, 375, 440, 441, 442, 443, 465, 538, 540, 569, ADP1003, MG1004
261, 283, 284, 285, 286, 287, 288, 289, 290, 320, 323, 375, 440, 441, 442, 443, 465, 537, 538, 540, 567, 569, ATP1003, MG1004
4-2_12251866
261, 283, 284, 285, 286, 287, 288, 289, 290, 320, 323, 375, 440, 441, 442, 443, 465, 537, 538, 540, 567, 569, ATP1003, MG1004
3-3_12259873
4-1_12257049
261, 283, 284, 285, 286, 287, 288, 289, 290, 320, 323, 375, 440, 441, 442, 443, 465, 537, 538, 540, 567, 569, ATP1003, MG1004
261, 262, 283, 284, 285, 286, 287, 288, 289, 290, 375, 442, 443, 538, 540, ADP1003, MG1004
3-2_12257092
261, 262, 283, 284, 285, 286, 287, 288, 289, 290, 375, 442, 443, 538, 540, ADP1003, MG1004
2-3_12251869
3-1_12258868
261, 262, 283, 284, 285, 286, 287, 288, 289, 290, 375, 442, 443, 538, 540, ADP1003, MG1004
283, 284, 285, 286, 287, 288, 289, 290, 320, 323, 375, 404, 442, 443, 540, 567, 569, ATP1003, MG1004
1-3_12970412
2-2_12258865
283, 284, 285, 286, 287, 288, 289, 290, 320, 323, 375, 404, 442, 443, 540, 567, 569, ATP1003, MG1004
1-2_12970408
2-1_12258863
261, 283, 284, 285, 286, 287, 288, 289, 290, 320, 324, 375, 442, 443, 540, ATP1003, MG1004
1-1_12970406
Table 6.1 The NSP13’s residues binding with ATP1003/ADP1003, MG1004 of each optimized model
248 6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA
6.4 Concluding Remarks
249
Table 6.2 The SBs of the optimized models of NSP13-ATPMg.2+ -RNA, NSP13-ADPMg.2+ RNA, NSP13-ATPMg.2+ , and NSP13-ADPMg.2+ 1_NSP13-ATPMg2+-RNA
1_NSP13-ATPMg2+-RNA
2_NSP13-ADPMg2+-RNA
3_NSP13-ATPMg2+
4_NSP13-ADPMg2+
seed1
seed2-seed3
seed1-seed3
seed1-seed3
seed1-seed3
ASP204-ARG490
ASP204-ARG490
ASP204-ARG490
ASP113-LYS414
ASP113-LYS414
ASP207-ARG155
ASP207-ARG173
ASP315-ARG332
ASP204-ARG490
ASP160-LYS218
ASP315-ARG332
ASP315-ARG332
ASP458-LYS460
ASP204-LYS524
ASP204-ARG490
ASP344-LYS345
ASP369-ARG303
ASP483-LYS202
ASP207-ARG173
ASP315-ARG332
ASP369-LYS394
ASP383-ARG409
ASP534-ARG560
ASP315-ARG332
ASP344-LYS345
ASP483-ARG173
ASP435-LYS271
ASP542-LYS569
ASP344-LYS345
ASP369-LYS394
GLU136-ARG21
ASP534-ARG560
GLU128-LYS131
ASP369-LYS394
ASP383-LYS139
GLU142-ARG409
ASP542-LYS569
GLU136-ARG21
ASP435-LYS271
ASP435-LYS271
GLU143-LYS146
ASP580-ARG579
GLU142-LYS139
ASP450-LYS467
ASP534-ARG560
GLU168-LYS171
GLU136-ARG21
GLU143-LYS139
ASP458-LYS460
ASP542-LYS569
GLU201-ARG178
GLU143-LYS146
GLU143-LYS146
ASP483-LYS202
ASP580-LYS584
GLU261-ARG442
GLU201-ARG178
GLU197-ARG337
ASP542-LYS569
ASP583-ARG579
GLU353-LYS347
GLU244-LYS276
GLU319-LYS320
ASP580-LYS584
GLU128-LYS131
GLU365-ARG392
GLU353-LYS347
GLU353-LYS347
ASP583-ARG579
GLU136-ARG21
GLU540-LYS569
GLU418-LYS430
GLU375-LYS288
ASP583-LYS584
GLU143-HIS230
GLU420-ARG427
GLU447-LYS467
GLU128-LYS131
GLU143-LYS146
GLU420-LYS430
GLU498-ARG502
GLU136-ARG21
GLU156-HIS164
GLU498-ARG502
GLU540-ARG443
GLU143-HIS230
GLU168-LYS171
GLU540-ARG443
GLU540-LYS320
GLU143-LYS139
GLU197-ARG337
GLU551-LYS477
GLU143-LYS146
GLU201-ARG212
GLU168-LYS171
GLU201-LYS524
GLU197-ARG337
GLU244-LYS276
GLU201-ARG212
GLU261-LYS323
GLU244-LYS276
GLU319-LYS320
GLU261-LYS323
GLU353-LYS347
GLU353-LYS347
GLU365-ARG392
GLU365-ARG390
GLU375-LYS288
GLU498-ARG497
GLU420-LYS430
GLU540-ARG443
GLU498-ARG502
GLU540-LYS320
GLU540-ARG443
GLU551-LYS477
GLU540-LYS320 GLU540-LYS569 GLU551-LYS477
250 Table 6.3 The SBs of the optimized models of NSP13.1-open-ADPMg.2+ and NSP13.1-close-ADPMg.2+
6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA NSP13.1-open-ADPMg.2+
NSP13.1-close-ADPMg.2+
seed1-seed5
seed1-seed5
ASP113-LYS414
ASP113-LYS414
ASP160-LYS218
ASP204-ARG490
ASP207-ARG173
ASP207-ARG173
ASP315-ARG332
ASP223-ARG186
ASP328-LYS329
ASP315-ARG332
ASP328-LYS347
ASP369-LYS394
ASP32-LYS28
ASP450-LYS467
ASP344-ARG339
ASP458-LYS460
ASP369-LYS394
ASP483-ARG173
ASP450-LYS462
ASP534-ARG560
ASP483-ARG490
ASP542-LYS569
ASP534-ARG560
ASP56-HIS75
ASP542-LYS508
ASP580-LYS584
ASP542-LYS569
ASP583-ARG579
ASP583-ARG579
ASP59-LYS40
GLU128-LYS131
GLU128-ARG427
GLU136-ARG21
GLU128-LYS131
GLU142-ARG409
GLU136-ARG21
GLU142-LYS139
GLU142-LYS139
GLU143-LYS139
GLU143-LYS139
GLU143-LYS146
GLU143-LYS146
GLU156-ARG155
GLU156-HIS164
GLU156-HIS164
GLU168-LYS171
GLU162-ARG161
GLU197-ARG337
GLU168-LYS171
GLU197-ARG339
GLU197-ARG22
GLU201-ARG212
GLU201-ARG178
GLU244-LYS276
GLU201-ARG212
GLU261-LYS323
GLU244-LYS276
GLU319-LYS569
GLU319-LYS569
GLU341-ARG178
GLU341-HIS311
GLU353-LYS347
GLU353-LYS329
GLU365-ARG390
GLU353-LYS347
GLU420-LYS430
GLU365-ARG390
GLU498-ARG497
GLU375-LYS288
GLU540-ARG443
GLU420-LYS430
GLU540-LYS320
GLU447-LYS467
GLU551-LYS477
GLU498-ARG502 GLU540-ARG443 GLU540-LYS320
6.4 Concluding Remarks
251
Table 6.4 Stronger HBs during MDs’ rep1-rep3 of model-NSP13-ATPMg.2+ -RNA 1_NSP13-ATPMg2+-RNA 1-1_12970406
1-2_12970408
1-3_12970412
THR12.OG1-LEU25.O 78.10%
SER289.OG-ASP374.OD2 78.10%
SER513.OG-ASN519.OD1 75.24%
SER289.OG-ASP374.OD2 68.57%
SER513.OG-ASN519.OD1 64.76%
THR12.OG1-LEU25.O 74.29%
TYR120.OH-TRP114.O 66.67%
ASN489.N-GLN518.OE1 61.90%
THR286.OG1-PRO283.O 62.86%
THR141.OG1-THR137.O 65.71%
TYR306.N-VAL356.O 61.90%
SER289.OG-ASP374.OD1 62.86%
TYR185.N-TYR224.O 61.90%
THR451.OG1-GLU447.O 60.95%
THR451.OG1-GLU447.O 62.86%
TYR306.OH-ALA292.O 60.00%
THR141.OG1-THR137.O 60.00%
SER229.OG-GLU143.O 61.90%
LEU65.N-PHE81.O 60.00%
THR380.OG1-ASP383.OD2 59.05%
THR141.OG1-THR137.O 59.05%
CYM5.N-SER10.O 60.00%
CYS441.N-LYS462.O 58.10%
TYR306.N-VAL356.O 59.05%
THR451.OG1-GLU447.O 58.10%
TYR306.OH-ALA292.O 57.14%
PHE546.N-LEU573.O 58.10%
THR144.OG1-ALA140.O 57.14%
SER80.OG-PRO77.O 57.14%
CYS441.N-LYS462.O 57.14%
SER331.OG-SER350.O 56.19%
PHE472.N-ILE572.O 56.19%
PHE373.N-VAL397.O 57.14%
THR111.OG1-ASN107.O 55.24%
TYR185.N-TYR224.O 55.24%
SER453.OG-VAL449.O 56.19%
SER513.OG-ASN519.OD1 55.24%
THR111.OG1-ASN107.O 55.24%
TYR64.N-TYR71.O 55.24%
SER536.OG-THR532.O 54.29%
LEU43.N-ARG15.O 54.29%
SER331.OG-SER350.O 54.29%
ARG443.NH1-THR566.O 54.29%
SER453.OG-VAL449.O 53.33%
ILE195.N-GLY184.O 54.29%
TYR306.N-VAL356.O 54.29%
LEU325.N-ALA321.O 53.33%
LEU25.N-LEU14.O 54.29%
THR125.OG1-ILE121.O 53.33%
THR12.OG1-LEU25.O 52.38%
TYR306.OH-ALA292.O 53.33%
PHE472.N-ILE572.O 53.33%
TYR198.N-PHE182.O 52.38%
VAL452.N-ILE448.O 52.38%
ASN388.ND2-PRO238.O 52.38%
TYR299.OH-TYR269.O 52.38%
ARG409.NH1-PRO408.O 52.38%
SER555.OG-THR552.OG1 50.48%
TYR120.OH-TRP114.O 51.43%
PHE511.N-PRO529.O 52.38%
ASP374.N-THR307.O 49.52%
PHE357.N-SER331.O 51.43%
GLY150.N-PRO172.O 52.38%
TYR515.OH-THR550.OG1 49.52%
THR286.OG1-PRO283.O 50.48%
TYR185.N-TYR224.O 52.38%
TYR198.N-PHE182.O 48.57%
SER385.OG-ALA237.O 50.48%
ASN489.N-GLN518.OE1 51.43%
SER80.OG-PRO77.O 47.62%
ILE488.N-THR481.O 49.52%
PHE357.N-SER331.O 50.48%
VAL372.N-VAL305.O 47.62%
MET429.N-VAL425.O 49.52%
ILE333.N-PHE357.O 50.48%
GLY184.N-GLY196.O 47.62%
PHE511.N-PRO529.O 49.52%
TYR198.OH-TYR217.O 50.48%
TYR71.N-TYR64.O 46.67%
ARG409.NH1-PRO408.O 47.62%
LEU43.N-ARG15.O 50.48%
PHE546.N-LEU573.O 46.67%
LEU65.N-PHE81.O 47.62%
THR144.OG1-ALA140.O 50.48%
SER385.OG-ALA237.O 45.71%
TYR64.N-TYR71.O 47.62%
THR111.OG1-ASN107.O 50.48%
ILE545.N-VAL510.O 45.71%
LEU25.N-LEU14.O 47.62%
ASN388.ND2-PRO238.O 49.52%
SER577.OG-TYR476.O 45.71%
ASN388.ND2-PRO238.O 47.62%
LEU65.N-PHE81.O 49.52%
THR550.OG1-SER555.OG 44.76%
VAL452.N-ILE448.O 46.67%
THR12.N-GLY3.O 48.57%
TYR246.N-MET274.O 44.76%
LEU165.N-ASP207.O 46.67%
PHE182.N-TYR198.O 48.57%
PHE182.N-TYR198.O 44.76%
PHE373.N-VAL397.O 46.67%
SER385.OG-ALA237.O 48.57%
ILE333.N-PHE357.O 44.76%
CYM5.N-SER10.O 45.71%
MET429.N-VAL425.O 47.62%
LEU325.N-ALA321.O 44.76%
PHE546.N-LEU573.O 45.71%
TYR198.N-PHE182.O 47.62%
TYR64.N-TYR71.O 43.81%
VAL209.N-LEU163.O 45.71%
GLY184.N-GLY196.O 47.62%
PHE357.N-SER331.O 43.81%
GLN518.NE2-ASN489.O 44.76%
VAL154.N-ASP223.O 47.62%
SER577.N-GLN548.OE1 43.81%
LEU500.N-VAL496.O 42.86%
THR413.N-THR115.O 46.67%
PHE511.N-PRO529.O 43.81%
THR481.N-ILE488.O 42.86%
TYR120.OH-TRP114.O 46.67%
SER453.OG-VAL449.O 42.86%
THR144.OG1-ALA140.O 42.86%
VAL372.N-VAL305.O 45.71%
ALA368.N-ARG392.O 42.86%
SER331.OG-SER350.O 42.86%
CYM5.N-SER10.O 45.71%
ASN381.ND2-ASN124.OD1 42.86%
ALA186.N-VAL193.O 42.86%
ASP374.N-THR307.O 45.71%
ARG560.NH1-ASP534.OD1 42.86%
ALA110.N-PHE106.O 42.86%
VAL210.N-GLU201.O 44.76%
ARG155.N-HID164.O 40.95%
ILE333.N-PHE357.O 41.90%
PHE472.N-ILE572.O 44.76%
VAL210.N-GLU201.O 40.95%
ILE195.N-GLY184.O 41.90%
TYR48.OH-PHE90.O 44.76%
ALA575.N-PHE546.O 40.95%
ILE334.N-ASN349.OD1 40.95%
GLN548.N-ALA575.O 44.76%
VAL193.N-ALA186.O 40.95%
HID164.N-GLU156.O 40.95%
CYS358.N-TYR306.O 42.86%
GLN243.NE2-TYR277.O 40.95%
PHE182.N-TYR198.O 40.95%
THR228.OG1-VAL181.O 42.86%
LEU83.N-LEU63.O 40.00%
ILE525.N-VAL521.O 40.95%
VAL232.N-ILE20.O 41.90%
THR37.OG1-HID33.O 40.00%
SER536.OG-THR532.O 40.00%
ALA186.N-VAL193.O 41.90%
ALA134.N-LEU130.O 40.00%
TYR476.N-MET576.O 40.00%
LEU280.N-TYR398.O 40.95%
LEU43.N-ARG15.O 40.00%
SER377.OG-ASP401.O 40.00%
VAL209.N-LEU163.O 40.95%
MET429.N-VAL425.O 39.05%
VAL210.N-GLU201.O 40.00%
ARG155.N-HID164.O 40.95%
VAL226.N-THR183.O 39.05%
GLY184.N-GLY196.O 40.00%
MET576.N-MET474.O 40.95%
ASN562.N-VAL558.O 39.05%
ASN489.ND2-LYS477.O 40.00%
TYR457.OH-ASP401.OD1 40.00%
TYR299.OH-TYR269.O 39.05%
TYR246.N-MET274.O 39.05%
THR125.OG1-ILE121.O 40.00%
LEU391.N-VAL387.O 39.05%
ARG303.N-ASP369.OD2 39.05%
ASN489.ND2-LYS477.O 40.00%
ASN349.N-ARG332.O 39.05%
VAL154.N-ASP223.O 39.05%
LEU163.N-VAL209.O 40.00%
GLN492.NE2-GLN548.O 38.10%
VAL372.N-VAL305.O 39.05%
CYS30.N-CYM26.O 40.00%
THR286.OG1-PRO283.O 38.10%
TYR149.OH-PHE145.O 39.05%
SER80.OG-PRO77.O 40.00%
SER166.N-THR153.O 37.14%
THR307.N-VAL372.O 39.05%
TYR541.N-ARG567.O 40.00%
PHE373.N-VAL397.O 37.14%
ASP374.N-THR307.O 38.10%
GLN492.NE2-GLN548.O 39.05%
(continued)
252
6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA
Table 6.4 (continued) 1_NSP13-ATPMg2+-RNA 1-1_12970406
1-2_12970408
1-3_12970412
ILE109.N-ASP105.O 37.14%
GLY150.N-PRO172.O 38.10%
TYR541.OH-GLN531.OE1 39.05%
THR199.N-ARG212.O 37.14%
THR431.OG1-ARG427.O 37.14%
LEU325.N-ALA321.O 39.05%
LEU138.N-ALA134.O 37.14%
ILE304.N-GLN354.O 37.14%
THR566.OG1-ASN562.O 39.05%
THR115.OG1-ASP113.OD2 37.14%
GLN548.N-ALA575.O 37.14%
SER377.OG-ASP401.O 38.10%
ILE195.N-GLY184.O 36.19%
THR501.OG1-ARG497.O 37.14%
GLN275.NE2-SER278.OG 38.10%
VAL154.N-ASP223.O 36.19%
LEU590.N-ALA473.O 36.19%
PHE90.N-LEU83.O 38.10%
THR566.OG1-ASN562.O 35.24%
ARG560.NH2-ASP534.OD2 36.19%
HID164.N-GLU156.O 38.10%
CYS441.N-LYS462.O 35.24%
TYR71.N-TYR64.O 36.19%
ILE304.N-GLN354.O 38.10%
Table 6.5 Stronger HBs during MDs’ rep1-rep3 of model-NSP13-ADPMg.2+ -RNA 2_NSP13-ADPMg2+-RNA 2-1_12258863
2-2_12258865
2-3_12251869
THR12.OG1-LEU25.O 70.48%
THR12.OG1-LEU25.O 68.57%
THR12.OG1-LEU25.O 79.05%
THR451.OG1-GLU447.O 65.71%
THR451.OG1-GLU447.O 65.71%
ASN489.N-GLN518.OE1 63.81%
THR566.OG1-ASN562.O 64.76%
TYR306.N-VAL356.O 62.86%
THR451.OG1-GLU447.O 63.81%
ASN489.N-GLN518.OE1 62.86%
TYR185.N-TYR224.O 61.90%
THR566.OG1-ASN562.O 62.86%
THR141.OG1-THR137.O 62.86%
SER513.OG-ASN519.OD1 60.95%
TYR541.OH-GLN531.OE1 61.90%
THR37.OG1-HID33.O 61.90%
THR141.OG1-THR137.O 60.00%
TYR306.OH-ALA292.O 61.90%
TYR185.N-TYR224.O 58.10%
TYR306.OH-ALA292.O 60.00%
SER513.OG-ASN519.OD1 60.00%
SER513.OG-ASN519.OD1 58.10%
THR125.OG1-ILE121.O 58.10%
TYR306.N-VAL356.O 59.05%
PHE182.N-TYR198.O 57.14%
TYR64.N-TYR71.O 56.19%
THR141.OG1-THR137.O 58.10%
TYR306.N-VAL356.O 56.19%
TYR120.OH-TRP114.O 53.33%
TYR185.N-TYR224.O 58.10%
ASN388.ND2-PRO238.O 54.29%
THR566.OG1-ASN562.O 51.43%
THR125.OG1-ILE121.O 57.14%
SER80.OG-PRO77.O 53.33%
PHE472.N-ILE572.O 51.43%
CYM5.N-SER10.O 57.14%
ILE545.N-VAL510.O 53.33%
SER331.OG-SER350.O 51.43%
ARG560.NH2-ASP534.OD2 56.19%
THR286.OG1-PRO283.O 53.33%
ASN388.ND2-PRO238.O 51.43%
ASP374.N-THR307.O 56.19%
CYM5.N-SER10.O 52.38%
VAL210.N-GLU201.O 50.48%
SER331.OG-SER350.O 54.29%
TYR306.OH-ALA292.O 52.38%
PHE373.N-VAL397.O 50.48%
ARG560.NH1-ASP534.OD1 54.29%
PHE357.N-SER331.O 51.43%
VAL154.N-ASP223.O 50.48%
ASN381.ND2-ASN124.OD1 54.29%
TYR299.OH-TYR269.O 51.43%
CYM5.N-SER10.O 49.52%
SER536.OG-VAL533.O 53.33%
TYR120.OH-TRP114.O 51.43%
SER453.OG-VAL449.O 48.57%
THR286.OG1-PRO283.O 52.38%
TYR48.OH-VAL42.O 51.43%
ASN489.N-GLN518.OE1 48.57%
TYR120.OH-TRP114.O 51.43%
ILE195.N-GLY184.O 50.48%
GLY184.N-GLY196.O 47.62%
MET576.N-MET474.O 49.52%
GLY66.N-SER69.O 50.48%
ASP374.N-THR307.O 47.62%
PHE357.N-SER331.O 49.52%
SER377.OG-ASP401.O 49.52%
LEU65.N-PHE81.O 47.62%
GLN492.NE2-TYR476.O 48.57%
TYR198.N-PHE182.O 49.52%
HID164.N-GLU156.O 47.62%
GLY184.N-GLY196.O 48.57%
SER385.OG-ALA237.O 49.52%
PHE511.N-PRO529.O 46.67%
PHE472.N-ILE572.O 48.57%
SER453.OG-VAL449.O 49.52%
SER536.OG-VAL533.O 46.67%
TYR198.N-PHE182.O 48.57%
THR144.OG1-ALA140.O 47.62%
TYR299.OH-TYR269.O 46.67%
LEU65.N-PHE81.O 47.62%
ILE333.N-PHE357.O 47.62%
PHE546.N-LEU573.O 45.71%
VAL210.N-GLU201.O 47.62%
SER331.OG-SER350.O 47.62%
SER577.OG-TYR476.O 45.71%
TYR299.OH-TYR269.O 47.62%
LEU65.N-PHE81.O 47.62%
ILE545.N-VAL510.O 44.76%
TYR457.OH-ASP401.OD1 47.62%
VAL452.N-ILE448.O 46.67%
TYR541.N-ARG567.O 44.76%
MET429.N-VAL425.O 47.62%
CYS441.N-LYS462.O 46.67%
CYS441.N-LYS462.O 44.76%
TYR541.N-ARG567.O 46.67%
CYS30.N-CYM26.O 45.71%
TYR457.OH-ASP401.OD1 44.76%
SER453.OG-VAL449.O 45.71%
PHE511.N-PRO529.O 45.71%
THR137.OG1-PHE133.O 43.81%
THR37.OG1-HID33.O 45.71%
VAL372.N-VAL305.O 45.71%
GLN243.NE2-TYR277.O 43.81%
CYS358.N-TYR306.O 45.71%
LEU43.N-ARG15.O 44.76%
TYR71.N-TYR64.O 43.81%
PHE546.N-LEU573.O 45.71%
PHE90.N-LEU83.O 44.76%
MET429.N-VAL425.O 43.81%
CYS441.N-LYS462.O 44.76%
SER166.N-THR153.O 44.76%
SER148.OG-THR144.O 43.81%
THR431.OG1-ARG427.O 43.81%
THR12.N-GLY3.O 44.76%
ASN562.N-VAL558.O 42.86%
SER80.OG-PRO77.O 43.81%
PHE546.N-LEU573.O 43.81%
ILE195.N-GLY184.O 42.86%
LEU138.N-ALA134.O 42.86%
THR125.OG1-ILE121.O 43.81%
VAL372.N-VAL305.O 42.86%
ILE333.N-PHE357.O 42.86%
LEU138.N-ALA134.O 43.81%
TYR198.N-PHE182.O 42.86%
GLN243.NE2-TYR277.O 42.86%
LEU280.N-TYR398.O 43.81%
SER80.OG-PRO77.O 41.90%
HID164.N-GLU156.O 42.86%
GLN243.NE2-TYR277.O 43.81%
GLY3.N-THR12.O 41.90%
ASN388.ND2-PRO238.O 42.86%
LEU25.N-LEU14.O 43.81%
ILE512.N-ILE545.O 41.90%
TYR71.N-TYR64.O 41.90%
ASN349.N-ARG332.O 43.81%
THR431.OG1-ARG427.O 40.95%
VAL372.N-VAL305.O 41.90%
TYR64.N-TYR71.O 43.81%
THR12.N-GLY3.O 40.95%
LEU500.N-VAL496.O 40.95%
THR307.N-VAL372.O 43.81%
ALA186.N-VAL193.O 40.95%
THR144.OG1-ALA140.O 40.95%
TYR457.OH-ASP401.OD2 43.81%
CYS30.N-CYM26.O 40.00%
LEU43.N-ARG15.O 40.95%
(continued)
6.4 Concluding Remarks
253
Table 6.5 (continued) 2_NSP13-ADPMg2+-RNA 2-1_12258863
2-2_12258865
2-3_12251869
ALA186.N-VAL193.O 43.81%
ILE334.N-ASN349.OD1 40.00%
ALA575.N-PHE546.O 40.95%
LEU590.N-ALA473.O 42.86%
TYR457.OH-ASP401.OD2 40.00%
ALA186.N-VAL193.O 40.95%
GLY184.N-GLY196.O 42.86%
THR549.OG1-ALA487.O 40.00%
THR61.OG1-ASP59.OD2 40.95%
ASP374.N-THR307.O 42.86%
LEU43.N-ARG15.O 39.05%
LEU325.N-ALA321.O 40.95%
ILE304.N-GLN354.O 42.86%
GLY150.N-PRO172.O 39.05%
THR137.OG1-PHE133.O 40.95%
HID164.N-GLU156.O 42.86%
PHE182.N-TYR198.O 39.05%
PHE511.N-PRO529.O 40.00%
PHE472.N-ILE572.O 42.86%
SER577.N-GLN548.OE1 39.05%
VAL452.N-ILE448.O 40.00%
VAL154.N-ASP223.O 42.86%
ASN349.N-ARG332.O 38.10%
ALA368.N-ARG392.O 40.00%
TYR476.N-MET576.O 42.86%
CYS426.N-ASN423.OD1 37.14%
PHE182.N-TYR198.O 39.05%
TYR70.OH-GLY91.O 42.86%
ARG303.N-ASP369.OD1 37.14%
ILE334.N-ASN349.OD1 39.05%
THR137.OG1-PHE133.O 41.90%
ALA368.N-ARG392.O 37.14%
CYS30.N-CYM26.O 39.05%
LEU325.N-ALA321.O 41.90%
VAL193.N-ALA186.O 37.14%
THR12.N-GLY3.O 39.05%
TYR382.OH-MET233.O 41.90%
SER377.OG-LEU405.O 37.14%
GLN548.NE2-SER555.O 39.05%
THR153.N-SER166.O 41.90%
TYR246.N-MET274.O 37.14%
THR307.N-VAL372.O 39.05%
THR199.N-ARG212.O 41.90%
LEU590.N-ALA473.O 36.19%
LYS131.N-THR127.O 39.05%
ALA368.N-ARG392.O 41.90%
LEU325.N-ALA321.O 36.19%
GLY3.N-THR12.O 39.05%
ALA575.N-PHE546.O 40.95%
TYR541.OH-GLN531.OE1 36.19%
ILE512.N-ILE545.O 38.10%
VAL209.N-LEU163.O 40.95%
THR286.OG1-PRO283.O 36.19%
SER424.OG-ASN381.OD1 38.10%
THR61.OG1-ASP59.OD2 40.95%
THR307.OG1-CYS358.O 36.19%
LEU384.N-THR380.O 38.10%
THR111.OG1-ASN107.O 40.95%
ASN423.ND2-ALA379.O 35.24%
ARG155.N-HID164.O 38.10%
TYR71.N-TYR64.O 40.00%
ASP450.N-ALA446.O 35.24%
SER166.N-THR153.O 37.14%
ILE512.N-ILE545.O 40.00%
PHE357.N-SER331.O 35.24%
TYR64.N-TYR71.O 37.14%
Table 6.6 Stronger HBs during MDs’ rep1-rep3 of model-NSP13-ATPMg.2+ 3_NSP13-ATPMg2+ 3-1_12258868
3-2_12257092
3-3_12259873
THR12.OG1-LEU25.O 72.38%
THR12.OG1-LEU25.O 70.48%
THR12.OG1-LEU25.O 76.19%
SER513.OG-ASN519.OD1 70.48%
THR451.OG1-GLU447.O 68.57%
THR451.OG1-GLU447.O 71.43%
THR451.OG1-GLU447.O 64.76%
ASN489.N-GLN518.OE1 66.67%
ASN489.N-GLN518.OE1 69.52%
TYR306.N-VAL356.O 63.81%
TYR306.OH-ALA292.O 65.71%
SER513.OG-ASN519.OD1 66.67%
THR141.OG1-THR137.O 61.90%
THR125.OG1-ILE121.O 65.71%
TYR306.OH-ALA292.O 64.76%
SER331.OG-SER350.O 61.90%
TYR299.OH-TYR269.O 63.81%
TYR306.N-VAL356.O 62.86%
ASN489.N-GLN518.OE1 61.90%
SER513.OG-ASN519.OD1 60.95%
MET576.N-MET474.O 61.90%
TYR120.OH-TRP114.O 60.95%
THR141.OG1-THR137.O 60.95%
THR111.OG1-ASN107.O 60.95%
PHE472.N-ILE572.O 59.05%
SER331.OG-SER350.O 60.95%
GLN492.NE2-TYR476.O 60.95%
THR125.OG1-ILE121.O 58.10%
THR144.OG1-ALA140.O 58.10%
THR286.OG1-PRO283.O 59.05%
THR144.OG1-ALA140.O 58.10%
TYR306.N-VAL356.O 56.19%
ASP315.N-HID311.O 58.10%
TYR185.N-TYR224.O 57.14%
VAL154.N-ASP223.O 56.19%
VAL210.N-GLU201.O 57.14%
THR137.OG1-PHE133.O 56.19%
THR286.OG1-PRO283.O 55.24%
SER331.OG-SER350.O 57.14%
THR566.OG1-ASN562.O 55.24%
CYM5.N-SER10.O 55.24%
SER385.OG-ASN381.O 57.14%
TYR306.OH-ALA292.O 55.24%
TYR120.OH-TRP114.O 54.29%
THR37.OG1-ASP32.O 57.14%
THR286.OG1-PRO283.O 52.38%
TYR185.N-TYR224.O 54.29%
PHE511.N-PRO529.O 55.24%
VAL154.N-ASP223.O 52.38%
GLN492.NE2-TYR476.O 53.33%
GLY184.N-GLY196.O 55.24%
SER80.OG-PRO77.O 51.43%
THR431.OG1-ARG427.O 53.33%
TYR198.N-PHE182.O 54.29%
THR111.OG1-ASN107.O 50.48%
ILE333.N-PHE357.O 53.33%
TYR185.N-TYR224.O 53.33%
ASP374.N-THR307.O 50.48%
PHE511.N-PRO529.O 52.38%
THR566.OG1-ASN562.O 52.38%
TYR299.OH-TYR269.O 50.48%
ASN381.ND2-ASN124.OD1 52.38%
THR144.OG1-ALA140.O 52.38%
GLY184.N-GLY196.O 49.52%
ALA575.N-PHE546.O 52.38%
LEU43.N-ARG15.O 52.38%
ASN388.ND2-PRO238.O 49.52%
PHE472.N-ILE572.O 51.43%
PHE472.N-ILE572.O 51.43%
HID164.N-GLU156.O 47.62%
ALA134.N-LEU130.O 51.43%
PHE357.N-SER331.O 51.43%
TYR541.N-ARG567.O 46.67%
THR566.OG1-ASN562.O 50.48%
GLN243.NE2-TYR277.O 51.43%
GLN492.NE2-TYR476.O 46.67%
LEU43.N-ARG15.O 50.48%
PHE373.N-VAL397.O 50.48%
TYR64.N-TYR71.O 46.67%
SER80.OG-PRO77.O 49.52%
MET429.N-VAL425.O 48.57%
PHE511.N-PRO529.O 46.67%
THR111.OG1-ASN107.O 49.52%
HID164.N-GLU156.O 48.57%
THR183.N-VAL226.O 45.71%
ASN388.ND2-PRO238.O 49.52%
VAL154.N-ASP223.O 47.62%
THR431.OG1-ARG427.O 45.71%
GLY184.N-GLY196.O 49.52%
ASP374.N-THR307.O 47.62%
PHE357.N-SER331.O 45.71%
TYR198.N-PHE182.O 48.57%
THR481.N-ILE488.O 47.62%
SER453.OG-VAL449.O 45.71%
LEU325.N-ALA321.O 48.57%
TYR541.N-ARG567.O 47.62%
(continued)
254
6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA
Table 6.6 (continued) 3_NSP13-ATPMg2+ 3-1_12258868
3-2_12257092
3-3_12259873
TYR198.N-PHE182.O 44.76%
GLN243.NE2-TYR277.O 47.62%
THR125.OG1-ILE121.O 47.62%
TYR71.N-TYR64.O 44.76%
PHE546.N-LEU573.O 47.62%
LEU25.N-LEU14.O 46.67%
PHE546.N-LEU573.O 44.76%
SER453.OG-VAL449.O 46.67%
ASN388.ND2-PRO238.O 45.71%
GLU142.N-LEU138.O 43.81%
SER385.OG-ALA237.O 46.67%
CYS441.N-LYS462.O 45.71%
TYR543.OH-GLN470.OE1 43.81%
TYR71.N-TYR64.O 46.67%
THR137.OG1-PHE133.O 44.76%
ALA134.N-LEU130.O 43.81%
CYS441.N-LYS462.O 46.67%
SER80.OG-PRO77.O 44.76%
LEU325.N-ALA321.O 43.81%
HID164.N-GLU156.O 45.71%
THR431.OG1-ARG427.O 43.81%
LEU25.N-LEU14.O 43.81%
GLY150.N-PRO172.O 44.76%
TYR64.N-TYR71.O 43.81%
ARG332.N-LYS347.O 42.86%
ASN423.ND2-ALA379.O 44.76%
LEU325.N-ALA321.O 43.81%
ARG303.N-ASP369.OD1 42.86%
SER166.N-THR153.O 44.76%
TYR299.OH-TYR269.O 42.86%
ALA368.N-ARG392.O 42.86%
LEU65.N-PHE81.O 44.76%
VAL452.N-ILE448.O 42.86%
MET576.N-MET474.O 42.86%
MET576.N-MET474.O 44.76%
ILE195.N-GLY184.O 41.90%
ALA575.N-PHE546.O 42.86%
ILE545.N-VAL510.O 43.81%
VAL372.N-VAL305.O 41.90%
CYS441.N-LYS462.O 41.90%
THR199.N-ARG212.O 43.81%
LEU65.N-PHE81.O 41.90%
SER289.OG-ASP374.OD1 41.90%
ALA186.N-VAL193.O 43.81%
THR12.N-GLY3.O 41.90%
LEU65.N-PHE81.O 41.90%
TYR198.OH-TYR217.O 43.81%
TYR71.N-TYR64.O 41.90%
ALA186.N-VAL193.O 41.90%
THR137.OG1-PHE133.O 43.81%
THR153.N-SER166.O 41.90%
MET429.N-VAL425.O 41.90%
VAL210.N-GLU201.O 42.86%
SER453.OG-VAL449.O 40.95%
CYS426.N-ASN423.OD1 40.95%
PHE373.N-VAL397.O 42.86%
ILE376.N-ILE399.O 40.95%
GLN354.NE2-ALA302.O 40.95%
SER289.OG-ASP374.OD2 42.86%
ALA368.N-ARG392.O 40.95%
VAL210.N-GLU201.O 40.95%
ILE376.N-ILE399.O 41.90%
THR380.OG1-ASP383.OD1 40.95%
SER166.N-THR153.O 40.00%
ILE195.N-GLY184.O 40.95%
THR141.OG1-THR137.O 40.00%
GLN243.NE2-TYR277.O 40.00%
MET429.N-VAL425.O 40.95%
ILE333.N-PHE357.O 40.00%
ILE304.N-GLN354.O 40.00%
LEU138.N-ALA134.O 40.95%
ARG303.N-ASP369.OD2 40.00%
CYM5.N-SER10.O 40.00%
PHE357.N-SER331.O 40.95%
GLN354.NE2-ALA302.O 40.00%
ILE195.N-GLY184.O 40.00%
GLU143.N-LYS139.O 40.95%
TYR543.OH-GLN470.OE1 40.00%
LEU43.N-ARG15.O 39.05%
ASP374.N-THR307.O 40.95%
ALA575.N-PHE546.O 39.05%
THR380.OG1-ASP383.OD1 39.05%
TYR48.OH-VAL42.O 40.00%
CYM5.N-SER10.O 39.05%
ASN489.ND2-LYS477.O 39.05%
CYS30.N-CYM26.O 40.00%
ASN489.ND2-THR549.O 39.05%
TYR211.N-ALA161.O 39.05%
TYR64.N-TYR71.O 40.00%
PHE546.N-LEU573.O 39.05%
GLU201.N-VAL210.O 38.10%
ILE488.N-THR481.O 39.05%
GLY150.N-PRO172.O 39.05%
THR37.OG1-HID33.O 37.14%
ARG303.N-ASP369.OD1 39.05%
ILE304.N-GLN354.O 38.10%
SER385.OG-ALA237.O 37.14%
THR153.N-SER166.O 38.10%
ILE525.N-VAL521.O 37.14%
VAL372.N-VAL305.O 37.14%
ILE304.N-GLN354.O 38.10%
TYR211.N-ALA161.O 37.14%
THR199.N-ARG212.O 37.14%
TYR543.OH-GLN470.OE1 38.10%
SER536.OG-THR532.O 37.14%
SER555.OG-THR550.OG1 36.19%
ILE334.N-ASN349.OD1 37.14%
VAL209.N-LEU163.O 37.14%
ASN381.ND2-ASN124.OD1 36.19%
TYR246.N-MET274.O 37.14%
PHE182.N-TYR198.O 37.14%
ILE512.N-ILE545.O 36.19%
THR501.OG1-ARG497.O 37.14%
VAL193.N-ALA186.O 37.14%
GLY150.N-PRO172.O 36.19%
PHE90.N-LEU83.O 37.14%
TYR382.OH-MET233.O 37.14%
Table 6.7 Stronger HBs during MDs’ rep1-rep3 of model-NSP13-ADPMg.2+ 4_NSP13-ADPMg2+ 4-1_12257049
4-2_12251866
4-3_12251868
ASN489.N-GLN518.OE1 71.43%
THR12.OG1-LEU25.O 80.00%
THR141.OG1-THR137.O 67.62%
THR12.OG1-LEU25.O 68.57%
SER331.OG-SER350.O 66.67%
THR451.OG1-GLU447.O 66.67%
TYR306.N-VAL356.O 66.67%
THR451.OG1-GLU447.O 62.86%
THR12.OG1-LEU25.O 66.67%
THR141.OG1-THR137.O 65.71%
TYR306.OH-ALA292.O 62.86%
SER513.OG-ASN519.OD1 65.71%
THR451.OG1-GLU447.O 61.90%
THR141.OG1-THR137.O 59.05%
ASN489.N-GLN518.OE1 59.05%
SER513.OG-ASN519.OD1 59.05%
THR125.OG1-ILE121.O 59.05%
TYR120.OH-TRP114.O 58.10%
TYR48.OH-PHE90.O 57.14%
ALA407.N-LEU417.O 59.05%
VAL154.N-ASP223.O 58.10%
TYR541.OH-GLN531.OE1 57.14%
TYR306.N-VAL356.O 57.14%
THR566.OG1-ASN562.O 57.14%
(continued)
6.4 Concluding Remarks
255
Table 6.7 (continued) 4_NSP13-ADPMg2+ 4-1_12257049
4-2_12251866
4-3_12251868
SER331.OG-SER350.O 55.24%
SER536.OG-THR532.O 56.19%
THR125.OG1-ILE121.O 56.19%
TYR185.N-TYR224.O 54.29%
VAL210.N-GLU201.O 54.29%
THR144.OG1-ALA140.O 55.24%
PHE472.N-ILE572.O 54.29%
THR111.OG1-ASN107.O 54.29%
GLY184.N-GLY196.O 55.24%
TYR457.OH-ASP401.OD2 54.29%
TYR185.N-TYR224.O 53.33%
TYR185.N-TYR224.O 54.29%
TYR120.OH-TRP114.O 53.33%
CYS30.N-CYM26.O 52.38%
TYR198.N-PHE182.O 54.29%
THR566.OG1-ASN562.O 52.38%
THR566.OG1-ASN562.O 51.43%
TYR306.N-VAL356.O 54.29%
TYR306.OH-ALA292.O 52.38%
ASN388.ND2-PRO238.O 50.48%
TYR306.OH-ALA292.O 53.33%
LEU65.N-PHE81.O 52.38%
GLY150.N-PRO172.O 49.52%
ASN388.ND2-PRO238.O 53.33%
THR144.OG1-ALA140.O 50.48%
GLY184.N-GLY196.O 49.52%
THR286.OG1-PRO283.O 53.33%
GLN492.NE2-TYR476.O 50.48%
THR144.OG1-ALA140.O 46.67%
ALA575.N-PHE546.O 51.43%
ASN388.ND2-PRO238.O 49.52%
LEU138.N-ALA134.O 46.67%
CYM5.N-SER10.O 51.43%
LEU325.N-ALA321.O 49.52%
PHE357.N-SER331.O 46.67%
SER331.OG-SER350.O 51.43%
SER536.OG-VAL533.O 49.52%
PHE472.N-ILE572.O 46.67%
ASN381.ND2-ASN124.OD1 51.43%
VAL154.N-ASP223.O 48.57%
ILE545.N-VAL510.O 45.71%
ASP374.N-THR307.O 50.48%
THR125.OG1-ILE121.O 48.57%
SER453.OG-VAL449.O 45.71%
TYR299.OH-TYR269.O 50.48%
HID164.N-GLU156.O 47.62%
ILE512.N-ILE545.O 44.76%
THR199.N-ARG212.O 50.48%
PHE357.N-SER331.O 47.62%
ARG560.N-ASN557.OD1 44.76%
LEU43.N-ARG15.O 48.57%
LEU43.N-ARG15.O 47.62%
MET429.N-VAL425.O 44.76%
VAL210.N-GLU201.O 46.67%
TYR64.N-TYR71.O 47.62%
LYS131.N-THR127.O 43.81%
THR111.OG1-ASN107.O 46.67%
SER289.OG-ASP374.OD1 46.67%
TYR64.N-TYR71.O 43.81%
GLN548.N-ALA575.O 45.71%
PHE511.N-PRO529.O 46.67%
THR12.N-GLY3.O 43.81%
PHE511.N-PRO529.O 45.71%
TYR299.OH-TYR269.O 46.67%
PHE511.N-PRO529.O 42.86%
LEU65.N-PHE81.O 45.71%
PHE373.N-VAL397.O 45.71%
VAL154.N-ASP223.O 42.86%
HID164.N-GLU156.O 45.71%
VAL372.N-VAL305.O 45.71%
TYR198.N-PHE182.O 42.86%
ILE195.N-GLY184.O 45.71%
PHE546.N-LEU573.O 44.76%
TYR541.N-ARG567.O 42.86%
PHE373.N-VAL397.O 45.71%
CYS441.N-LYS462.O 44.76%
ASN381.ND2-ASN124.OD1 42.86%
PHE472.N-ILE572.O 43.81%
TYR198.N-PHE182.O 44.76%
PHE373.N-VAL397.O 42.86%
MET429.N-VAL425.O 43.81%
ILE333.N-PHE357.O 44.76%
LEU163.N-VAL209.O 41.90%
ILE333.N-PHE357.O 43.81%
TYR246.N-MET274.O 43.81%
ARG303.N-ASP369.OD2 41.90%
ILE304.N-GLN354.O 43.81%
ASN423.ND2-ALA379.O 43.81%
TYR48.OH-VAL42.O 41.90%
SER453.OG-VAL449.O 43.81%
THR111.OG1-ASN107.O 43.81%
THR183.N-VAL226.O 40.95%
PHE546.N-LEU573.O 42.86%
CYM5.N-SER10.O 43.81%
CYS441.N-LYS462.O 40.95%
GLY150.N-PRO172.O 42.86%
LEU25.N-LEU14.O 43.81%
ARG332.N-LYS347.O 40.95%
THR431.OG1-ARG427.O 42.86%
GLN281.NE2-ASP401.OD1 42.86%
THR137.OG1-PHE133.O 40.00%
VAL372.N-VAL305.O 42.86%
THR481.N-ILE488.O 41.90%
HID164.N-GLU156.O 40.00%
TYR198.OH-TYR217.O 42.86%
ARG443.NH1-THR566.O 41.90%
TYR120.OH-TRP114.O 40.00%
ASP315.N-HID311.O 42.86%
GLY66.N-SER69.O 41.90%
LEU43.N-ARG15.O 39.05%
ALA368.N-ARG392.O 42.86%
MET576.N-MET474.O 40.95%
PHE90.N-LEU83.O 39.05%
SER577.N-GLN548.OE1 41.90%
ASN489.ND2-THR549.O 40.95%
LEU65.N-PHE81.O 39.05%
PHE357.N-SER331.O 41.90%
SER555.OG-THR550.OG1 40.95%
ALA186.N-VAL193.O 39.05%
ARG443.NH1-THR566.O 41.90%
MET429.N-VAL425.O 40.95%
CYM5.N-SER10.O 39.05%
GLN243.NE2-TYR277.O 41.90%
SER453.OG-VAL449.O 40.95%
ASP315.N-HID311.O 39.05%
LEU280.N-TYR398.O 41.90%
THR153.N-SER166.O 40.95%
SER385.OG-ALA237.O 38.10%
ILE334.N-ASN349.OD1 41.90%
THR199.N-ARG212.O 40.00%
ILE195.N-GLY184.O 38.10%
TYR211.N-ALA161.O 40.95%
VAL193.N-ALA186.O 40.00%
ALA134.N-LEU130.O 38.10%
MET576.N-MET474.O 40.95%
ALA186.N-VAL193.O 40.00%
SER80.OG-PRO77.O 38.10%
THR137.OG1-PHE133.O 40.95%
ILE304.N-GLN354.O 40.00%
SER229.OG-GLU143.O 38.10%
TYR476.N-MET576.O 40.95%
GLN243.NE2-TYR277.O 40.00%
ALA368.N-ARG392.O 38.10%
ALA134.N-LEU130.O 40.95%
TYR543.OH-GLN470.OE1 40.00%
THR431.OG1-ARG427.O 38.10%
ASN562.ND2-ALA403.O 40.95%
VAL209.N-LEU163.O 40.00%
VAL209.N-LEU163.O 38.10%
GLN354.NE2-ALA302.O 40.00%
ILE512.N-ILE545.O 39.05%
ASP374.N-THR307.O 37.14%
TYR246.N-MET274.O 40.00%
TYR541.N-ARG567.O 39.05%
LEU325.N-ALA321.O 37.14%
CYS441.N-LYS462.O 39.05%
PHE225.N-ALA152.O 39.05%
MET576.N-MET474.O 37.14%
THR12.N-GLY3.O 39.05%
ARG332.N-LYS347.O 39.05%
THR501.OG1-ARG497.O 37.14%
TYR71.N-TYR64.O 39.05%
CYS30.N-CYM26.O 39.05%
THR153.N-SER166.O 37.14%
ARG332.N-LYS347.O 39.05%
THR286.OG1-PRO283.O 39.05%
TYR71.N-TYR64.O 37.14%
SER166.N-THR153.O 38.10%
LEU280.N-TYR398.O 39.05%
VAL226.N-THR183.O 36.19%
LEU138.N-ALA134.O 38.10%
GLY184.N-GLY196.O 39.05%
TYR211.N-ALA161.O 36.19%
TYR541.N-ARG567.O 38.10%
ASN489.ND2-LYS477.O 38.10%
ILE333.N-PHE357.O 36.19%
ASN489.ND2-THR549.O 37.14%
THR183.N-VAL226.O 38.10%
LEU590.N-ALA473.O 36.19%
THR380.OG1-ASP383.OD1 37.14%
ILE334.N-ASN349.OD1 38.10%
GLY66.N-SER69.O 36.19%
ILE545.N-VAL510.O 36.19%
ALA140.N-GLU136.O 38.10%
TYR70.OH-GLY91.O 36.19%
THR61.OG1-ASP59.OD2 36.19%
ALA368.N-ARG392.O 38.10%
THR547.OG1-ALA487.O 36.19%
LEU165.N-ASP207.O 36.19%
MET576.N-MET474.O 66.99 ILE545.N-VAL510.O 63.64
ALA134.N-LEU130.O 63.64 ILE545.N-VAL510.O 61.72
ARG186.NE-ASP223.OD1 85.17
ALA134.N-LEU130.O 72.25
ARG186.NE-ASP223.OD1 87.08
ALA134.N-LEU130.O 70.33
GLN548.N-ILE575.O 58.85
THR307.N-VAL372.O 55.98
VAL452.N-ILE448.O 54.55
MET429.N-VAL425.O 54.55 PHE357.N-SER331.O 54.07
LEU500.N-VAL496.O 55.02
ILE512.N-ILE545.O 54.55
ILE109.N-ASP105.O 53.59
ALA321.N-LEU317.O 53.59
TYR306.OH-ALA292.O 56.46
LYS473.NZ-TYR582.O 53.11 LEU500.N-VAL496.O 53.11
ALA321.N-LEU317.O 51.20 LEU325.N-ALA321.O 51.20
CYM5.N-SER10.O 53.59
ARG497.N-ILE493.O 53.11
LYS473.NZ-TYR582.O 53.11
LEU500.N-VAL496.O 53.11
PHE511.N-PRO529.O 49.76 ARG186.NH2-LYS218.O 49.76
GLN492.NE2-GLN548.O 52.15
TYR306.OH-ALA292.O 52.15
ASN489.N-GLN518.OE1 52.15
PHE546.N-LEU573.O 51.67
LEU455.N-THR451.O 50.72 LEU325.N-ALA321.O 50.72 ASN349.N-ARG332.O 50.72
VAL154.N-ASP223.O 48.33 LYS473.NZ-TYR582.O 48.33 ASN388.ND2-PRO238.O 47.85
GLU142.N-LEU138.O 50.72
SER523.N-ASN519.O 50.72
PHE357.N-SER331.O 50.24
ASP32.N-LYS28.O 51.20
ALA123.N-ASP119.O 50.24
GLN492.NE2-GLN548.O 49.28
LEU325.N-ALA321.O 50.24
GLN548.N-ILE575.O 50.24
PHE546.N-LEU573.O 50.72
LEU573.N-VAL544.O 48.80
ARG186.NH2-LYS218.O 51.20
LEU138.N-ALA134.O 50.72
ALA140.N-GLU136.O 51.20
SER166.N-THR153.O 52.15 TYR185.N-TYR224.O 51.20
LEU280.N-TYR398.O 51.20
ARG567.NE-SER539.O 49.28
GLN548.N-ILE575.O 52.15
ASN489.N-GLN518.OE1 51.67
VAL452.N-ILE448.O 51.67
LEU573.N-VAL544.O 52.15
ASP450.N-ALA446.O 52.63
THR12.OG1-LEU25.O 52.63
MET429.N-VAL425.O 53.59
MET429.N-VAL425.O 51.20
CYS358.N-TYR306.O 49.76
SER523.N-ASN519.O 50.72
PHE182.N-TYR198.O 52.63
MET429.N-VAL425.O 52.15
PHE472.N-ILE572.O 52.63
VAL154.N-ASP223.O 52.15
LEU280.N-TYR398.O 51.20
ASN489.N-GLN518.OE1 54.07
HID164.N-GLU156.O 54.55
TYR198.N-PHE182.O 52.63 LEU500.N-VAL496.O 52.15 MET576.N-MET474.O 51.67
TYR120.OH-TRP114.O 54.55
LEU325.N-ALA321.O 54.07
PHE225.N-ALA152.O 53.59
VAL154.N-ASP223.O 55.98
THR307.N-VAL372.O 55.98
CYM5.N-SER10.O 53.11
LYS569.N-TYR541.O 54.55
ASN388.ND2-PRO238.O 53.11
TYR306.OH-ALA292.O 53.59
LYS569.N-TYR541.O 54.55
ILE575.N-PHE546.O 54.55
VAL154.N-ASP223.O 55.98
CYS358.N-TYR306.O 55.50
VAL397.N-VAL371.O 55.50
PHE373.N-VAL397.O 57.42 LEU280.N-TYR398.O 56.46
ILE575.N-PHE546.O 54.07
VAL397.N-VAL371.O 55.02 TYR120.OH-TRP114.O 54.55
LYS473.NZ-TYR582.O 56.94
VAL372.N-VAL305.O 55.98
VAL372.N-VAL305.O 57.42
VAL397.N-VAL371.O 57.42
ARG497.N-ILE493.O 57.89
LEU25.N-LEU14.O 57.89
CYS426.N-ASN423.OD1 57.89
PHE225.N-ALA152.O 58.37
ILE575.N-PHE546.O 63.16
MET576.N-MET474.O 56.94
GLY400.N-LEU280.O 55.02
ASN489.N-GLN518.OE1 55.02
ILE512.N-ILE545.O 55.02
VAL372.N-VAL305.O 55.50
CYS426.N-ASN423.OD1 55.98
ARG507.NE-LEU500.O 55.98
PHE472.N-ILE572.O 58.85
SER523.N-ASN519.O 55.50
THR307.N-VAL372.O 57.42
TYR71.N-TYR64.O 56.94
ASP450.N-ALA446.O 57.42
TYR71.N-TYR64.O 56.94
HID164.N-GLU156.O 57.89
TYR64.N-TYR71.O 57.42
PHE373.N-VAL397.O 57.42
ILE545.N-VAL510.O 57.42
ILE545.N-VAL510.O 59.33
ALA321.N-LEU317.O 58.85
CYS426.N-ASN423.OD1 57.89
VAL372.N-VAL305.O 59.33
ARG129.NE-ASN9.OD1 59.33
ALA134.N-LEU130.O 62.20 ALA321.N-LEU317.O 59.33
LEU65.N-PHE81.O 56.94 TYR306.OH-ALA292.O 56.94
VAL397.N-VAL371.O 60.29
VAL452.N-ILE448.O 59.33
TYR64.N-TYR71.O 59.81
TYR120.OH-TRP114.O 59.33
SER385.OG-ALA237.O 58.37
ILE512.N-ILE545.O 62.68
PHE373.N-VAL397.O 57.42
PHE472.N-ILE572.O 60.77
ILE109.N-ASP105.O 60.77
LEU138.N-ALA134.O 61.24
PHE472.N-ILE572.O 63.64
THR307.N-VAL372.O 60.29
ARG497.N-ILE493.O 61.72
ILE575.N-PHE546.O 65.07
PHE373.N-VAL397.O 62.20
ILE512.N-ILE545.O 65.07
ARG186.NE-ASP223.OD1 88.52
CYS426.N-ASN423.OD1 64.11
ARG186.NE-ASP223.OD2 88.04
5-4_12212689 ARG186.NH2-ASP223.OD2 89.95
5-3_12212691
ARG186.NH2-ASP223.OD2 89.00
ARG186.NH2-ASP223.OD1 93.30
5-2_12212688
ARG186.NH2-ASP223.OD2 86.60
5-1_12212701
Open
Table 6.8 Stronger HBs (with occupancy rates .≥40%) during MDs’ rep1-rep5 of model-NSP13.1-open-ADPMg.2+ 5-5_12212693
ALA140.N-GLU136.O 50.24
VAL452.N-ILE448.O 50.72
LEU65.N-PHE81.O 50.72
TYR198.N-PHE182.O 50.72
TYR306.N-VAL356.O 51.20
GLY294.N-HID290.O 51.20
GLY184.N-GLY196.O 52.63
VAL154.N-ASP223.O 52.63
THR307.N-VAL372.O 53.11
GLN548.N-ILE575.O 53.11
VAL371.N-HID395.O 53.11
ALA321.N-LEU317.O 53.59
ILE575.N-PHE546.O 54.07
TYR306.OH-ALA292.O 54.07
ASN489.N-GLN518.OE1 54.55
CYM5.N-SER10.O 54.55
PHE225.N-ALA152.O 55.50
HID164.N-GLU156.O 55.50
LEU500.N-VAL496.O 55.98
CYS426.N-ASN423.OD1 56.46
PHE472.N-ILE572.O 56.46
LYS569.N-TYR541.O 56.46
LEU138.N-ALA134.O 56.46
VAL372.N-VAL305.O 57.42
LEU325.N-ALA321.O 57.42
LYS94.NZ-CYM29.SG 57.89
MET576.N-MET474.O 57.89
LYS473.NZ-TYR582.O 58.37
TYR120.OH-TRP114.O 58.37
ARG129.NE-ASN9.OD1 58.85
ILE109.N-ASP105.O 58.85
PHE373.N-VAL397.O 59.33
VAL397.N-VAL371.O 60.29
ILE545.N-VAL510.O 61.72
ILE512.N-ILE545.O 62.68
ALA134.N-LEU130.O 65.07
ARG186.NE-ASP223.OD1 85.17
ARG186.NH2-ASP223.OD2 89.95
256 6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA
ASN349.N-ARG332.O 46.89
TYR299.OH-TYR269.O 46.41
ASN388.ND2-PRO238.O 46.41
GLY66.N-SER69.O 46.41
LEU455.N-THR451.O 45.93
ASN220.N-ASP223.OD2 45.45
THR12.OG1-LEU25.O 45.45
ILE399.N-PHE373.O 49.28
THR125.OG1-ILE121.O 48.80
ARG186.NH2-LYS218.O 48.80
CYS318.N-VAL314.O 48.33
PHE357.N-SER331.O 48.33
ASN107.N-VAL103.O 47.37
LYS131.N-THR127.O 47.37
GLN492.NE2-GLN548.O 47.37
THR566.OG1-ASN562.O 46.89 ALA140.N-GLU136.O 46.89 ARG560.N-ASN557.OD1 46.89 TYR396.N-LYS276.O 46.41 ASP578.N-GLN548.OE1 46.41
VAL193.N-ARG186.O 45.45 THR141.OG1-THR137.O 45.45
GLU142.N-LEU138.O 44.50 ASP315.N-HID311.O 44.50 ASN220.N-ASP223.OD1 44.50 ASN349.N-ARG332.O 44.02 ASN107.N-VAL103.O 44.02 THR199.N-ARG212.O 44.02 ALA110.N-PHE106.O 43.54 SER166.N-THR153.O 43.54 VAL209.N-LEU163.O 43.54
ASN562.N-VAL558.O 45.45
ASN423.ND2-ALA379.O 44.50
LEU280.N-TYR398.O 44.50
GLY184.N-GLY196.O 44.02
TYR398.N-SER278.O 44.02
LEU83.N-LEU63.O 44.02
GLY294.N-HID290.O 44.02
VAL371.N-HID395.O 43.54
ILE525.N-VAL521.O 43.54
TYR211.OH-SER159.O 43.54
GLU143.N-LYS139.O 43.54
SER80.OG-PRO77.O 43.06
ASN107.N-VAL103.O 42.58
TYR382.OH-MET233.O 42.58
ARG332.NH2-ASP315.OD1 42.58
SER385.OG-ALA237.O 42.58
PHE561.N-ASN557.O 42.11
THR451.OG1-GLU447.O 42.11
CYS318.N-VAL314.O 42.11
THR125.OG1-ILE121.O 41.63
SER278.N-TYR396.O 41.63
LYS569.N-TYR541.O 41.63
PHE225.N-ALA152.O 47.37
CYS358.N-TYR306.O 46.89
LEU65.N-PHE81.O 45.93
TYR396.N-LYS276.O 45.93
ARG567.NE-SER539.O 45.45
TYR185.N-TYR224.O 45.45
ASN220.N-ASP223.OD2 45.45
SER166.N-THR153.O 44.98
HID164.N-GLU156.O 44.98
LYS569.N-TYR541.O 44.50
GLY294.N-HID290.O 44.50
ARG497.N-ILE493.O 44.50
TYR299.OH-TYR269.O 44.02
LEU573.N-VAL544.O 44.02
VAL6.N-PHE24.O 44.02
THR183.N-VAL226.O 44.02
GLU136.N-LEU132.O 44.02
LYS94.NZ-CYM29.SG 44.02
ARG332.NH2-ASP315.OD1 43.54
ILE333.N-PHE357.O 43.06
GLU143.N-LYS139.O 42.58
SER278.N-TYR396.O 42.58
GLN492.NE2-GLN548.O 43.54
ASN423.ND2-ALA379.O 43.54
GLY66.N-SER69.O 42.58
ILE35.N-TYR31.O 43.54
VAL305.N-ILE370.O 42.58
THR451.OG1-GLU447.O 43.54
THR231.N-ASN179.O 44.02
CYM5.N-SER10.O 43.06 GLY222.N-VAL154.O 42.58
TYR120.OH-TRP114.O 44.02
GLY294.N-HID290.O 44.02
PHE546.N-LEU573.O 43.06 VAL371.N-HID395.O 43.06
THR566.N-ASN562.O 44.50
VAL193.N-ARG186.O 43.06
GLY494.N-ARG490.O 44.50
PHE182.N-TYR198.O 43.06
THR183.N-VAL226.O 44.50
CYS358.N-TYR306.O 44.98
THR141.OG1-THR137.O 43.06 TYR185.N-TYR224.O 43.06
PHE561.N-ASN557.O 44.98
ALA292.N-LYS288.O 45.45
TYR71.N-TYR64.O 43.54 LEU428.N-SER424.O 43.06
GLU142.N-LEU138.O 45.45
TYR306.N-VAL356.O 43.54
SER385.OG-ALA237.O 45.45
THR144.OG1-ALA140.O 45.93
PHE357.N-SER331.O 47.37
LEU138.N-ALA134.O 44.50
ILE399.N-PHE373.O 48.33
THR183.N-VAL226.O 44.98 LEU438.N-GLN281.O 47.37
VAL371.N-HID395.O 48.33
ASN562.N-VAL558.O 45.45 GLY294.N-HID290.O 44.98
TYR306.N-VAL356.O 48.33
ILE333.N-PHE357.O 45.45
PHE511.N-PRO529.O 48.80
TYR198.N-PHE182.O 46.89
SER513.OG-ASN519.OD1 49.28 ASP450.N-ALA446.O 45.93
PHE546.N-LEU573.O 47.37
ARG507.NE-LEU500.O 49.28 SER513.OG-ASN519.OD1 48.80
PHE182.N-TYR198.O 49.28
SER513.OG-ASN519.OD1 46.41
SER166.N-THR153.O 47.37
PHE511.N-PRO529.O 49.28 PHE225.N-ALA152.O 45.93
LEU65.N-PHE81.O 49.28
TYR299.OH-TYR269.O 46.41
PHE511.N-PRO529.O 47.85
VAL456.N-VAL452.O 49.28 LEU138.N-ALA134.O 49.28
GLY184.N-GLY196.O 49.28
LEU25.N-LEU14.O 46.89
THR199.N-ARG212.O 47.85
ASN349.N-ARG332.O 49.76
LYS131.N-THR127.O 46.41
SER523.N-ASN519.O 49.28
HID164.N-GLU156.O 47.37
TYR198.N-PHE182.O 49.76
TYR185.N-TYR224.O 47.85
MET576.N-MET474.O 48.33
VAL305.N-ILE370.O 49.76 VAL181.N-SER229.O 49.28
VAL305.N-ILE370.O 49.76
TYR70.OH-LEU25.O 47.85
ILE333.N-PHE357.O 49.28
GLU142.N-LEU138.O 49.76 VAL456.N-VAL452.O 47.37
ILE109.N-ASP105.O 49.76
VAL452.N-ILE448.O 47.85
TYR198.N-PHE182.O 50.72
VAL305.N-ILE370.O 49.28
ASP315.N-HID311.O 49.76
GLN548.N-ILE575.O 47.85 ARG186.NH2-LYS218.O 50.24
PHE182.N-TYR198.O 49.76 ALA140.N-GLU136.O 47.85
ILE399.N-PHE373.O 49.76
ALA140.N-GLU136.O 49.76
VAL371.N-HID395.O 49.76
TYR299.OH-TYR269.O 41.63
PHE546.N-LEU573.O 42.11
(continued)
ASN423.ND2-ALA379.O 42.11
ASN107.N-VAL103.O 42.11
THR231.N-ASN179.O 42.11
LEU573.N-VAL544.O 42.58
VAL210.N-GLU201.O 43.06
SER513.OG-ASN519.OD1 43.06
GLY66.N-SER69.O 43.54
GLN492.NE2-GLN548.O 43.54
LYS131.N-THR127.O 44.02
PHE511.N-PRO529.O 44.02
TYR396.N-LYS276.O 44.02
VAL193.N-ARG186.O 44.02
SER278.N-TYR396.O 44.02
ILE35.N-TYR31.O 44.02
ASN388.ND2-PRO238.O 44.50
CYS358.N-TYR306.O 44.98
THR12.OG1-LEU25.O 44.98
ASN349.N-ARG332.O 45.45
TYR71.N-TYR64.O 45.45
PHE357.N-SER331.O 45.45
ARG567.NE-SER539.O 45.45
ARG497.N-ILE493.O 45.93
SER385.OG-ALA237.O 45.93
VAL305.N-ILE370.O 46.41
CYS318.N-VAL314.O 46.89
SER166.N-THR153.O 46.89
CYS574.N-PHE472.O 46.89
GLU142.N-LEU138.O 46.89
THR144.OG1-ALA140.O 47.37
ARG409.NE-GLU142.OE1 47.37
ARG186.NH2-LYS218.O 47.85
ARG409.NH2-GLU142.OE2 47.85
VAL181.N-SER229.O 48.80
SER523.N-ASN519.O 48.80
MET429.N-VAL425.O 48.80
TYR64.N-TYR71.O 49.28
TYR185.N-TYR224.O 49.28
PHE182.N-TYR198.O 49.76
6.4 Concluding Remarks 257
5-2_12212688
VAL226.N-THR183.O 41.63
GLY222.N-VAL154.O 41.63
LEU25.N-LEU14.O 41.15
LEU573.N-VAL544.O 41.15
VAL210.N-GLU201.O 41.15
THR431.N-ARG427.O 40.67
TYR246.N-MET274.O 40.67
LYS131.N-THR127.O 40.19
SER513.OG-ASN519.OD1 40.19
LEU428.N-SER424.O 40.19
GLY3.N-THR12.O 40.19
VAL193.N-ARG186.O 40.19
TYR306.N-VAL356.O 40.19
GLY400.N-LEU280.O 39.71
ARG507.NE-LEU500.O 39.71
TYR396.N-LYS276.O 39.71
ARG560.N-ASN557.OD1 39.71
THR12.N-GLY3.O 39.71
ALA123.N-ASP119.O 39.23
THR183.N-VAL226.O 39.23
5-1_12212701
ARG409.NH2-GLU142.OE2 42.58
THR451.OG1-GLU447.O 42.11
ASN423.ND2-ALA379.O 41.63
VAL226.N-THR183.O 41.63
TYR421.N-GLU418.O 41.63
TYR246.N-MET274.O 41.15
TYR306.N-VAL356.O 41.15
PHE291.N-GLY287.O 41.15
ILE525.N-VAL521.O 41.15
LEU25.N-LEU14.O 40.67
PHE561.N-ASN557.O 40.67
THR199.N-ARG212.O 40.67
GLY3.N-THR12.O 40.67
SER278.N-TYR396.O 40.19
ALA368.N-ARG392.O 40.19
THR144.OG1-ALA140.O 40.19
ARG560.N-ASN557.OD1 40.19
THR431.N-ARG427.O 39.71
THR12.OG1-LEU25.O 38.76
LEU391.N-VAL387.O 38.76
Open
Table 6.8 (continued)
ILE399.N-PHE373.O 39.23
LEU322.N-CYS318.O 39.71
SER331.N-TYR355.O 39.71
THR451.OG1-GLU447.O 39.71
GLU143.N-LYS139.O 40.19
TYR398.N-SER278.O 40.19
GLY3.N-THR12.O 40.19
ASP578.N-GLN548.OE1 40.19
THR153.N-SER166.O 40.67
ALA123.N-ASP119.O 40.67
LYS430.NZ-GLU420.OE1 40.67
THR255.N-TYR298.O 40.67
TYR421.N-GLU418.O 41.15
ASN423.ND2-ALA379.O 41.15
CYS574.N-PHE472.O 41.63
ARG409.NH2-GLU142.OE2 41.63
LEU455.N-THR451.O 41.63
CYS318.N-VAL314.O 41.63
GLN243.NE2-TYR277.O 41.63
GLY184.N-GLY196.O 42.58
5-3_12212691
LEU322.N-CYS318.O 39.23
VAL226.N-THR183.O 39.71
SER577.N-GLN548.OE1 39.71
GLU136.N-LEU132.O 39.71
GLN281.N-MET436.O 39.71
TYR398.N-SER278.O 40.19
VAL456.N-VAL452.O 40.19
GLU143.N-LYS139.O 40.67
THR431.OG1-ARG427.O 40.67
CYS318.N-VAL314.O 41.15
VAL210.N-GLU201.O 41.15
LYS131.N-THR127.O 41.15
ILE525.N-VAL521.O 41.63
SER331.N-TYR355.O 42.11
TYR299.OH-TYR269.O 42.11
ARG390.NH1-LEU363.O 42.58
ASN562.N-VAL558.O 42.58
ASN220.N-ASP223.OD2 42.58
THR431.N-ARG427.O 42.58
ASP315.N-HID311.O 43.06
5-4_12212689
GLY17.N-LEU41.O 37.80
GLY222.N-VAL154.O 38.28
TYR398.N-SER278.O 38.28
ASP450.N-ALA446.O 38.76
THR137.N-PHE133.O 38.76
LEU83.N-LEU63.O 38.76
PHE106.N-ASN102.O 39.23
ASN220.N-ASP223.OD2 39.71
THR141.OG1-THR137.O 39.71
ARG303.NE-GLU353.O 40.19
THR199.N-ARG212.O 40.19
ILE333.N-PHE357.O 40.19
GLU143.N-LYS139.O 40.19
ALA123.N-ASP119.O 40.19
LEU455.N-THR451.O 40.67
ASP315.N-HID311.O 40.67
ASN562.N-VAL558.O 40.67
ILE399.N-PHE373.O 41.15
TYR246.N-MET274.O 41.15
LEU280.N-TYR398.O 41.63
5-5_12212693
258 6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA
PHE373.N-VAL397.O 61.24 CYM5.N-SER10.O 58.37
THR307.N-VAL372.O 57.89 CYS30.N-CYM26.O 57.89
THR307.N-VAL372.O 58.85
ILE575.N-PHE546.O 58.85
ARG129.NE-ASN9.OD1 59.33
ASP450.N-ALA446.O 56.94 VAL372.N-VAL305.O 56.94
LEU138.N-ALA134.O 57.42
PHE225.N-ALA152.O 56.94
ALA140.N-GLU136.O 57.42
THR307.N-VAL372.O 57.42
ASN107.N-VAL103.O 56.46
ILE545.N-VAL510.O 54.55 LYS473.NZ-TYR582.O 54.55 VAL372.N-VAL305.O 54.07
CYM5.N-SER10.O 53.59 ILE109.N-ASP105.O 53.59 ARG507.NE-LEU500.O 52.63 ILE545.N-VAL510.O 52.63
ASP315.N-HID311.O 55.50
ARG332.NH2-ASP315.OD2 55.02
THR37.OG1-HID33.O 55.02
ILE35.N-TYR31.O 54.55
CYM5.N-SER10.O 55.98
ASN349.N-ARG332.O 55.02
LEU500.N-VAL496.O 54.55
ALA321.N-LEU317.O 53.59
PHE182.N-TYR198.O 53.59 LEU325.N-ALA321.O 53.59
TYR198.N-PHE182.O 52.63 ALA321.N-LEU317.O 52.63
ARG186.NH2-LYS218.O 51.20 ALA321.N-LEU317.O 51.20
ARG507.NE-LEU500.O 53.59
ASN107.N-VAL103.O 53.59
HID164.N-GLU156.O 53.59
PHE472.N-ILE572.O 53.11
TYR299.OH-TYR269.O 51.67
LYS473.NZ-TYR582.O 51.67
VAL154.N-ASP223.O 51.20
ARG332.NH2-ASP315.OD2 51.20
LEU325.N-ALA321.O 50.24
VAL305.N-ILE370.O 51.67
ILE399.N-PHE373.O 52.63
ILE575.N-PHE546.O 52.63
ASP450.N-ALA446.O 53.11
CYS426.N-ASN423.OD1 52.63 ASN562.N-VAL558.O 52.15 HID164.N-GLU156.O 51.67
LYS131.N-THR127.O 54.55
GLN548.N-ILE575.O 54.07
ARG497.N-ILE493.O 53.59
VAL305.N-ILE370.O 54.07
PHE472.N-ILE572.O 55.98
SER166.N-THR153.O 52.15
LEU138.N-ALA134.O 54.55
CYS426.N-ASN423.OD1 52.15
LYS569.N-TYR541.O 53.11
LEU138.N-ALA134.O 55.02
LEU43.N-ARG15.O 53.59
VAL371.N-HID395.O 56.46
VAL452.N-ILE448.O 55.98
MET429.N-VAL425.O 55.98
CYS426.N-ASN423.OD1 56.46 PHE225.N-ALA152.O 55.98
LEU325.N-ALA321.O 55.98
PHE357.N-SER331.O 56.46
SER166.N-THR153.O 56.46
LYS473.NZ-TYR582.O 56.46
ARG497.N-ILE493.O 56.46
LEU500.N-VAL496.O 56.94
SER385.OG-ALA237.O 57.42
ILE334.N-ASN349.OD1 57.89
ILE493.N-ASN489.O 58.37
ARG567.NE-SER539.O 58.37
PHE357.N-SER331.O 58.37
VAL397.N-VAL371.O 61.24
LEU280.N-TYR398.O 56.46
ILE399.N-PHE373.O 56.94 PHE225.N-ALA152.O 56.46
VAL397.N-VAL371.O 56.94
ILE545.N-VAL510.O 56.46
ILE109.N-ASP105.O 56.46
VAL397.N-VAL371.O 56.94
PHE225.N-ALA152.O 56.94
ILE109.N-ASP105.O 56.94
ARG129.NE-ASN9.OD1 57.42
VAL154.N-ASP223.O 57.42
ILE512.N-ILE545.O 57.89
MET429.N-VAL425.O 57.89
TYR120.OH-TRP114.O 57.89
ASN489.N-GLN518.OE1 57.42
CYS574.N-PHE472.O 58.85
CYS358.N-TYR306.O 62.68 LEU65.N-PHE81.O 62.20
PHE546.N-LEU573.O 58.85
ARG497.N-ILE493.O 60.77 LEU65.N-PHE81.O 59.81
CYS426.N-ASN423.OD1 59.33
VAL372.N-VAL305.O 59.33
TYR306.OH-ALA292.O 60.29
VAL372.N-VAL305.O 59.33
TYR306.OH-ALA292.O 62.68
ARG497.N-ILE493.O 63.64
ILE512.N-ILE545.O 61.72
PHE373.N-VAL397.O 61.72
TYR306.OH-ALA292.O 62.20
CYM5.N-SER10.O 62.20
SER385.OG-ALA237.O 61.24
THR125.OG1-ILE121.O 60.77
ALA134.N-LEU130.O 71.77 ILE512.N-ILE545.O 67.46 ILE109.N-ASP105.O 66.03
TYR306.OH-ALA292.O 65.55 VAL397.N-VAL371.O 64.11 SER385.OG-ALA237.O 61.72
SER385.OG-ALA237.O 65.07
ALA134.N-LEU130.O 63.16
PHE373.N-VAL397.O 63.16
PHE373.N-VAL397.O 62.68
LEU138.N-ALA134.O 61.24
PHE511.N-PRO529.O 64.11
ARG186.NE-ASP223.OD1 86.12
ALA134.N-LEU130.O 68.42
ARG186.NH2-ASP223.OD2 88.52 ARG332.NE-ASP315.OD1 73.68
ALA134.N-LEU130.O 68.90
ARG186.NE-ASP223.OD1 83.73
LYS94.NZ-CYM29.SG 68.90
ARG186.NH2-ASP223.OD2 91.39 ARG186.NE-ASP223.OD1 80.86
6-4_12225240 ARG186.NE-ASP223.OD1 90.43
6-3_12225255 ARG186.NH2-ASP223.OD2 92.34
6-2_12225258
ARG186.NH2-ASP223.OD2 89.47
6-1_12225252
Close
Table 6.9 Stronger HBs (with occupancy rates .≥40%) during MDs’ rep1-rep5 of model-NSP13.1-close-ADPMg.2+ 6-5_12225249
THR481.N-ILE488.O 51.20
LEU43.N-ARG15.O 51.20
ASN349.N-ARG332.O 51.67
ARG129.NE-ASN9.OD1 51.67
CYS574.N-PHE472.O 52.15
LEU325.N-ALA321.O 52.15
SER385.OG-ALA237.O 52.15
TYR120.OH-TRP114.O 52.15
(continued)
SER513.OG-ASN519.OD1 52.63
PHE225.N-ALA152.O 53.11
PHE546.N-LEU573.O 53.59
MET429.N-VAL425.O 53.59
HID164.N-GLU156.O 53.59
ASP315.N-HID311.O 54.07
PHE511.N-PRO529.O 54.07
ALA321.N-LEU317.O 55.50
GLN548.N-ILE575.O 55.50
VAL154.N-ASP223.O 56.46
CYM5.N-SER10.O 56.94
THR12.OG1-LEU25.O 57.89
LYS569.N-TYR541.O 57.89
ILE575.N-PHE546.O 58.37
CYS426.N-ASN423.OD1 58.85
VAL397.N-VAL371.O 59.33
VAL372.N-VAL305.O 60.29
THR307.N-VAL372.O 60.77
LEU280.N-TYR398.O 63.64
PHE373.N-VAL397.O 64.11
MET576.N-MET474.O 66.03
ASN489.N-GLN518.OE1 67.94
ILE512.N-ILE545.O 69.38
ALA134.N-LEU130.O 73.68
ARG186.NE-ASP223.OD1 87.56
ARG186.NH2-ASP223.OD2 88.52
6.4 Concluding Remarks 259
6-2_12225258
PHE511.N-PRO529.O 52.63
CYS318.N-VAL314.O 52.63
ALA321.N-LEU317.O 52.63
ARG129.NE-ASN9.OD1 52.63
LEU500.N-VAL496.O 52.15
ALA123.N-ASP119.O 52.15
SER523.N-ASN519.O 52.15
TYR120.OH-TRP114.O 52.15
THR431.OG1-ARG427.O 51.67
ASN349.N-ARG332.O 51.67
ILE399.N-PHE373.O 51.20
LEU325.N-ALA321.O 50.72
VAL154.N-ASP223.O 49.76
TYR198.N-PHE182.O 49.76
LEU573.N-VAL544.O 49.76
CYS358.N-TYR306.O 49.76
PHE291.N-GLY287.O 49.28
THR125.OG1-ILE121.O 48.80
VAL305.N-ILE370.O 48.80
PHE357.N-SER331.O 48.80
GLY222.N-VAL154.O 48.33
LYS569.N-TYR541.O 48.33
TYR306.N-VAL356.O 48.33
SER453.N-VAL449.O 47.85
TYR269.N-ASN265.O 47.85
TYR299.OH-TYR269.O 47.37
LEU322.N-CYS318.O 46.41
TYR398.N-SER278.O 46.41
VAL210.N-GLU201.O 46.41
LYS94.NZ-ASP32.OD1 45.93
LEU25.N-LEU14.O 44.98
TYR396.N-LYS276.O 44.98
ARG186.NH2-LYS218.O 44.98
LYS288.NZ-ASP374.OD1 44.98
TYR71.N-TYR64.O 44.50
PHE182.N-TYR198.O 44.02
6-1_12225252
ILE512.N-ILE545.O 51.20
ILE575.N-PHE546.O 50.72
HID164.N-GLU156.O 50.24
ASP315.N-HID311.O 50.24
LYS131.N-THR127.O 50.24
ALA123.N-ASP119.O 50.24
VAL452.N-ILE448.O 49.76
CYS358.N-TYR306.O 49.28
PHE472.N-ILE572.O 49.28
TYR306.N-VAL356.O 49.28
ASN388.ND2-PRO238.O 49.28
ILE399.N-PHE373.O 48.33
TYR185.N-TYR224.O 47.85
CYS318.N-VAL314.O 47.37
PHE357.N-SER331.O 46.89
ILE525.N-VAL521.O 46.89
GLN492.NE2-GLN548.O 46.41
ASN107.N-VAL103.O 45.93
PHE561.N-ASN557.O 45.45
CYS574.N-PHE472.O 44.98
SER453.N-VAL449.O 44.50
TYR398.N-SER278.O 44.50
TYR246.N-MET274.O 44.50
SER36.OG-ASP32.O 44.50
LEU573.N-VAL544.O 44.50
VAL305.N-ILE370.O 44.50
THR183.N-VAL226.O 44.02
ARG186.NH2-LYS218.O 44.02
SER523.N-ASN519.O 43.54
GLY294.N-HID290.O 43.06
ILE334.N-ASN349.OD1 43.06
GLN492.NE2-TYR476.O 43.06
ASP450.N-ALA446.O 42.58
TYR198.N-PHE182.O 42.58
THR431.N-ARG427.O 42.11
SER278.N-TYR396.O 42.11
Close
Table 6.9 (continued)
ILE333.N-PHE357.O 44.50
SER453.N-VAL449.O 44.50
ILE35.N-TYR31.O 44.98
TYR299.OH-TYR269.O 44.98
LEU83.N-LEU63.O 44.98
PHE472.N-ILE572.O 45.45
TYR398.N-SER278.O 45.93
GLY294.N-HID290.O 45.93
THR12.OG1-LEU25.O 45.93
LEU25.N-LEU14.O 45.93
TYR185.N-TYR224.O 45.93
PHE511.N-PRO529.O 46.41
VAL34.N-CYS30.O 46.41
THR125.OG1-ILE121.O 46.41
VAL371.N-HID395.O 46.41
ALA140.N-GLU136.O 46.89
TYR198.N-PHE182.O 46.89
MET576.N-MET474.O 46.89
ILE334.N-ASN349.OD1 46.89
THR183.N-VAL226.O 46.89
SER166.N-THR153.O 46.89
CYS318.N-VAL314.O 47.37
SER36.OG-ASP32.O 47.37
VAL89.N-CYS27.O 47.37
ASN349.N-ARG332.O 47.37
ILE575.N-PHE546.O 47.85
ALA123.N-ASP119.O 47.85
THR286.OG1-LEU438.O 47.85
ASN388.ND2-PRO238.O 48.33
LEU573.N-VAL544.O 48.33
VAL456.N-VAL452.O 48.80
MET429.N-VAL425.O 48.80
ILE565.N-PHE561.O 49.28
PHE546.N-LEU573.O 49.28
TYR120.OH-TRP114.O 49.76
ASN220.N-ASP223.OD2 49.76
6-3_12225255
LEU25.N-LEU14.O 43.06
THR37.OG1-HID33.O 43.06
LYS569.N-TYR541.O 43.06
TYR185.N-TYR224.O 43.54
LEU573.N-VAL544.O 44.50
VAL6.N-PHE24.O 44.50
TYR299.OH-TYR269.O 44.50
THR183.N-VAL226.O 44.50
ALA123.N-ASP119.O 44.98
ARG337.NH2-GLU197.OE2 44.98
ASN423.ND2-ALA379.O 44.98
GLY66.N-SER69.O 45.45
SER523.N-ASN519.O 45.45
PHE511.N-PRO529.O 45.93
ALA520.N-ASN516.O 45.93
CYS30.N-CYM26.O 46.41
MET429.N-VAL425.O 47.37
VAL371.N-HID395.O 47.85
THR125.OG1-ILE121.O 47.85
GLY294.N-HID290.O 48.33
TYR64.N-TYR71.O 48.80
ARG178.NE-GLU201.OE1 49.28
ARG337.NE-GLU197.OE1 49.28
HID164.N-GLU156.O 49.28
THR199.N-ARG212.O 49.76
LYS131.N-THR127.O 49.76
ASN388.ND2-PRO238.O 49.76
VAL210.N-GLU201.O 50.24
ARG129.NE-ASN9.OD1 50.72
THR307.N-VAL372.O 51.20
SER166.N-THR153.O 51.20
TYR476.N-MET576.O 51.67
CYS574.N-PHE472.O 52.15
THR12.OG1-LEU25.O 52.15
VAL154.N-ASP223.O 52.15
TYR120.OH-TRP114.O 52.15
6-4_12225240
GLY184.N-GLY196.O 43.54
GLY66.N-SER69.O 44.02
LEU25.N-LEU14.O 44.02
TYR71.N-TYR64.O 44.02
VAL193.N-ARG186.O 44.98
ASN489.ND2-THR549.O 44.98
SER166.N-THR153.O 44.98
LEU65.N-PHE81.O 44.98
VAL210.N-GLU201.O 45.93
ARG497.N-ILE493.O 45.93
THR125.OG1-ILE121.O 45.93
ILE545.N-VAL510.O 45.93
ASN388.ND2-PRO238.O 45.93
THR451.OG1-GLU447.O 45.93
TYR541.N-ARG567.O 46.41
CYS358.N-TYR306.O 46.41
LEU138.N-ALA134.O 46.41
TYR185.N-TYR224.O 46.89
ALA123.N-ASP119.O 46.89
ILE333.N-PHE357.O 46.89
LYS131.N-THR127.O 47.37
ILE399.N-PHE373.O 47.37
LEU500.N-VAL496.O 47.37
THR532.N-SER535.OG 47.85
TYR299.OH-TYR269.O 47.85
ASN220.N-ASP223.OD2 48.33
ALA522.N-GLN518.O 48.80
ALA140.N-GLU136.O 49.28
ARG186.NH2-LYS218.O 49.76
TYR198.N-PHE182.O 49.76
SER523.N-ASN519.O 50.24
VAL371.N-HID395.O 50.24
CYS318.N-VAL314.O 50.24
PHE357.N-SER331.O 50.72
ILE109.N-ASP105.O 51.20
TYR306.OH-ALA292.O 51.20
6-5_12225249
260 6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA
ALA140.N-GLU136.O 42.11 ARG507.NE-LEU500.O 42.11 ASN107.N-VAL103.O 41.63 ARG390.NH1-LEU363.O 41.63 TYR398.N-SER278.O 41.63 VAL387.N-ASP383.O 41.63 MET576.N-MET474.O 41.15 GLY222.N-VAL154.O 41.15
THR37.OG1-HID33.O 44.50 TYR476.N-MET576.O 44.02 TYR64.N-TYR71.O 44.02 GLY150.N-PRO172.O 43.54 TYR306.N-VAL356.O 43.54 THR255.N-TYR298.O 43.54 THR451.OG1-GLU447.O 43.06 LYS131.N-THR127.O 43.06
ASN381.ND2-ASN124.OD1 43.54
THR141.OG1-THR137.O 43.54
ARG390.NH1-LEU363.O 43.54
ASN423.ND2-ALA379.O 43.06
ILE333.N-PHE357.O 43.06
TYR185.N-TYR224.O 41.15
ASN562.N-VAL558.O 40.67
TYR421.N-GLU418.O 40.67
PHE561.N-ASN557.O 40.67
MET576.N-MET474.O 40.19
VAL209.N-LEU163.O 40.19
ALA140.N-GLU136.O 40.19
ARG337.NE-GLU197.OE1 40.19
PHE546.N-LEU573.O 39.71
VAL456.N-VAL452.O 39.71
GLY184.N-GLY196.O 39.71
GLU142.N-LEU138.O 39.23
ASN388.ND2-PRO238.O 39.23
TYR246.N-MET274.O 39.23
GLN270.N-VAL266.O 39.23
ARG560.NE-VAL533.O 39.23
LYS146.NZ-GLU143.OE1 38.76
THR12.OG1-LEU25.O 38.76
THR183.N-VAL226.O 38.76
LEU280.N-TYR398.O 38.76
ILE334.N-ASN349.OD1 38.28
THR199.N-ARG212.O 41.63
VAL371.N-HID395.O 41.63
ALA578.N-GLN548.OE1 41.15
PHE182.N-TYR198.O 41.15
THR141.OG1-THR137.O 41.15
GLN270.N-VAL266.O 41.15
LEU25.N-LEU14.O 40.67
MET576.N-MET474.O 40.67
THR12.OG1-LEU25.O 40.67
VAL193.N-ARG186.O 40.67
ASN423.ND2-ALA379.O 40.19
CYS30.N-CYM26.O 40.19
ARG337.NE-GLU197.OE1 40.19
VAL6.N-PHE24.O 40.19
LEU590.N-LYS473.O 40.19
PHE106.N-ASN102.O 39.71
ALA522.N-GLN518.O 39.23
LEU438.N-GLN281.O 39.23
ILE35.N-TYR31.O 39.23
ASN220.N-ASP223.OD2 39.23
ASN381.ND2-ASN124.OD1 39.23
VAL209.N-LEU163.O 38.76
ARG129.NH1-SER236.O 38.76
TYR355.N-LYS329.O 38.76
THR255.N-TYR298.O 38.76
THR451.OG1-GLU447.O 38.76
GLN492.N-ASN489.OD1 39.71
SER523.N-ASN519.O 40.19
SER278.N-TYR396.O 39.23
VAL193.N-ARG186.O 39.23
HID395.ND1-GLN275.O 39.23 ARG129.NH1-SER236.O 39.23
TYR246.N-MET274.O 39.23
LEU322.N-CYS318.O 39.71
SER331.OG-LYS347.O 39.23
LYS146.NZ-THR228.O 39.71
ARG332.NH2-ASP315.OD1 40.67 TYR396.N-LYS276.O 40.19
THR255.N-TYR298.O 39.71
GLY400.N-LEU280.O 39.71
TYR71.N-TYR64.O 40.67
LEU280.N-TYR398.O 40.19
THR359.OG1-ASN361.OD1 40.19
ASP315.N-HID311.O 41.63 CYS358.N-TYR306.O 40.67
GLN548.N-ILE575.O 40.19
LYS569.N-TYR541.O 41.63 VAL210.N-GLU201.O 40.67
GLN270.N-VAL266.O 40.19
ILE333.N-PHE357.O 40.67
THR199.N-ARG212.O 42.11 GLN492.N-ASN489.OD1 41.63
ASN220.N-ASP223.OD2 40.67
ALA368.N-ARG392.O 42.11
ARG186.NH2-LYS218.O 41.15
TYR246.N-MET274.O 42.58 ARG178.NH2-GLU201.OE2 41.15
ILE35.N-TYR31.O 41.15
VAL452.N-ILE448.O 42.58 PHE182.N-TYR198.O 42.11
VAL34.N-CYS30.O 41.15
LEU500.N-VAL496.O 42.58
GLY150.N-PRO172.O 42.11
ILE493.N-ASN489.O 44.50
ASP450.N-ALA446.O 43.54
TYR71.N-TYR64.O 42.58
GLY3.N-THR12.O 44.50
ASN220.N-ASP223.OD2 44.02
ARG409.NH2-GLU142.OE2 42.11
GLN492.N-ASN489.OD1 42.11
THR183.N-VAL226.O 40.19
ARG409.NH2-GLU142.OE2 40.67
ARG409.NE-GLU142.OE1 40.67
ARG390.NH1-LEU363.O 40.67
TYR398.N-SER278.O 40.67
THR199.N-ARG212.O 40.67
VAL209.N-LEU163.O 41.15
GLY3.N-THR12.O 41.15
GLN270.N-VAL266.O 41.15
TYR306.N-VAL356.O 41.63
ALA368.N-ARG392.O 41.63
VAL6.N-PHE24.O 41.63
THR153.N-SER166.O 41.63
GLN281.N-MET436.O 41.63
GLY494.N-ARG490.O 41.63
THR255.N-TYR298.O 42.11
GLY222.N-VAL154.O 42.11
PHE182.N-TYR198.O 42.11
ASP450.N-ALA446.O 42.11
ILE525.N-VAL521.O 42.11
TYR476.N-MET576.O 42.11
VAL387.N-ASP383.O 42.58
VAL305.N-ILE370.O 42.58
ASN562.N-VAL558.O 42.58
THR431.N-ARG427.O 42.58
ALA578.N-GLN548.OE1 43.06
THR286.OG1-LEU438.O 43.06
CYS30.N-CYM26.O 43.54
6.4 Concluding Remarks 261
262 Table 6.10 All the MDs show that the segment ASN51-GLY91 of NSP13 has large RMSFs
6 RNA Helicase Binding with .ADP-Mg2+ , .ATP-Mg2+ , and RNA NSP13-ATPMg.2+ -RNA
NSP13-ADPMg.2+ -RNA
NSP13-ATPMg.2+
NSP13-ADPMg.2+
NSP13.1-open-ADPMg.2+
NSP13.1-close-ADPMg.2+
1-1_12970406
51-91
1-2_12970408
51-91
1-3_12970412
51–91, 191
2-1_12258863
51–91, 151–221, 341, 481
2-2_12258865
51–91, 151–221, 341, 481
2-3_12251869
41–91
3-1_12258868
51–91
3-2_12257092
51–91, 151–221, 501
3-3_12259873
51–91
4-1_12257049
51–91
4-2_12251866
51–91, 151–221, 341, 481
4-3_12251868
51–91
5-1_12212701
51–91, 151–221, 471–531, 541–581
5-2_12212688
51–91, 151–221, 471–531, 551–581
5-3_12212691
51–91, 151–221, 471–531
5-4_12212689
51–91, 151–221, 471–581
5-5_12212693
51–91, 151–221, 471–531, 541–581
6-1_12225252
51–91, 151–231, 481, 551
6-2_12225258
51–91, 191–221, 441–581
6-3_12225255
51–91, 151–221, 461–581
6-4_12225240
51–91, 151–221, 481–581
6-5_12225249
51–91, 191, 461
Table 6.11 The residues of NSP13 binding with RNA-6CCCAUGUG13 of each optimized model NSP13-ATPMg.2+ -RNA_1-1_12970406
139, 142, 146, 175, 177, 179, 180, 230, 231, 232, 233, 234, 311, 333, 334, 335, 336, 337, 360, 361, 362, 363, 382, 383, 386, 390, 408, 409, 410, 412, 413, 414, 415, 416, 481, 482, 485, 486, 487, 514, 515, 516, 532, 534, 535, 550, 554
NSP13-ATPMg.2+ -RNA_1-2_12970408
139, 142, 143, 177, 178, 179, 180, 181, 197, 202, 228, 230, 231, 311, 336, 337, 360, 361, 382, 383, 386, 390, 408, 409, 410, 412, 413, 415, 416, 417, 485, 486, 514, 515, 516, 517, 532, 534, 535, 554, 560
NSP13-ATPMg.2+ -RNA_1-3_12970412
139, 142, 143, 177, 178, 179, 180, 181, 197, 202, 228, 230, 231, 311, 336, 337, 360, 361, 382, 383, 386, 390, 408, 409, 410, 412, 413, 415, 416, 417, 485, 486, 514, 515, 516, 517, 532, 534, 535, 554, 560
NSP13-ADPMg.2+ -RNA_2-1_12258863
139, 142, 143, 145, 146, 149, 175, 177, 178, 179, 180, 230, 231, 233, 310, 311, 335, 337, 340, 361, 362, 363, 364, 365, 378, 380, 382, 383, 390, 406, 407, 408, 409, 410, 480, 482, 485, 486, 487, 514, 515, 516, 517, 532, 534, 535, 550, 552, 554, 555, 560
NSP13-ADPMg.2+ -RNA_2-2_12258865
139, 142, 143, 145, 146, 149, 175, 177, 178, 179, 180, 230, 231, 233, 310, 311, 335, 337, 340, 361, 362, 363, 364, 365, 378, 380, 382, 383, 390, 406, 407, 408, 409, 410, 480, 482, 485, 486, 487, 514, 515, 516, 517, 532, 534, 535, 550, 552, 555, 554, 560
NSP13-ADPMg.2+ -RNA_2-3_12251869
139, 142, 143, 145, 146, 149, 175, 177, 178, 179, 180, 230, 231, 233, 310, 311, 335, 337, 340, 361, 362, 363, 364, 365, 378, 380, 382, 383, 390, 406,407, 408, 409, 410, 480, 482, 485, 486, 487, 514, 515, 516, 517, 532, 534, 535, 550, 552, 554, 555, 560
Chapter 7
Spike (S) Glycoprotein
Abstract Coronavirus SARS-CoV-2 spike glycoproteins (S-proteins) promote entry into cells and are the main target of antibodies and inhibitors. Angiotensinconverting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2 and is an antiviral drug target against SARS-CoV-2. This chapter is doing molecular dynamics (MD) studies of their structures and presenting some structural bioinformatics for developing therapies of the currently fatal COVID-19 virus. From SARS-CoV-2 S, we found (i) a strong polar contact between ASP442 and ARG509 in the receptor-binding domain (RBD) of each monomer, (ii) strong hydrogen bond (HB) PHE43.N-PHE565.O and their side-chain .π -.π stackings between each two monomers, and (iii) strong polar contacts between GLU1031 and ARG1039/LYS1038 in the central helix-connector domain (CHCD) between each two monomers; thus holding the three monomers tightly from both ends to the middle of the spike; in the spike HB C:TYR369.OHA:THR415.OG1 also has high occupancy rate, i.e., 50.30%. From the bindings of SARS-CoV-2 S (denoted as F-chain) and human ACE2 (denoted as D-/B-chain), we found that polar contacts F:LYS417-D:ASP30, F:ARG439-B:GLU329, and HB F:THR500.OG1-D:ASP355.OD1 are very strong during MD of 10 .μs, and salt bridges (SBs) F:LYS458-D/B:GLU23 (but D/B:GLU23 is with high HB occupancy rates with D/B:THR27), F:ARG403-D/B:GLU37 (also with low HB occupancy rates), F:GLU484-D/B:LYS31, and F:ARG403-D/B:ASP38 (but HB D/B:ASP38F:TYR449 is strong) are weak during the whole 10 .μs; during the whole 10 .μs, spike SBs F:ASP398-F:ARG355 and F:ASP442-F:ARG509 and the human ACE2 SBs GLU182-ARG115, GLU208-ARG219, GLU406-ARG518, GLU435-LYS541, GLU310-ARG306, GLU433-LYS288, and GLU189-LYS112 are always strong in MD of 10 .μs. Keywords Coronavirus SARS-CoV-2 spike · Human angiotensin-converting enzyme 2 · Receptor bindings · Optimization-based molecular dynamics studies · New structural bioinformatics
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_7
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7.1 Introduction “Coronavirus” (CoV) is an umbrella term for a family of viruses that share similar properties. Some coronaviruses have been behind concerning disease outbreaks, namely, SARS, MERS, and SARS-CoV-2. The SARS-CoV-2 (severe acute respiratory syndrome (SARS) coronavirus 2) is the disease at the center of our current global health crisis of COVID-19. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. The cryo-EM structures of the SARS-CoV-2 S ectodomain trimer were determined with PDB entries 6VXX (closed SARS-CoV-2 S) and 6VYB (SARS-CoV-2 S with one SB open) [363, 372]. The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE2, is a type I integral membrane protein of 805 amino acids that contains one HEXXH + E zinc-binding consensus sequence, and it has been implicated in the regulation of heart function and also as a functional receptor for coronavirus such as SARS and SARS-CoV-2 [359]. To gain further insights into this enzyme, the first crystal structures of the native (PDB entry 1R42) and inhibitor-bound (PDB entry 1R4L) forms of the ACE2 extracellular domains were solved to 2.2- and 3.0-Å resolution, respectively [359]. ACE2 is the cellular receptor for SARS-CoV-2; the cryo-EM structure for the SARS-CoV-2 S receptor-binding domain (RBD) in complex with ACE2 (in the presence of a neutral amino acid transporter B.0 AT1) was determined with PDB entry 6M71 [387]. Another SARS-CoV-2 S-RBD in complex with human ACE2 structure is the crystal structure with PDB entry 6VW1. SARS-CoV-2 and SARS recognize the same ACE2 in humans. The structure was determined by molecular replacement using the structure of SARS RBD complexed with ACE2 as the search template (PDB entry 2AJF) [317]. This chapter will perform MD computations of these six structures (with PDB entries 6VXX, 6VYB, 1R4L, 1R42, 6M17, and 6VW1) to reveal some structural bioinformatics for developing therapies of the currently fatal COVID-19.
7.2 Materials and Methods 7.2.1 Trimeric SARS-CoV-2 S For the SARS-CoV-2 trimeric spike, its MD materials and methods can be seen from [321]: “Two 10 .μs simulation trajectories of the trimeric SARS-CoV-2 spike glycoprotein with additional loop structures and glycan chains. Trajectory 1 was initiated in the closed state (PDB entry 6VXX), and trajectory 2 in a partially opened state (PDB entry 6VYB). The simulations used the Amber ff99SB-ILDN force field for proteins, the TIP3P model for water, and the Amber Glycam force field for the glycosylated parts of the system. The C- and N-peptide termini are capped with
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amide and acetyl groups respectively. The system was neutralized and salted with NaCl, with a final concentration of 0.15 M. The interval between frames is 1.2 ns. The simulations were conducted at 310 K in the NPT ensemble.” We denote the trimeric spike models as the 6VXX-trimeric-spike-closed-model-1 and the 6VYBtrimeric-spike-opened-model-2, respectively.
7.2.2 Human ACE2 For the human ACE2 ectodomain, in [321] two trajectories were initiated in an inhibitor-bound closed state (PDB entry 1R4L) and in an apo open state (PDB entry 1R42), respectively. Their simulations “used the Amber ff99SB-ILDN force field for proteins, the TIP3P model for water, and the generalized Amber force field for glycosylated asparagine. The C- and A-peptide termini, including those exposed due to missing loops in the published structural models, are capped with amide and acetyl groups respectively. The system was neutralized and salted with NaCl, with a final concentration of 0.15 M. The interval between frames is 1.2 ns. The simulations were conducted at 310 K in the NPT ensemble.” We denote the ACE2 models as the 1R4L-ACE2-closed-model-3 and the 1R42-ACE2-opened-model-4, respectively.
7.2.3 Binding of SARS-CoV-2 S-RBD and Human ACE2 For the SARS-CoV-2 spike receptor-binding domain (RBD) in complex with ACE2, in [321], we find two trajectories for PDB entries 6M17 and 6VW1, respectively. For 6M17.pdb, D-chain 21–612 (i.e., the peptidase domain (PD) [359] of ACE2) and Fchain 336–518 (i.e., SARS-CoV-2 S-RBD) were used in the MD simulation; and for 6VW1.pdb, the dimers of B-chain (i.e., the PD of ACE2) (with Zn.2+ 703) and F-chain 331–527 (i.e., SARS-CoV-2 S-RBD) were used in the MD simulation. The simulation methods are the same as all the above models. We denote the S-ACE2 bindings as the 6M17-spike-ACE2-binding-model-5 and the 6VW1-spike-ACE2binding-model-6, respectively. The MD data of trajectories can be downloaded under the Creative Commons Attribution 4.0 International Public License from [321], and the data IDs are 11021566 (6VXX.pdb), 11021571 (6VYB.pdb), 10875754 (1R4L.pdb), 10875753 (1R42.pdb), 10905033 (6M17.pdb), and 10875775 (6VW1.pdb), respectively, for the six models. In the below, (i) firstly, all these PDB entries will be optimized into a much more stable transition state—the hybrid strategy [405] of mathematical optimization’s neighboring different (local search) algorithms is used in the optimization; (ii) secondly, we will present some important structural bioinformatics from the optimized structures; and (iii) we then only prove the structural bioinformatics of
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(ii) from the analyses of the MD data of [321] (in order to reduce the numerously large structural bioinformatics obtained from the MD data). Currently, lots of researchers are using optimization to screen, find, and design new therapies for COVID-19 but it is not always used professionally. The hybrid strategy of mathematical optimization’s neighboring different (local search) algorithms is used professionally in this chapter. Basing on this optimization approach, we will catch some basic structural bioinformatics. The optimized structure is at a transition state with the best stability and the lowest energy. To really understand the stability of molecules and their mechanisms of action, we should consider not only the static NMR, X-ray, or cryo-EM structures concerned but also the dynamical information obtained by MD or quantum mechanics/molecular mechanics (QM/MM) simulating their internal motions or dynamic processes. We will just use and analyze the MD trajectory data of others to confirm our optimizationbased structural bioinformatics. We can get numerously large bioinformatics from the large-scale MD or QM/MM raw trajectory data. The optimization strategy will significantly reduce the scale of data and at the same time get rid of useless bioinformatics. The structural bioinformatics approach used here is also quite appealing for studying various in-depth biological phenomena. Although currently, the MD trajectory data is already present, X-ray or cryo-EM experimental structures are also available, interaction profiling is also performed by the data collectors, and many aspects are still needed for the author to study further; for example, the spike experimental structures are not complete (so that the trajectory data DESRES-ANTON-10897136 and DESRES-ANTON-10897850 (released on March 27, 2020) are without additional loop structures and glycan chains) and many other spike molecular modeling (MM) models around the world are not definitely complete and correct yet. Thus, currently, we still need to deeply analyze the many spike MM models and their MD trajectory data around the world. The MD trajectory data of the six models is huge. We focus on/represent them into six optimized structures; and we only confirm their structural bioinformatics from the analyses of the huge collected MD trajectory data. The representation is clear and scientific, because only the optimized structures are the most stable ones and with lowest energies. Our optimization strategy might be the most correct and professional one, because many people are using optimization to screen compounds now but almost all failed in the clinical drug tests. The noncovalent interactions of hydrogen bonds (HBs), salt bridges (SBs), and van der Waals (vdWs) contacts and hydrophobic interactions (HYDs) are driving a protein to be able to perform its biological functions. This chapter will find out the HBs, SBs, HYDs, and vdWs of each model from the large MD trajectory data and evaluate the reliability of the MD trajectory data, presenting basic structural bioinformatics (Figs. 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 7.10, 7.11 and 7.12) to drug designers or discovery. We will not aim to design a drug against the COVID-19 virus in this chapter because designing a drug takes a long time and it takes 8 or 10 years to have a successful clinical test.
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7.3 Results and Discussions 7.3.1 The 6VXX (SARS-CoV-2 S Close) Model: Model1 We optimized the A-chain of 6VXX.pdb and got an optimized structure (denoted as 6VXX-Achain-Optimized ) with 5.923734 Å of RMSD (root mean square deviation) value from its original structure. For the 6VXX-Achain-Optimized structure, we found 20 SBs: ASP467-ARG454, ASP53-LYS195, ASP389-LYS528, ASP398-ARG355, GLU1031-ARG1039, ASP820-ARG815, ASP442-ARG509, GLU725-HIS1064, GLU583-LYS535, ASP228-LYS202, GLU96-ARG190, GLU324-LYS537, ASP820-LYS811, ASP663-LYS310, GLU773-ARG1019, ASP775-LYS733, GLU340-LYS356, ASP578-ARG328, ASP574-LYS557, ASP40-ARG44; 140 HBs; 5 .π -cations, TYR396-ARG.+ 355.NH2, ARG.+ 355.NH2PHE464, LYS.+ 1028.NZ-PHE1042, LYS.+ 278.NZ-PHE306, and ARG.+ 44.NH2HIS49; 19 .π -.π stackings, TYR1110-PHE1075, TYR1067-PHE906, PHE800PHE898, PHE898-PHE802, PHE802-PHE1052/PHE927, TYR660-TYR695, HIS655-PHE643, TYR612-PHE318, PHE275-PHE58, PHE92-TRP104 (2), PHE201-PHE106, HIS519-PHE565, PHE423-TRP353 (2), PHE377-TYR369, TRP436-PHE374, and PHE338-TYR365; and its Poison-Boltzmann electrostatic potential surface, hydrophobic/hydrophilic surface, Ramachandran plot, phi, psi, secondary structure, SASA (solvent accessible/accessibility surface area) etc.; we know that NAGs have positive electrostatics, there is a large hydrophobic hole under the .α-helices around GLY744-VAL1040 (where GLY889-ALA890GLY891-ALA892-ALA893 construct a hydrophobic core), and residues TYR904-ARG905-PHE906 construct one solvent accessible surface, etc. For the 10 .μs MD simulation trajectory data [321], there are 8335 frames and each frame has 1.2 ns MD. We picked up 835 frames with a frame interval of 12 ns. From the 835 frames, we can confirm all the above SBs except for the very weak SBs ASP467-ARG454, GLU725-HIS1064, ASP228-LYS202, and ASP663-LYS201; in addition, we find SBs A:GLU1031-B:ARG1039, B:GLU1031-C:ARG1039, C:GLU1031-A:ARG1039, A:ASP574-C:LYS854, B:ASP574-A:LYS854, and C:GLU773-A:LYS974 are among the three monomers of the trimeric spike. The SBs have an oxygen-nitrogen cutoff of 3.2 Å, and in all we found 537 SBs from the 835 frames and we have shown the above SBs in Fig. 7.7. From the 835 frames, for HBs we set 3.0 Å as the donor-acceptor cutoff distance and 20.◦ as the cutoff angle and find 13,817 HBs during the 10 .μs MD; all the 140 HBs of the 6VXX-Achain-Optimized model can be confirmed and we list the HBs with more than 50% occupancy rates during the 10 .μs MD simulations for the 6VXX-trimeric-spike-closed-model-1 in Table 7.1. All the abovementioned SBs are polar contacts (SB and HB) and the SB ASP442-ARG509 has strong HB contacts: C:ASP442.OD1-C:ARG509.NE (during 28–834 frames with an average value of 2.860864 Å) with an occupancy rate of 54.13% and B:ASP442.OD1B:ARG509.NH2 (during the whole 835 frames with an average value of 2.848252 Å) with an occupancy rate of 53.45% (Table 7.1 and Fig. 7.13)—the strong polar
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contact between ASP442 and ARG509 is in the RBD (receptor-binding domain) region of spike, with the polar contact GLU1031-ARG1039 on another side of the spike (central helix-connector domain (CH-CD)), holding the trimeric spike at both ends tightly. From Table 7.1, we know some strong HBs among A-B-Cchains: B:PHE43.N-C:PHE565.O (during the whole 835 frames with an average value of 2.919316 Å) with an occupancy rate of 54.13%—with a strong side-chain .π − π stacking too (Fig. 7.13), C:TYR369.OH-A:THR415.OG1 (during 83–834 frames with an average value of 3.650197 Å during the whole 835 frames) with an occupancy rate of 50.30% (Fig. 7.13). For the MD, from the performances of the MD secondary structures, RMSD, potential energies, kinetic energies, and RMSF developments, we know that it reached equilibration and it is in a production phase, where RMSF is the RMS (root mean square) fluctuation—the segments 68–78, 142–152, 180–186, 244–261, 622–636, 677–787, and 833–853 of the 6VXX-trimeric-spike-closed-model-1 have larger RMSF values than other regions.
7.3.2 The 6VYB (SARS-CoV-2 S with One SB Open) Model: Model2 We optimized the A-chain of 6VYB.pdb and got an optimized structure (denoted as 6VYB-Achain-Optimized ) with an RMSD value of 6.182470 Å from its original structure. For the 6VYB-Achain-Optimized structure, we found 20 salt bridges (SBs), ASP820-ARG815, ASP578-ARG328, ASP820LYS811, ASP442-ARG509, ASP467-ARG454, ASP53-LYS195, ASP663-LYS310, GLU583-LYS535, ASP775-LYS733, GLU773-ARG1019, GLU340-LYS356, ASP574-LYS557, ASP40-ARG44, GLU1031-ARG1039, GLU725-HIS1064, ASP1084-LYS1086, ASP571-ARG567, ASP405-ARG403, GLU465-ARG457, GLU191-ARG34 (without ASP389-LYS528, ASP398-ARG355, GLU324LYS537, GLU96-ARG190, and ASP228-LYS202 of the 6VXX-Achain-Optimized structure), 264 hydrogen bonds (HBs); 7 .π -cations, TYR396-ARG.+ 355.NH2, ARG.+ 355.NH2-PHE464, LYS.+ 1028.NZ-PHE1042, LYS.+ 278.NZ-PHE306, ARG.+ 44.NH2-HIS49, ARG.+ 466.NH2-TRP353, and LYS.+ 1073.NZ-PHE1075; 17 .π − π stackings, TYR1110-PHE1075, PHE800-PHE898, PHE898-PHE802, PHE802-PHE1052/PHE927, TYR660-TYR695, PHE92-TRP104 (2), PHE201PHE106, PHE423-TRP353 (2), PHE377-TYR369, TRP436-PHE374, PHE58PHE275, TYR495-TYR453, PHE515-PHE392, PHE192-TRP104 (without TYR1067-PHE906, HIS655-PHE643, TYR612-PHE318, HIS519-PHE565, and PHE338-TYR365 of the 6VXX-Achain-Optimized structure); and its PoisonBoltzmann electrostatic potential surface, hydrophobic/hydrophilic surface, Ramachandran plot, phi, psi, secondary structure, SASA, etc.—we know that the NAGs have positive electrostatics, there is a large hydrophobic hole under the .α-helices around GLY744-VAL1040 (where GLY889-ALA890-GLY891-ALA892-
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ALA893 and GLY667-ALA668-GLY669 construct two respective hydrophobic cores), and residues TYR904-ARG905-PHE906 and ARG355-LYS356-ARG357 construct two respective solvent accessible surfaces, etc. From the 835 frames (with a frame interval of 12 ns) of the 10 .μs MD simulation trajectory data [321], we can confirm all the above 20 SBs except for GLU725-HIS1064; in addition, we find SBs (1) A:GLU1031B:ARG1039, B:GLU1031-C:ARG1039, and C:GLU1031-A:ARG1039 (with weak SBs A:GLU1031-B:LYS1038, B:GLU1031-A:LYS1038, and C:GLU1031A:LYS1038), (2) C:ASP574-B:LYS854, and (3) B:GLU773-C:ARG1014 among the three monomers of the trimeric spike. In all we found 556 SBs and have shown the above SBs in Fig. 7.8. We found 13,652 HBs during the 10 .μs MD; all the 264 HBs of the 6VYB-Achain-Optimized model can be confirmed and we list the HBs with more than 50% occupancy rates during the 10 .μs MD simulations for the 6VYB-trimeric-spike-opened-model-2 in Table 7.2. All the abovementioned SBs are polar contacts and the SB ASP442-ARG509 has strong HB contacts: B:ARG509.NE-B:ASP442.OD2 with an occupancy rate of 58.44% (during the whole 835 frames with an average value of 2.826612 Å) and B:ARG509.NH2B:ASP442.OD1 with an occupancy rate of 51.62% (during the whole 835 frames with an average value of 2.827929 Å) (Table 7.2 and Fig. 7.14)—the polar contact between ASP442 and ARG509 is in RBD of spike, with the polar contacts GLU1031-ARG1039 and GLU1031-LYS1038 in the CH-CD of the spike, holding the trimeric spike at both ends tightly. From Table 7.2, we know some strong HBs among A-B-C-chains: A:PHE43.N-B:PHE565.O (Fig. 7.14) with an occupancy rate of 51.38% (during the whole 835 frames with an average value of 2.937867 Å), B:PHE43.N-C:PHE565.O (Fig. 7.14) with an occupancy rate of 54.01% (during the whole 835 frames with an average value of 2.933415 Å), and C:PHE43.NA:PHE565.O (Fig. 7.14) with an occupancy rate of 54.37% (during the whole 835 frames with an average value of 2.911408 Å)—between the side-chains of PHE43 and PHE565, there are strong .π -.π stackings too. For the MD, from the performances of the MD secondary structures, RMSD, potential energies, kinetic energies, and RMSF developments, we know it reached equilibration and it is in a production phase. The RMSF values show us that the segments 68–78, 142–152, 181–184, 247–257, 477–487, 622–635, 677–687, 842– 844, 941–944, and 1140–1148 of the 6VYB-trimeric-spike-opened-model-2 have larger RMSF values than other regions. For the above two (closed and opened) spike models, we may see in each monomer that there is a strong polar contact between ASP442 and ARG509, and there is a strong HB (at the same time, a .π − π stacking) between PHE43.N and PHE565.O among the three monomers.
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7.3.3 The 1R4L (ACE2 Close) Model: Model3 We optimized 1R4L.pdb and got an optimized structure (denoted as 1R4Loptimized ) with an RMSD value of 0.961113 Å from its original structure. For the 1R4Loptimized structure, we found 18 SBs, GLU406-ARG518, GLU402ARG514, GLU181-ARG177, GLU406-HIS374, GLU433-LYS288, GLU232ARG582, ASP30-HIS34, GLU310-ARG306, ASP201-ARG219, ASP206LYS562, GLU457-ARG460, GLU182-ARG115, GLU435-LYS541, GLU479LYS475, GLU208-ARG219, GLU22-LYS26, GLU145-LYS363, and GLU402HIS374; 50 HBs; 10 .π -cations, TRP48-ARG357.NE (2), TRP302-ARG306.NE, TRP215-LYS577.NZ, ARG514.NE-TYR515, TYR515-ARG273.NE, TRP461ARG204.NE, TYR497-LYS174.NZ, TRP478-LYS481.NZ, and TRP165-ARG169. NH2; 22 .π -.π stackings, PHE72-TRP69, TRP349-TRP48 (3), TRP328-PHE327, PHE314-HIS417, HIS265-TYR158, TYR158-TYR255, TRP473-TRP459, (3) TRP459-TRP477, TRP477-TRP478 (2), PHE230-TYR454, TYR202-TYR196, PHE504-HIS345, HIS345-HIS505, HIS505-PHE512, HIS401-HIS378, HIS378HIS374, and HIS374-Zn2.+ , Zn2.+ -HIS378; and its Poison-Boltzmann electrostatic potential surface, hydrophobic/hydrophilic surface, phi, psi, secondary structure, SASA, ligand (XX5 804) interaction diagram, and Ramachandran plot (Fig. 7.1). We can see that the Ramachandran plot has a dark area, in SASA graph the SER411-ALA412-ALA413 area is highly hydrophobic, and there are three most solvent accessible areas: TYR202-TRP203-ARG204, TRP459-ARG460-TRP461, and ARG514-TYR515-TYR516 (where the HB TYR516.OH-THR229.OG1 has an occupancy rate of 53.05% during the 10 .μs MD (Table 7.3)).
Fig. 7.1 The ligand (XX5 804) interaction diagram and the Ramachandran plot of the 1R4Loptimized model
From the 8335 frames (with a frame interval of 1.2 ns) of the 10 .μs MD trajectory data [321], we get 146 SBs and we can confirm all the 15 SBs except for the ones (GLU406-HIS374, ASP30-HIS34, GLU402-HIS374)
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with HIS residues—these three SBs are replaced by SBs GLU406-ARG518, ASP30-LYS26/31, and GLU402-ARG514/518; some strong SBs such as GLU435LYS541, GLU182-ARG115, ASP206-LYS562, ASP201-ARG219, GLU22-LYS26, GLU208-ARG219, GLU433-LYS288, and GLU406-ARG518 are shown in Fig. 7.9. From the 8335 frames, we got 4033 HBs and all the 50 HBs in the 1R4Loptimized structure can be confirmed from them, and we list the HBs with more than 50% occupancy rates in Table 7.3, where TYR237.OH-VAL485.O (with an average value of 2.907522 Å and broken during frames 103–169 and 211–235 with a frame interval of 12 ns), TYR252.OH-LEU156.O (with an average value of 3.143333 Å and broken during frames 1–32, 103–202, 272–279, and 380–404 with a frame interval of 12 ns), and THR516.OH-THR229.OG1 (with an average value of 2.921907 Å) (Fig. 7.15) span 248, 96, and 287 residues, respectively. For the MD, the RMSD values from the 2600th frame equilibrate around 3.5 Å and the whole RMSD values of 8335 frames vary within 2 Å—this implies that the MD is very reliable; the secondary structural changes happened in the region around ALA36 unfolding from .α-helices to turns starting from the 3700th frame, in the region around VAL172 unfolding from .α-helices to turns even starting from beginning, and in the region around PHE274 even starting from the .α-helices to the 3.10 -helices; and for the RMSF values, the THR129-GLN139 region has large RMSF values from the 1600th frame, the region around PRO289 has large RMSF values from the 5050th frame, and the C-terminal THR609-ASP615 has large RMSF values even since the beginning of MD.
7.3.4 The 1R42 (ACE2 Open) Model: Model4 We optimized 1R42.pdb and get an optimized structure (denoted as 1R42optimized ) with an RMSD value of 0.978346 Å from its original structure. For the 1R42optimized structure, we found 18 SBs, GLU181-ARG177, GLU433LYS288, GLU310-ARG306, ASP201-ARG219, GLU182-ARG115, GLU208ARG219, GLU402-HIS374, GLU37-ARG393, ASP355-ARG357, GLU231LYS234, GLU495-ARG177, GLU489-ARG482, GLU430-LYS541, ASP509LYS187, GLU402-HIS378, GLU227-LYS458, GLU189-LYS112, and ASP543HIS417 (without the SBs GLU406-ARG518, GLU402-ARG514, GLU406HIS374, GLU232-ARG582, ASP30-HIS34, ASP206-LYS562, GLU457-ARG460, GLU435-LYS541, GLU479-LYS475, GLU22-LYS26, and GLU145-LYS363 of the 1R4Loptimized structure); 230 HBs; 13 .π -cations, ARG306.NE-TRP302, ARG357.NE-TRP48 (2), LYS577.NZ-TYR215, ARG514.NE-TYR515, TYR515ARG273.NE, ARG204.NE-TRP461 (2), ARG169.NE-TRP165, LYS174.NZTYR494, LYS309.NZ-TYP328, LYS288.NZ-PHE285, and LYS441.NZ-TYR279 (without TRP478-LYS481.NZ of the 1R4Loptimized structure); 29 .π -.π stackings, PHE390-PHE40, PHE40-TRP69, TRP48-TRP349 (2), PHE327-TRP328 (2), HIS373-PHE314, PHE314-PHE315, HIS374-HIS378, HIS378-HIS401, HIS401-TYR385/TYR381, PHE400-PHE525, TYR587-PHE588, TRP566-
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TYR217, TYR515-HIS505, HIS505-PHE504/PHE512, TYR196-TYR202, PHE464-TYR199, TYR594-TYR243, TYR255-TYR158, TYR158-HIS265, HIS493-TYR497, (2) TRP459-TRP477, TRP477-TRP478 (2), and TRP473TRP459 (without PHE72-TRP69, PHE314-HIS417, and PHE230-TYR454 of the 1R4Loptimized structure); and its Poison-Boltzmann electrostatic potential surface, hydrophobic/hydrophilic surface, secondary structure, phi, psi, SASA, etc. We know that in the SASA graph the SER411-ALA412-ALA413 area is highly hydrophobic and there are three most solvent accessible areas: TYR202-TRP203-ARG204, TRP459-ARG460-TRP461, and ARG514-TYR515-TYR516 (where there is a HB TYR516.OH-THR229.OG1 with an occupancy rate of 52.27% during the 10 .μs MD). From the 8335 frames (with a frame interval of 1.2 ns) of the 10 .μs MD trajectory data [321], we get 134 SBs and we can confirm all the 15 SBs except for the ones (ASP543-HIS417, GLU402-HIS374/378) with HIS residues—these three SBs are replaced by SBs ASP543-LYS416/419/534/541 and GLU402-ARG514/518; some strong SBs such as GLU182-ARG115, ASP201-ARG219, GLU208-ARG219, ASP355-ARG357, GLU231-LYS234, GLU489-ARG482, GLU227-LYS458, and GLU189-LYS112 are shown in Fig. 7.10. From the 8335 frames, we got 4340 HBs and all the 230 HBs in the 1R42optimized structure can be confirmed from them, and we list the HBs with more than 50% occupancy rates in Fig. 7.4, where TYR237.OH-VAL485.O (with an average value of 2.827859 Å), THR567.OG1TYR215.O (with an average value of 2.824532 Å), and THR516.OH-THR229.OG1 (with an average value of 2.940768 Å) (Fig. 7.16) span 248, 352, and 287 residues, respectively (where there is a .π -cation TYR215-LYS577.NZ), and from Tables 7.3 and 7.4 and Figs. 7.15 and 7.16, we know that both 1R42-ACE2-closed-model-4 and 1R4L-ACE2-opened-model-3 have three very strong HBs THR229.OG1ASP225.O (with occupancy rates of 61.90 and 66.27%, during the whole 835 frames (with a frame interval of 12 ns) with average values of 2.835496 and 2.803843 Å), THR371.OG1-ASP367.O (with occupancy rates of 61.73 and 61.87%, during the whole 835 frames with average values of 2.726547 and 2.725134 Å), and HID241.N-TYR237.O (with occupancy rates of 58.96 and 61.37%, during the whole 835 frames with average values of 2.818753 and 2.832368 Å). We can see that the three residues, i.e., TYR237, THR229, and TYR215, play an important role. For the MD, the RMSD values for all the 8335 frames equilibrate around 3.3 Å and the whole RMSD values of 8335 frames vary within 2 Å—this implies that the MD is very reliable; the secondary structural changes happened in the region around PHE274, starting from .α-helices to 3.10 -helices; in the region around GLN325, unfolding from .α-helices to turns; in the region around PHE512, unfolding from .α-helices to turns or 3.10 -helices; and in the region around NAG546-SER563, unfolding from .α-helices to turns or 3.10 -helices from the 6850th frame; and for the RMSF values, the GLU329-TRP349 region, the region around PRO289, and the C-terminal THR609-ASP615 have large RMSF values even since the beginning of MD. For the human ACE2, we found that strong HBs, i.e., TYR237.OH-VAL485.O, THR516.OH-THR229.OG1, TYR252.OH-LEU156.O, and THR567.OG1-
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TYR215.O (where there is a .π -cation, TYR215-LYS577.NZ), have large spans of residues, and three very strong HBs, THR229.OG1-ASP225.O, THR371.OG1ASP367.O, and HID241.N-TYR237.O, have large occupancy rates; thus, we may see that the three residues, TYR237, THR229, and TYR215, play an important role.
7.3.5 The 6M17 (B0 AT1) Model: Model5 We optimized the DF-chains of 6M17.pdb and got an optimized structure (denoted as 6M17-DFchains-Optimized ) with an RMSD value of 3.281984 Å from its original structure. For the 6M17-DFchains-Optimized structure, we found 1 SB, ASP467-ARG457, in the F-chain; 22 SBs in the D-chain, ASP719-ARG708, GLU182-ARG115, ASP335-LYS363, GLU406-ARG518, GLU723-ARG621, GLU312-LYS309, GLU375-HIS378, GLU435-HIS540, ASP201-ARG219, GLU310-ARG306, GLU457-ARG460, GLU701-ARG697, GLU208-ARG219, GLU430-LYS419, GLU181-ARG177, GLU495-ARG177, GLU433-LYS288, ASP509-LYS187, GLU667-ARG644, GLU37-ARG393, GLU189-LYS112, and GLU402-HIS378; 28 hydrogen bonds (HBs); 8 .π -cations, TRP168-LYS.+ 174.NZ, TRP165-ARG.+ 169.NH2, TYR515-ARG.+ 273.NH2, TRP48-ARG.+ 357.NH2, PHE592-LYS.+ 596.NZ, TYR41-LYS.+ 353.NZ, and TRP461-ARG.+ 204.NH2 (2); 24 .π -.π stackings, TYR423-TRP353 (2), TRP566-TYR217, TYR521PHE400, TYR381-TYR385, TYR202-TYR196, TYR199-PHE464, HIS239PHE592, PHE588-TYR587, TRP349-TRP48, TRP328-PHE327, TYR497HIS373, TYR255-TYR158-HIS265, PHE681-PHE643, (2) TRP459-TRP477, TRP477-TRP478 (2), PHE314-PHE315, HIS505-PHE504/PHE512/TYR515, and HIS378-HIS374; and its Poison-Boltzmann electrostatic potential surface, hydrophobic/hydrophilic surface, secondary structure, SASA, etc. We know that residues F:NAG, F:LEU387, F:ALA435, D:GLN728 have positive electrostatics; residue TYR459-ARG460-TRP467 in the D-chain constructs one solvent accessible surface; and F-chain residues SER371-ALA372-SER373, ALA411-PRO412-GLY413, and ALA475-GLY476-SER477-THR478-PRO479 and D-chain residues GLY104-SER105-SER106, THR334-ASP335-PRO336GLY337, SER411-ALA412-ALA413, VAL485-GLY486-VAL487-VAL488, PRO500-ALA501-SER502, VAL685-THR667-ALA687-PRO688, GLY732PRO733-PRO734, and PRO737-PRO738-VAL739-SER740 construct hydrophobic cores, etc. For the 10 .μs MD simulation trajectory data [321], there are 8335 frames and each frame has 1.2 ns MD. From the 8335 frames, we got 188 SBs; we can confirm the SBs in the F-chain (i.e., the RBD of spike), the D-chain (i.e., the PD of human ACE2, especially the following SBs in 1R4L-ACE2-closed-model3 and 1R42-ACE2-opened-model-4 (Figs. 7.9, 7.10 and 7.11): GLU182-ARG115, ASP201/GLU208-ARG219, GLU406-ARG518, GLU435-LYS541, GLU310-ARG306, GLU181ARG177, GLU433-LYS288, and GLU189-LYS112), and between the F-chain and D-chain
of the 6M17-DFchains-Optimized model, and some important SBs have been
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shown in Fig. 7.2, where we know that the SB D:ASP30-F:LYS417 is very strong, but SBs D:GLU23-F:LYS458 (where the .α-helix HB D:GLU23.O-D:THR27.OG1 has an occupancy rate of 54.57%, with an average value of 2.859609 Å during the whole 835 frames), D:GLU37-F:ARG403, and F:GLU484-D:LYS31 do not always exist during the 10 .μs of MD, and for the SB D:ASP38-F:ARG403, we just find one snapshot at the 5681st frame. From the 8335 frames, we found 4987 HBs but we cannot find a strong HB being always kept during the 10 .μs between D- and F-chains: D:LYS31.NZ-F:GLU484.OE1 (0.89%), D:LYS31.NZ-F:GLU484.OE2 (0.74%), D:LYS31.NZ-F:GLU484.CD (0.01%); F:LYS458.NZ-D:GLN24.OE1 (0.01%), F:LYS458.NZ-D:GLU23.OE1 (0.47%), F:LYS458.NZ-D:GLU23.OE2 (0.41%); F:LYS417.NZD:ASP30.OD2 (7.95%), F:LYS417.NZ-D:ASP30.OD1 (8.36%) (Fig. 7.17), F:LYS417.NZD:HIS34.NE2 (3.60%); F:ARG403.NH2-D:HIS34.NE2 (0.04%), F:ARG403.NH1-D:HIS34.NE2 (0.01%), F:ARG403.NH2-D:GLU37.OE2 (3.34%), F:ARG403.NH2-D:GLU37.OE1 (4.56%), F:ARG403.NH1-D:GLU37.OE2 (0.29%), F:ARG403.NH1-D:GLU37.OE1 (0.41%) (Fig. 7.17), and F:ARG403.NH1-D:ASP38.OD1 (0.01%)—where in the brackets are the occupancy
rates during 10 .μs. We list the HBs with more than 50% occupancy rates during the 10 .μs MD simulations for the 6M17-spike-ACE2-binding-model-5 in Table 7.5 and shown in Fig. 7.17. The HB F:THR500.OG1-D:ASP355.OD1 (with an occupancy rate of 53.51%, with an average value of 2.917075 Å during the whole 835 frames) links the spike and the ACE2 strongly. In Fig. 7.17, we have shown four HBs, VAL433.N-LYS378.O (with an occupancy rate of 61%, with an average value of 2.849615 Å during the whole 835 frames), LEU513.N-CYS432.O (with an occupancy rate of 57.08%, with an average value of 2.903840 Å during the whole 835 frames), VAL511.N-ILE434.O (with an occupancy rate of 56.02%, with an average value of 2.904051 Å during the whole 835 frames), and ARG454.N-ASN422.OD1 (with an occupancy rate of 63.83%, with an average value of 2.827907 Å during the whole 835 frames) in the spike; four HBs, THR567.OG1-TYR215.O (with an occupancy rate of 57.78%, with an average value of 2.803045 Å during the whole 835 frames), TYR516.OH-THR229.OG1 (with an occupancy rate of 56.66%, with an average value of 2.881762 Å during the whole 835 frames), TYR41.OH-ASP355.OD1 (with an occupancy rate of 53.47%, with an average value of 2.747765 Åduring frames 85–835), and TYR237.OHVAL485.O (with an occupancy rate of 69.54%, with an average value of 2.803158 Å during the whole 835 frames—where it is broken during frames 41–55, 166–205, and 280–287) in the ACE2; and two polar contacts, F:LYS417.NZ-D:ASP30.OD2/1 and F:ARG403-D:GLU37. For the MD, during the 10 .μs, its RMSD values equilibrate around 3.1 Å and the whole RMSD values of 8335 frames vary within about 2 Å—this implies that the MD is very reliable; the secondary structural developments show us starting from the 2700th frame .α-helix structure of spike ASN360-VAL382 (and human ACE2 VAL488-TYR510) had unfolded into turns, and around LYS288 of human ACE2 starting from the 5660th frame, more turns appear; and the RMSF values show us that the spike PRO337-VAL382 region, human ACE2 ASN134, LEU333, etc. have large RMSF values during the 10 .μs of MD.
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Fig. 7.2 Some important SBs and HBs of the 6M17-spike-ACE2-binding-model-5 confirmed by MD data in [321]
7.3.6 The 6VW1 (Chimera) Model: Model6 We optimized the BF-chains of 6VW1.pdb and got an optimized structure (denoted as 6VW1-BFchains-Optimized ) with an RMSD value of 2.177343 Å from its original structure. For the 6VW1-BFchains-Optimized structure, we found 4 SBs, ASP467-ARG457, GLU465-ARG457, ASP398-ARG355, and ASP442-ARG509 in the F-chain, and 16 SBs in the B-chain, ASP201-ARG219, GLU457-ARG460, GLU495-ARG177, GLU37-ARG393, GLU181-ARG177, ASP509-LYS187, GLU189-LYS112, GLU208-ARG219, ASP499-HIS493, GLU402-HIS374, ASP355-ARG357, GLU489-ARG482, ASP382-HIS401, ASP38-LYS353, GLU406-HIS374, and GLU166-HIS493; 83 HBs (where HB F:TYR449.HH-B:ASP38.OD2 is with distance 1.82 Å); 15 .π -cations, TRP165-ARG169.NE, TRP48-ARG357.NE(2), TRP461-ARG204.NE-TRP271, ARG514.NETYR515-ARG273.NE, TYR380-LYS378.NZ, PHE464-ARG355.NH2, TRP353-ARG466.NE(2),
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TRP302-ARG306.NE(2), TYR279-LYS441.NZ, and TYR215-LYS577.NZ; 27 .π -.π stackings, TYR423-TRP353(2), TYR196-TYR202, HIS505-TYR515, TYR515-PHE512, PHE512HIS505, HIS505-PHE504, (2)TRP477-TRP459, TRP459-TRP477, TRP477-TRP478(2), TRP48-TRP349(2), TYR497-HIS493, HIS265-TYR158, TYR158-TYR255, PHE523-TYR587, TYR587-PHE588, PHE486-TYR83, PHE390-PHE40, TRP459-TRP473, and TRP594-TYR243;
and its Poison-Boltzmann electrostatic potential surface, hydrophobic/hydrophilic surface, secondary structure, SASA, etc.; we know that residues F:GLY431, TRP436, ILE358, ALA397, B:GLU310, GLN325, SER366, ALA372, and NAG712-713 have positive electrostatics, and the F-chain (i.e., RBD of spike) has high psi degrees and low phi degrees. For the 10 .μs MD simulation trajectory data [321], there are 8335 frames with a frame interval of 1.2 ns. From the 8335 frames, we got 147 SBs and 4187 HBs. We can confirm the strong SBs F:ASP398-F:ARG355 and F:ASP442F:ARG509 in the F-chain (i.e., the RBD of spike), the B-chain (i.e., the PD of human ACE2, especially the following SBs in 1R4L-ACE2-closed-model-3, 1R42-ACE2-opened-model-4, and 6M17-spike-ACE2-binding-model-5 (Figs. 7.9, 7.10, 7.11 and 7.12): GLU182-ARG115, GLU208-ARG219, GLU406-ARG518, GLU435LYS541, GLU310-ARG306, GLU433-LYS288, and GLU189-LYS112), and between the F-chain and B-chain of the 6VW1-BFchains-Optimized model, B:GLU329F:ARG439, F:GLU484-B:LYS31, and B:GLU23-F:LYS458 (where the .α-helix HB B:GLU23.O-B:THR27.OG1 has an occupancy rate of 50.81%, with an average value of 2.858096 Å during the whole 835 frames), and some important SBs have been shown in Fig. 7.3, where we know that the SB B:GLU329-F:ARG439 is very strong, F:GLU484-B:LYS31 is weaker, and SB B:GLU23-F:LYS458 is the weakest, but here the strong .α-helix HB B:GLU23.O-B:THR27.OG1 is found with an occupancy rate of 50.81%, with an average value of 2.858096 Å during the whole 835 frames. From the 8335 frames, we found 4187 HBs and we found two strong HBs being always kept during the 10 .μs between B- and F-chains (Fig. 7.18): F:ARG439.NH1-B:GLU329.OE1 (19.47%), F:ARG439.NH2-B:GLU329.OE2 (19.98%), F:ARG439.NH1-B:GLU329.OE2 (18.68%), F:ARG439.NH2-B:GLU329.OE1 (19.56%), F:TYR449.OH-B:ASP38.OD1 (30.47%), and F:TYR449.OH-B:ASP38.OD2 (29.02%); we also found a very weak HB between B- and F-chains: B:LYS31.NZ-F:GLU484.OE1 (0.65%), B:LYS31.NZ-F:GLU484.OE2 (0.84%), and B:LYS31.NZ-F:GLU484.CD (0.01%), where in the
brackets are the occupancy rates during 10 .μs. We list the HBs with more than 50% occupancy rates during the 10 .μs MD simulations for the 6VW1-spike-ACE2binding-model-6 in Table 7.6 and shown in Fig. 7.18.
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Fig. 7.3 Some important SBs of the 6VW1-spikeACE2-binding-model-6 confirmed by MD data in [321]
In Fig. 7.18, we have shown six HBs, VAL433.N-LYS378.O (with an occupancy rate of 55.27%, with an average value of 2.868132 Å during the whole 835 frames), LEU513.N-CYS432.O (with an occupancy rate of 58.81%, with an average value of 2.865653 Å during the whole 835 frames), VAL511.N-ILE434.O (with an occupancy rate of 53.86%, with an average value of 2.921195 Å during the whole 835 frames), ARG454.N-ASN422.OD1 (with an occupancy rate of 69.92%, with an average value of 2.814954 Å during the whole 835 frames), ASP398.NVAL512.O (with an occupancy rate of 54.78%, with an average value of 2.920962 Å during the whole 835 frames), and LEU461.N-ASP420.O (with an occupancy rate of 50.53%, with an average value of 2.900633 Å during the whole 835 frames) in the spike; four HBs, THR567.OG1-TYR215.O (with an occupancy rate of 59.34%, with an average value of 2.913999 Å during the whole 835 frames, broken during frames 204–206 and 705–723), TYR516.OH-THR229.OG1 (with an occupancy rate of 54.91%, with an average value of 2.912548 Å during the whole 835 frames), TYR41.OH-ASP355.OD2 (with an occupancy rate of 64.94%, with an average
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value of 2.715280 Å during the whole 835 frames), and TYR243.OH-THR282.O (with an occupancy rate of 50.08%, with an average value of 2.791970 Å during the whole 835 frames—where it is broken during frames 86–89, 547–553, and 166– 205) in the ACE2; and the strong HBs, F:ARG439.NH1/2-B:GLU329.OE1/2 and F:TYR449.OH-B:ASP38.OD1/2 between the spike and the ACE2. For the MD, during the 10 .μs starting from about 1900th frame, RMSD values equilibrate around 3.3 Å and the whole RMSD values of 8335 frames vary within about 2 Å—this implies that the MD is very reliable; the secondary structural developments show us that starting from the 1920th frame, .α-helix structure of human ACE2 around the HIS195 region had unfolded into turns, and around GLY173 of human ACE2 and the N-terminal 331–350 region, both have slightly changed into turns from .α-helices and changed back to .α-helices; and the RMSF values of human ACES show us that the regions of 129–139 and 329–335 and Cterminal 612–614 have large RMSF values during the 10 .μs of MD. For the bindings of spike (denoted as F-chain) and human ACE2 (denoted as D/B-chain), polar contacts F:LYS417-D:ASP30, F:ARG403-D:GLU37, F:ARG439B:GLU329, and F:TYR449-B:ASP38 and HB F:THR500.OG1-D:ASP355.OD1 are strong during MD of 10 .μs, salt bridges (SBs) F:LYS458-D/B:GLU23 (but D/B:GLU23 has high HB occupancy rates with D/B:THR27), F:ARG403D/B:GLU37 (has low HB occupancy rates), F:GLU484-D/B:LYS31, and F:ARG403-D/B:ASP38 (but HB D/B:ASP38-F:TYR449 is strong) are weak during the whole 10 .μs; during the whole 10 .μs, in the spike SBs F:ASP398-F:ARG355, and F:ASP442-F:ARG509 and in the human ACE2 SBs GLU182-ARG115, GLU208-ARG219, GLU406-ARG518, GLU435-LYS541, GLU310-ARG306, GLU433-LYS288, and GLU189-LYS112 are always strong in MD of 10 .μs. For HBs, during the whole 10 .μs, in the spike VAL433.N-LYS378.O, LEU513.NCYS432.0, VAL511.N-ILE434.O, and ARG454.N-ASN422.OD1 and in the ACE2 THR567.OG1-TYR215.O, TYR516.OH-THR229.OG1, and TYR41.OHASP355.OD2 are always very strong. The 500 ns MD trajectory data of spikeRBD-and-ACE2 (6M0J.pdb) [99] can confirm the strong polar contact between LYS417 and ASP30 (Fig. 7.4): A:ASP30E:LYS417 (E:LYS417.NZ-A:ASP30.OD2 with an occupancy rate of 43.21% and with an average value of 4.261707 Å during the whole 500 ns, E:LYS417.NZA:ASP30.OD1 with an occupancy rate of 11.58% and with an average value of 3.488454 Å during the whole 500 ns) with an average value of 3.781951 Å during the whole 500 ns. In addition, two weak polar contacts E:GLU484-A:LYS31 (A:LYS31.NZ-E:GLU484.OE1 0.40%, A:LYS31.NZ-E:GLU484.OE2 0.40%), A:GLU23E:LYS458 (E:LYS458.NZ-A:GLU23.OE2 0.40%, E:LYS458.NZ-A:GLU23.OE1 0.40%) are
also found from the analyses of the MD dataset [99]. The top 100 drugs (except for enloplatin) are binding at the interface of SARS-CoV-2-spike-RBD and human ACE2 [100] to disturb the interactions of LYS417 and ASP30 (Table 7.7). The MD trajectory data of [55] (amarolab.ucsd.edu/covid19.php) on the dimer of spike-RBD R-chain binding with human-ACE2 A-chain can also confirm the strong polar contact between LYS417 and ASP30 (Fig. 7.5):
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Fig. 7.4 The strong polar contact (left: SBs, right: HBs) between LYS417 and ASP30 is confirmed by MD data in [99] (PDB template 6M0J)
SBs ACEAA:ASP30-RBDBR:LYS417 and ACECA:ASP30-RBDDR:LYS417 with HBs RBDD:LYS417.NZ-ACEC:ASP30.OD1 21.92%, RBDB:LYS417.NZ-ACEA:ASP30.OD2 20.55%, RBDB:LYS417.NZ-ACEA:ASP30.OD1 15.75%, and RBDD:LYS417.NZ-ACEC:ASP30. OD2 15.75%. The weaker polar contact between GLU484 and LYS31 is also confirmed: SBs RBDBR:GLU484-ACEAA:LYS31 and RBDDR:GLU484-ACECA:LYS31 with HBs ACEC:LYS31.NZ-RBDD:GLU484.OE2 9.59%, ACEA:LYS31.NZ-RBDB:GLU484.OE2 8.9%, ACEC:LYS31.NZ-RBDD:GLU484.OE1 7.53%, and ACEA:LYS31.NZ-RBDB:GLN493. OE1 6.85%. We can confirm the following HBs: RBDD:THR500.OG1-ACEC:ASP355.OD2 43.84% and RBDB:THR500.OG1-ACEA:ASP355.OD2 27.4% . The main SBs and HBs
between the R-chain of spike-RBD-B/D and A-chain of human-ACE2-A/C by analyses of the open MD data in amarolab.ucsd.edu/covid19.php are listed as follows: – The SBs between R-chain of spike-RBD-B/D and A-chain of human-ACE2-A/C:
.·
.· .· .·
.·
.·
.· .· .· .· .· .· .· .· .· .· .·
ACEAA:GLU23-RBDBR:LYS458, ACECA:GLU23-RBDDR:LYS458, . RBDBR:ASP420-ACEAA:LYS26, ACEAA:ASP30-RBDBR:LYS417, ACECA:ASP30-RBDDR:LYS417, RBDBR:GLU484-ACEAA:LYS31, RBDDR:GLU484-ACECA:LYS31, . ACEAA:GLU37-RBDBR:ARG403, ACECA:GLU37-RBDDR:ARG403, . RBDBR:ASP405-ACEAA:ARG393; SBs between chainA of ACEA (i.e., dimeric-ACE monomer-A)—A-chain of ACEC (i.e. dimeric-ACE monomer-C): C:ASP136-A:ARG115, A:ASP136-C:ARG115, A:ASP136-C:LYS174, C:GLU140-A:LYS131, A:GLU140-C:LYS131, C:GLU171-A:LYS131, C:GLU634-A:LYS657, A:GLU634-C:LYS657, A:GLU639-C:ARG710, C:GLU639-A:ARG710, C:GLU667-A:ARG652, A:GLU667-C:ARG652, A:ASP713-C:LYS631, C:ASP713-A:ARG716, A:ASP713-C:ARG716, A:ASP719-C:ARG716, C:ASP799-A:LYS788;
– The HBs (with occupancy rates .≥5%) between spike-RBD-B/D and humanACE2-A/C:
280 .· .· .·
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.·
.· .·
.· .· .·
7 Spike (S) Glycoprotein
RBDD:GLY502.N-ACEC:LYS353.O 50%, RBDB:GLY502.N-ACEA:LYS353.O 25.34%, RBDD:THR500.OG1-ACEC:ASP355.OD2 43.84%, RBDB:THR500.OG1-ACEA:ASP355. OD2 27.4%, RBDD:LYS417.NZ-ACEC:ASP30.OD1 21.92%, RBDB:LYS417.NZ-ACEA:ASP30.OD2 20.55%, RBDB:LYS417.NZ-ACEA:ASP30.OD1 15.75%, RBDD:LYS417.NZ-ACEC:ASP30. OD2 15.75%, RBDD:TYR505.OH-ACEC:GLU37.OE1 17.81%, RBDD:TYR505.OH-ACEC:GLU37.OE2 13.01%, RBDB:TYR505.OH-ACEA:GLU37.OE1 6.16%, RBDB:TYR505.OH-ACEA: GLU37.OE2 6.16%, . ACEA:TYR83.OH-RBDB:ASN487.OD1 37.67%, ACEC:TYR83.OH-RBDD:ASN487.OD1 21.23%, RBDD:TYR489.OH-ACEC:TYR83.OH 13.01% (with .π -.π stacking), ACEC:GLN24.NE2-RBDD:ALA475.O 6.16%, RBDB:TYR473.OH-ACEA:GLN24.OE1 5.48%, ACEA:LYS26.NZ-RBDB:THR415.OG1 5.48%, RBDD:LYS417.NZ-ACEC:ASP30.OD1 21.92%, RBDB:LYS417.NZ-ACEA:ASP30.OD2 20.55%, RBDB:LYS417.NZ-ACEA:ASP30.OD1 15.75%, RBDD:LYS417.NZ-ACEC:ASP30. OD2 15.75%, ACEC:LYS31.NZ-RBDD:GLU484.OE2 9.59%, ACEA:LYS31.NZ-RBDB:GLU484.OE2 8.9%, ACEC:LYS31.NZ-RBDD:GLU484.OE1 7.53%, . ACEA:LYS31.NZ-RBDB:GLN493. OE1 6.85%, RBDD:GLN493.NE2-ACEC:GLU35.OE2 9.59%, RBDB:GLN493.NE2-ACEA:GLU35.OE1 6.85%, RBDD:GLN493.NE2-ACEC:GLU35.OE1 6.85%, RBDD:TYR505.OH-ACEC:GLU37.OE1 17.81%, RBDD:TYR505.OH-ACEC:GLU37.OE2 13.01%, RBDB:TYR505.OH-ACEA:GLU37.OE1 6.16%, RBDB:TYR505.OH-ACEA: GLU37.OE2 6.16%, . RBDD:TYR449.OH-ACEC:ASP38.OD2 7.53%, RBDB:TYR449.OH-ACEA:ASP38.OD1 5.48%, . RBDB:THR500.OG1-ACEA:TYR41.OH 7.53%, RBDD:THR500.OG1-ACEC:TYR41.OH 5.48%, ACEA:TYR83.OH-RBDB:ASN487.OD1 37.67%, ACEC:TYR83.OH-RBDD:ASN487.OD1 21.23%, RBDD:TYR489.OH-ACEC:TYR83.OH 13.01%.
Fig. 7.5 The strong polar contact (left: SBs, right: HBs) between LYS417 and ASP30 is confirmed by MD data in https://amarolab.ucsd.edu/covid19.php ([55]) for dimeric spike-RBDACE2 binding, where for the MD data, the frame stride is 200; thus, we picked up 146 frames in all, and at the picked-up frame numbered 47, its SB distance is 161.388718 Å and its HBs distances are 160.428131 Å and 162.351318 Å (i.e., its SBs and HBs are broken)
The analyses of MD data in https://amarolab.ucsd.edu/covid19.php can also confirm some strong polar contacts, i.e., ASP442-ARG509 and ASP398-ARG355,
7.3 Results and Discussions
281
inside each spike-RBD monomer, and GLU182-ARG115, GLU208-ARG219, GLU435-LYS541, GLU310-ARG306, and GLU433-LYS288 inside each human ACE2 monomer, with the following HBs with occupancy rates .≥5%: – The HBs (with occupancy rates .≥5%) inside the spike-RBD-B/D or inside the human-ACE2-A/C:
.·
.·
.·
.·
.·
.·
.·
RBDD:ARG355.NE-RBDD:ASP398.OD1 36.30%, RBDD:ARG355.NH2-RBDD:ASP398.OD2 34.93%, RBDD:ARG355.NE-RBDD:ASP398.OD2 33.56%, RBDD:ARG355.NH2-RBDD:ASP398.OD1 32.19%, RBDB:ARG355.NH2-RBDB:ASP398.OD2 23.97%, RBDB:ARG355.NE-RBDB:ASP398.OD2 17.12%, RBDB:ARG355.NH2-RBDB:ASP398.OD1 13.7%, RBDD:ARG509.NE-RBDD:ASP442.OD2 61.64%, RBDD:ARG509.NH2-RBDD:ASP442.OD1 52.74%, RBDD:ARG509.NE-RBDD:ASP442.OD1 8.9%, RBDD:ARG509.NH2-RBDD:ASP442.OD2 5.48%, RBDB:ARG509.NE-RBDB:ASP442.OD2 51.37%, RBDB:ARG509.NH2-RBDB:ASP442.OD1 38.36%, RBDB:ARG509.NE-RBDB:ASP442.OD1 17.81%, RBDB:ARG509.NH2-RBDB:ASP442.OD2 15.75%, ACEC:ARG115.NH1-ACEC:GLU182.OE1 33.56%, ACEC:ARG115.NE-ACEC:GLU182.OE2 32.88%, ACEC:ARG115.NE-ACEC:GLU182.OE1 24.66%, ACEC:ARG115.NH1-ACEC:GLU182.OE2 21.92%, ACEA:ARG115.NE-ACEA:GLU182.OE1 31.51%, ACEA:ARG115.NH1-ACEA:GLU182.OE1 29.45%, ACEA:ARG115.NE-ACEA:GLU182.OE2 28.08%, ACEA:ARG115.NH1-ACEA:GLU182.OE2 28.08%, ACEA:ARG219.NH1-ACEA:GLU208.OE2 29.45%, ACEA:ARG219.NH1-ACEA:GLU208.OE1 25.34%, ACEC:ARG219.NH1-ACEC:GLU208.OE1 26.71%, ACEC:ARG219.NH1-ACEC:GLU208.OE2 26.03%, ACEC:ARG518.NE-ACEC:GLU406.OE2 8.22%, ACEC:ARG518.NH1-ACEC:GLU406.OE1 6.85%, ACEC:ARG518.NH1-ACEC:GLU406.OE2 6.85%, ACEC:ARG518.NE-ACEC:GLU406.OE1 5.48%, ACEA:LYS541.NZ-ACEA:GLU435.OE1 32.19%, ACEA:LYS541.NZ-ACEA:GLU435.OE2 25.34%, ACEA:HSE540.NE2-ACEA:GLU435.OE2 23.97%, ACEA:HSE540.NE2-ACEA:GLU435.OE1 8.9%, ACEC:LYS541.NZ-ACEC:GLU435.OE2 31.51%, ACEC:LYS541.NZ-ACEC:GLU435.OE1 24.66%, ACEC:HSE540.NE2-ACEC:GLU435.OE1 13.70%, ACEC:HSE540.NE2-ACEC:GLU435.OE2 13.01%, ACEA:GLU310.N-ACEA:ARG306.O 36.99%, ACEA:ARG306.NE-ACEA:GLU310.OE1 17.12%, ACEA:ARG306.NE-ACEA:GLU310.OE2 8.90%, ACEA:ARG306.NH1-ACEA:GLU310.OE1 5.48%, ACEC:GLU310.N-ACEC:ARG306.O 28.77%, ACEC:ARG306.NE-ACEC:GLU310.OE1 13.70%, ACEC:ARG306.NE-ACEC:GLU310.OE2 12.33%, ACEC:ARG306.NH2-ACEC:GLU310.OE1 5.48%, ACEC:LYS288.NZ-ACEC:GLU433.OE2 41.10%, ACEC:LYS288.NZ-ACEC:GLU433.OE1 27.40%, ACEA:LYS288.NZ-ACEA:GLU433.OE2 18.49%, ACEA:LYS288.NZ-ACEA:GLU433.OE1 12.33%.
7.3.7 Glycans’ Shields Despite the relatively modest contribution of the glycans to the total molecular weight of the spike trimer (17% for the HEK293 glycoform), the glycans shield approximately 40% of the spike protein surface [127] from antibody recognition by glycans, with the notable exception of the human ACE2 RBD. The degree of shielding is largely insensitive to the specific glycoform [127]. Here we will analyze the glycosylated Swiss model MD trajectory (5_Swiss_5_SS.prmtop and 5_Swiss_5_SS_Combined.nc) of SARS-CoV-2 spike glycoprotein with glycans [127, 128] built based on the cryo-EM structure 6VSB.pdb. The HBs (with more than 55.00% occupancy rates) of the MD trajectory are listed as follows: TYR2251.OH-LEU2268.O 77%, TYR11.OH-LEU28.O 75%, THR276.OG1-GLU272.O 74%, TYR1131.OH-LEU1148.O 70%, SER3265.OG-HIE3278.ND1 70%, MET671.N-GLY643.O 68%, LEU2799.NVAL2790.O 67%, TYR2527.OH-GLU2523.O 66%, TYR2305.N-GLY2482.O 66%, LEU2825.N-SER2810.O 66%, THR2516.OG1-GLU2512.O 66%, TYR1185.N-GLY1362.O 65%, THR1040.OG1-LYS1019.O 65%, THR273.OG1PRO269.O 64%, TYR287.OH-GLU283.O 64%, VAL2647.N-LYS2592.O 64%, PHE1486.N-VAL1618.O 64%, PHE2156.N-GLU1819.O 63%, SER2145.OG-HIE2158.ND1 63%, THR3280.OG1-LYS3259.O 62%, SER3030.OGGLN3268.OE1 62%, TYR1407.OH-GLU1403.O 61%, PHE17.N-PHE2779.O 61%, THR3241.OG1-ASN3237.O 61%, ASN893.ND2-VAL889.O 61%, THR2121.OG1-ASN2117.O 61%, ASP552.N-GLU557.O 60%, ILE572.N-ALA583.O
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7 Spike (S) Glycoprotein
60%, CYX645.N-TYR669.O 60%, LEU585.N-SER570.O 60%, PHE2606.N-VAL2738.O 60%, VAL2190.NPHE2197.O 60%, THR1396.OG1-GLU1392.O 59%, LEU1212.N-LYS1223.O 58%, THR1001.OG1-ASN997.O 58%, THR3220.OG1-GLN3216.O 58%, THR2513.OG1-PRO2509.O 58%, SER1025.OG-HIE1038.ND1 58%, GLN3250.NE2-HIE3262.O 58%, THR2171.OG1-PHE2189.O 58%, LEU1705.N-SER1690.O 57%, TYR2955.OHLEU3176.O 57%, ASN2013.ND2-VAL2009.O 57%, ASN902.N-ALA898.O 57%, ILE971.N-ILE967.O 57%, THR857.OG1-ALA853.O 57%, ALA642.N-PRO1957.O 56%, SER2033.OG-GLN2029.O 56%, ASP2792.NGLU2797.O 56%, PHE2257.N-PHE1659.O 56%, ASN2335.N-ARG2316.O 56%, THR3097.OG1-ALA3093.O 56%, VAL2753.N-GLY2764.O 56%, PHE1200.N-LEU1211.O 56%, THR3095.OG1-LEU3091.O 56%, GLU1005.NTHR1001.O 56%, TYR65.N-GLY242.O 55%, ASN2022.N-ALA2018.O 55%, THR1872.OG1-GLN1868.O 55%, PHE3276.N-GLU2939.O 55%, LEU1679.N-VAL1670.O 55%, THR983.OG1-GLN979.O 55%, VAL1456.N-
We also optimized the 5_Swiss_5_SS-6VSB model and got its ligand interactions as presented in Table 7.8 (see Fig. 7.19) to illuminate the recognition by glycans. An “O-Follow-N” rule for the O-glycosylation pattern of SARS-CoV-2 spike protein was revealed in [354].
ASN1428.O 55%.
7.3.8 Spike-Trimer Binding with Nanobody-Nb6c In the website www.rbvi.ucsf.edu/chimerax/data/nanobody-feb2021/, a pdb file “production_Nb6cRBD1.pdb” is presented for “How to View Nanobody Molecular Dynamics in ChimeraX”; this is an MD trajectory file with 600 frames for spiketrimer aa THR2-PRO196, GLN198-SER316, and THR318-PRO512 binding with the nanobody-Nb6c 4YB514-0YB515 and 4YB516-0YB517. We optimized the last frame and got its structural bioinformatics as follows: the optimized spike has 9 .π -.π stackings, PHE11-PHE43, TRP22-TYR92-TRP22, PHE61-PHE184, TYR292TRP306, PHE377-PHE500, PHE385-TYR408-(2), and TRP338 (2)-ARG451.NH2; 8 .π -cations, TYR118-ARG250.NH2+, PHE159-ARG251.NH2+, TYR174-ARG72.NH2+, TYR277ARG216.NH2+, PHE332-LYS341.NZ+, TRP338-ARG451.NH2+-TRP338, and TYR381ARG340.NH2+; 28 SBs, GLU9-LYS25, ASP67-ARG24, ASP74-ARG72, ASP74-ARG77, GLU75-ARG72, ASP96-LYS371, ASP96-LYS93, ASP111-ARG178, GLU134-ARG126, GLU134-LYS131, ASP136-ARG123, ASP136-ARG126, GLU140-ARG123, GLU153-ARG251, ASP259-LYS262, ASP270-LYS273, GLU286-LYS284, ASP287-ARG264, ASP296-ARG242, ASP304-ARG228, GLU325-LYS240, ASP383-ARG340, ASP390-ARG393, GLU391-ARG388, ASP405-LYS409, ASP427-ARG494, ASP452-ARG442, and GLU501-ARG342; and 209 HBs.
The optimal structure has NLN12, THR14, and LEU110 residues binding with 4YB514-0YB515 and GLY145, SER146, LYS240, SER299, PRO300, ALA301, PRO302, GLY303, TYR305, GLY324, PHE327, NLN328, VAL352, and LEU353 residues binding with 4YB516-0YB517. The MD performances show that the RMSD values level off after the 25th frame; the RMSF values have large variations in the loops aa 142–152 and aa 233–243 mainly because turns change into coils during 179–498 frames; the variations of MD secondary structures are mainly in segments aa PRO53-ASP58 and ALA404-TRP406 which has .α-helix changed into .310 -helix from the 520th frame. The MD HBs with more than 10.00% occupancy rates are listed in Table 7.9.
7.4 Concluding Remarks
283
7.3.9 The RGD Motif of Spike-RBD In “the MD-trajectories of SARS-CoV-2-spike-RBD from accelerated molecular simulation” [258], we are told that SARS-CoV-2 spike protein is unlikely to bind to integrins via the ARG70-GLY71-ASP72 RGD motif of the receptorbinding domain. We take 100 as the frame stride and can get 100 frames for “amd2_rbd_glycan.nc,” “amd3_rbd_glycan.nc,” and “amd4_rbd_glycan.nc,” respectively; the MD secondary structural graphs can be seen in Fig. 7.6 where for rep3 around the RGD motif, the .α-helix seems to unfold into .310 -helix completely. The spike residues are labeled with aa ASN1-LYS195 and with a ligand 4YB196-197 binding with spike residues GLY6 and NLN10; we optimized the model and get four .π -interactions: PHE41-TRP103, TYR162-TYR120LYS84.NZ, TRP20-TYR90-TRP20-ARG133.NH2, and PHE131-ARG22.NH2. The MD SBs and HBs can be seen in Tables 7.10, 7.11 and 7.12, where the MD-SBs ARG75/LYS84-AS72-ARG70-GLU73-ARG75/LYS84 are around the RGD motif, and around the RGD motif at residue ARG70, there are HBs, ARG70.NE-GLU73.OE1, ARG70.NE-GLU73.OE2, ARG70.NH1-GLU73.OE1, and ARG70.NH1-GLU73.OE2, during MD-rep2-3-4; at residue GLY71, there is an HB, GLY71.N-GLN173.O, during MD-rep2-3-4; and at residue ASP72, there are HBs, ASP72.N-GLY171.O, ARG75.NH1-ASP72.OD2, and ARG75.NH2ASP72.OD1.
Fig. 7.6 The MD secondary structures of 100 frames (with frame stride .= 10) of aa ASN1LYS195 [258]
7.4 Concluding Remarks Coronavirus SARS-CoV-2 S promote entry into cells and are the main target of antibodies and inhibitors. Human ACE2 is the cellular receptor for SARS-CoV-2 and is an antiviral drug target against SARS-CoV-2. The spike and the human ACE2 clearly are very helpful and useful for revealing secrets of COVID-19 virus and for structure-based drug design or discovery. Fortunately, the molecular structures of SARS-CoV-2 S, human ACE2, and their bindings were already determined and released into the Protein Data Bank (PDB) with PDB entries 6VXX, 6VYB, 1R4L, 1R42, 6M71, and 6VW1, respectively. This chapter perform MD studies of these six structures and present some structural bioinformatics (based on the optimized
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7 Spike (S) Glycoprotein
monomers) for developing therapies of the currently fatal COVID-19 virus. For the trimeric spike, we found (i) a strong polar contact between ASP442 and ARG509 in the receptor-binding domain (RBD) of each monomer (where we found that the compounds megestrol acetate, nitazoxanide, and ritonavir bind with ARG509.NH1 with HB occupancy rates of 0.6%, 17.26%, and 0.6%, respectively, during 2 .μs of MD (Table 7.7)), (ii) strong hydrogen bond (HB) PHE43.N-PHE565.O and their side-chain .π -.π stackings between each two monomers, and (iii) strong polar contacts between GLU1031 and ARG1039/LYS1038 in the central helix-connector domain (CH-CD) between each two monomers; thus, holding the three monomers tightly from both ends to the middle of the spike; in the spike HB C:TYR369.OHA:THR415.OG1 has also a high occupancy rate of 50.30% (where we found the compound tadalafil binds with TYR369.OH with an HB occupancy rate of 1.79% during 2 .μs of MD, and the compounds fluticasone propionate and nebivolol bind with THR415 with an HB occupancy rates of 13.61% and 0.6%, respectively, during 2 .μs of MD (Table 7.7)). We think these compounds broke the strong polar contact ASP442-ARG509 and the strong HB C:TYR369.OH-A:THR415.OG1 so that the spike lost its protein functions. For the human ACE2, we found that the strong HBs TYR237.OH-VAL485.O, THR516.OH-THR229.OG1, TYR252.OH-LEU156.O, and THR567.OG1-TYR215.O (where there is a .π -cation, TYR215-LYS577.NZ) have large spans of residues, and three very strong HBs, THR229.OG1-ASP225.O (with occupancy rates of 61.90 and 66.27%), THR371.OG1-ASP367.O (with occupancy rates of 61.73 and 61.87%), and HID241.N-TYR237.O (with occupancy rates of 58.96 and 61.37%), have large occupancy rates; thus, we may see that the three residues, i.e., TYR237, THR229, and TYR215, play an important role. For the bindings of spike (denoted as F-chain) and human ACE2 (denoted as D/B-chain), polar contacts F:LYS417-D:ASP30, F:ARG439-B:GLU329, and HB F:THR500.OG1-D:ASP355.OD1 are very strong during MD of 10 .μs, and salt bridges (SBs) F:LYS458-D/B:GLU23 (but D/B:GLU23 has high HB occupancy rates with D/B:THR27), F:ARG403-D/B:GLU37 (has low HB occupancy rates), F:GLU484-D/B:LYS31, and F:ARG403-D/B:ASP38 (but HB D/B:ASP38F:TYR449 is strong) are weak during the whole 10 .μs; during the whole 10 .μs, in the spike SBs F:ASP398-F:ARG355 and F:ASP442-F:ARG509 and in the human ACE2 SBs GLU182-ARG115, GLU208-ARG219, GLU406-ARG518, GLU435LYS541, GLU310-ARG306, GLU433-LYS288, and GLU189-LYS112 are always strong in MD of 10 .μs. These MD structural bioinformatics were obtained which are based on the optimized monomer. The MD data of [321] is numerously large; thus, detailed structural bioinformatics will be further studied and presented very soon. By the analyses (Table 7.7) of the 2 .μs MD data of DESRES-ANTON10906555 (6VXX.pdb and 6VW1.pdb)—50 drugs respectively in complex with SARS-CoV-2-trimericspike-RBDs—we know that (1) the compounds alprostadil, AZD-8330, azilsartan, captopril, cefamandole nafate, cefixime, CP195543, darunavir, levomefolate, lometrexol, pelitrexol, raltitrexed, rebamipide, recoflavone, and vorapaxar broke the polar contact F:ARG439-B:GLU329 to make the spike lost its protein functions; (2) the compounds AZD-8330, azilsartan,
7.4 Concluding Remarks
285
levomefolate, lometrexol, pelitrexol, recoflavone, and vorapaxar broke the HB F:THR500.OG1-D:ASP355.OD1 to make the spike lost its protein functions; (3) the compounds aprepitant, calcifediol, clobazam, and terazosin broke the HB F:GLU484-D/B:LYS31 to make the spike lost its protein functions; (4) the compounds megestrol acetate, nitazoxanide, and ritonavir disturbed the strong polar contact F:ASP442-F:ARG509 to make the spike lost its protein functions; (5) the compounds fluticasone propionate and nebivolol made the loss of contacts with F:THR415; and (6) the compound tadalafil broke the HB C:TYR369.OHA:THR415.OG1 to make the spike lost its protein functions. Lastly, we review some literatures to further confirm the findings in this chapter. The SB F:ARG439-B:GLU329 is confirmed in [317, 387]. The SB F:LYS417D/B:ASP30 is confirmed in [13, 21, 123, 248, 336, 353, 376, 428]. In [13] the HB F:TYR449-D/B:ASP38 is also confirmed. The SB F:GLU484-D/B:LYS31 is confirmed in [380]. We wanted to perform deep protein-protein or protein-ligand profiling in terms of interactions and in lieu of the biological functioning of individual proteins or the complexes. We have presented the targeted interaction profiling between different biomolecules as they are operational inside the body. This will provide us more understanding how the spike protein and the ACE2 protein become the main windows in the spread of the COVID-19. Basically, in this chapter, we can find that there is a strong polar contacts between LYS417 of the SARS-CoV-2-spike and ASP30 of the ACE2: our MD and optimization studies showed us that we cannot find it from SARS-CoV-1 and MERS, and even the SARS-CoV-2-D614G mutant will not change it at all. The noncovalent interactions of hydrogen bonds (HBs), salt bridges (SBs), van der Waals (vdWs) contacts, and hydrophobic interactions (HYDs) are driving a protein to be able to perform its biological functions. This chapter presented fundamental and basic bioinformatics of the HBs, SBs, HYDs, and vdWs of each model from the large MD trajectory data and evaluate the reliability of the MD trajectory data of 10 .μs. Clearly, the basic bioinformatics presented in this chapter cannot solve current hard work of COVID-19 problems. A more concrete information and pathway should be determined to provide insights how this virus can be stopped from entering inside the human body. A detailed interaction profile of various inhibitors along with the interaction mechanism of the two proteins can help in understanding why all drugs till now are failing and what precautions we should take in developing any new drug molecule against the deadly disease. Basing on the fundamental bioinformatics of this chapter, we will further study the databases DESRES-ANTON-10906555 and DESERS-ANTON-10918441 of (all the FDAapproved) drugs binding with the SARS-CoV-2 trimeric spike and the ectodomain of human ACE2 in Chaps. 17 and 18. The optimized structure is at a transition state with the best stability and the lowest energy. Currently, a lot of researchers are using optimization to screen and design compounds but they do not definitely use optimization algorithms professionally. The hybrid strategy of mathematical optimization’s neighboring different (local search) algorithms is used professionally in this chapter. Currently
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the spike’s structures are still not complete yet and static molecular structures are not enough to reveal the secrets of COVID-19 virus; MD is still needed. Optimization strategy can also catch main bioinformatics from the huge MD trajectory databases and reduce the large-scale datasets. This chapter studied the MD trajectory databases from the optimization strategies and should have a value to COVID-19 researchers as a reference. For SARS-CoV-2, we also found some interesting results on (monomeric and dimeric) Mpro and PLpro, RdRp, etc. Furthermore, research will be revealing more secrets of the SARS-CoV-2.
Supplementary Information
Table 7.1 The HBs with more than 50% occupancy rates during the 10 μs MD simulations for the 6VXX-trimeric-spike-closedmodel-1
Donor
Acceptor
Occupancy
Cchain-TYR37-Side-OH
Cchain-LEU54-Main-O
75.09%
Achain-TYR37-Side-OH
Achain-LEU54-Main-O
73.05%
Bchain-TYR37-Side-OH
Bchain-LEU54-Main-O
70.78%
Bchain-ARG454-Main-N
Bchain-ASN422-Side-OD1
68.98%
Bchain-TYR91-Main-N
Bchain-GLY268-Main-O
68.26%
Cchain-TYR91-Main-N
Cchain-GLY268-Main-O
65.63%
Cchain-TYR313-Side-OH
Cchain-GLU309-Main-O
65.39%
Bchain-TYR741-Side-OH
Bchain-LEU962-Main-O
65.27%
Achain-THR299-Side-OG1
Achain-PRO295-Main-O
64.31%
Bchain-THR299-Side-OG1
Bchain-PRO295-Main-O
63.23%
Bchain-THR302-Side-OG1
Bchain-GLU298-Main-O
63.23%
Achain-TYR91-Main-N
Achain-GLY268-Main-O
63.23%
Bchain-LEU513-Main-N
Bchain-CYS432-Main-O
62.28%
Cchain-THR883-Side-OG1
Cchain-ALA879-Main-O
61.80%
Cchain-ARG454-Main-N
Cchain-ASN422-Side-OD1
61.32%
Bchain-SER438-Side-OG
Bchain-ASP442-Side-OD2
61.20%
Cchain-LEU455-Main-N
Cchain-PRO491-Main-O
60.72%
Cchain-LEU513-Main-N
Cchain-CYS432-Main-O
60.72%
Bchain-LEU611-Main-N
Bchain-SER596-Main-O
60.60%
Bchain-TYR269-Side-OH
Bchain-PRO85-Main-O
60.36%
Cchain-LEU611-Main-N
Cchain-SER596-Main-O
60.00%
Cchain-LEU585-Main-N
Cchain-VAL576-Main-O
59.52%
Cchain-THR299-Side-OG1
Cchain-PRO295-Main-O
59.16%
Achain-TYR313-Side-OH
Achain-GLU309-Main-O
58.92%
Bchain-ASP398-Main-N
Bchain-VAL512-Main-O
58.80%
Achain-THR881-Side-OG1
Achain-LEU877-Main-O
58.68%
Bchain-TYR451-Side-OH
Bchain-ASP442-Side-OD1
58.68%
Achain-THR302-Side-OG1
Achain-GLU298-Main-O
58.56%
Cchain-VAL433-Main-N
Cchain-LYS378-Main-O
58.44%
Achain-SER112-Side-OG
Achain-GLU132-Main-O
58.44%
Achain-ARG454-Main-N
Achain-ASN422-Side-OD1
58.32%
Bchain-VAL433-Main-N
Bchain-LYS378-Main-O
58.20%
Bchain-LEU455-Main-N
Bchain-PRO491-Main-O
57.84%
Cchain-SER438-Side-OG
Cchain-ASP442-Side-OD1
57.84%
Bchain-SER982-Side-OG
Bchain-ASN978-Main-O
57.49%
Achain-LEU611-Main-N
Achain-SER596-Main-O
57.13%
Cchain-THR302-Side-OG1
Cchain-GLU298-Main-O
57.01%
Achain-LEU513-Main-N
Achain-CYS432-Main-O
56.89%
Bchain-PHE106-Main-N
Bchain-LEU117-Main-O
56.89%
(continued)
Supplementary Information Table 7.1 (continued)
287 Donor
Acceptor
Occupancy
Bchain-THR883-Side-OG1
Bchain-ALA879-Main-O
56.77%
Bchain-GLN1054-Side-NE2
Bchain-PRO1053-Main-O
56.65%
Achain-THR883-Side-OG1
Achain-ALA879-Main-O
56.65%
Bchain-CYS671-Main-N
Bchain-TYR695-Main-O
56.65%
Achain-GLN1054-Side-NE2
Achain-PRO1053-Main-O
56.53%
Achain-SER1003-Side-OG
Achain-GLY999-Main-O
56.53%
Bchain-TYR695-Main-N
Bchain-CYS671-Main-O
56.41%
Bchain-VAL539-Main-N
Bchain-GLY550-Main-O
56.17%
Achain-THR1066-Side-OG1
Achain-LYS1045-Main-O
56.17%
Achain-LEU585-Main-N
Achain-VAL576-Main-O
56.05%
Cchain-TYR269-Side-OH
Cchain-PRO85-Main-O
55.93%
Achain-PHE106-Main-N
Achain-LEU117-Main-O
55.93%
Cchain-PHE1103-Main-N
Cchain-VAL1096-Main-O
55.81%
Achain-HIS1064-Side-ND1
Achain-SER1051-Side-OG
55.81%
Bchain-ALA694-Main-N
Bchain-GLU654-Main-O
55.81%
Bchain-HIS1064-Side-ND1
Bchain-SER1051-Side-OG
55.81%
Achain-VAL511-Main-N
Achain-ILE434-Main-O
55.69%
Achain-ASN777-Main-N
Achain-GLU773-Main-O
55.57%
Bchain-ILE651-Main-N
Bchain-VAL610-Main-O
55.57%
Achain-VAL551-Main-N
Achain-THR588-Main-O
55.57%
Cchain-GLN1054-Side-NE2
Cchain-PRO1053-Main-O
55.45%
Bchain-ILE598-Main-N
Bchain-ALA609-Main-O
55.21%
Bchain-ASN919-Side-ND2
Bchain-VAL915-Main-O
55.09%
Bchain-PHE275-Main-N
Bchain-THR51-Main-O
54.97%
Achain-VAL433-Main-N
Achain-LYS378-Main-O
54.97%
Achain-VAL539-Main-N
Achain-GLY550-Main-O
54.97%
Cchain-ASP398-Main-N
Cchain-VAL512-Main-O
54.97%
Bchain-PHE1089-Main-N
Bchain-PHE1121-Main-O
54.73%
Cchain-ILE651-Main-N
Cchain-VAL610-Main-O
54.61%
Cchain-SER803-Side-OG
Cchain-NLM1172-Side-OD1
54.49%
Bchain-THR1066-Side-OG1
Bchain-LYS1045-Main-O
54.25%
Bchain-VAL511-Main-N
Bchain-ILE434-Main-O
54.13%
Cchain-SER816-Side-OG
Cchain-GLN1054-Side-OE1
54.13%
Bchain-PHE43-Main-N
Cchain-PHE565-Main-O
54.13%
Cchain-ARG509-Side-NE
Cchain-ASP442-Side-OD1
54.13%
Achain-TYR266-Main-N
Achain-ALA93-Main-O
54.01%
Achain-LEU277-Main-N
Achain-HIS49-Main-O
53.89%
Achain-PHE541-Main-N
Achain-GLY548-Main-O
53.77%
Achain-LEU461-Main-N
Achain-ASP420-Main-O
53.77%
Achain-PHE1089-Main-N
Achain-PHE1121-Main-O
53.65%
Achain-ASP398-Main-N
Achain-VAL512-Main-O
53.65%
Cchain-PHE275-Main-N
Cchain-THR51-Main-O
53.53%
Cchain-LEU118-Main-N
Cchain-LYS129-Main-O
53.53%
Cchain-PHE106-Main-N
Cchain-LEU117-Main-O
53.29%
Cchain-CYS671-Main-N
Cchain-TYR695-Main-O
53.29%
Cchain-VAL1096-Main-N
Cchain-PHE1103-Main-O
53.05%
Cchain-ILE598-Main-N
Cchain-ALA609-Main-O
53.05%
Bchain-ARG509-Side-NH2
Bchain-ASP442-Side-OD1
53.05%
Achain-ALA1022-Main-N
Achain-ILE1018-Main-O
52.93%
Achain-ASN928-Main-N
Achain-ALA924-Main-O
52.81%
Cchain-VAL551-Main-N
Cchain-THR588-Main-O
52.81%
Cchain-ASP586-Main-N
Cchain-THR553-Main-O
52.81%
Achain-LEU223-Main-N
Achain-VAL36-Main-O
52.81%
Cchain-LEU277-Main-N
Cchain-HIS49-Main-O
52.57%
Cchain-VAL729-Main-N
Cchain-HIS1058-Main-O
52.46%
Cchain-SER640-Side-OG
Cchain-HIS625-Side-NE2
52.46%
Achain-MET697-Main-N
Achain-GLY669-Main-O
52.34%
Achain-PHE59-Main-N
Achain-PHE32-Main-O
52.34%
Bchain-PHE392-Main-N
Bchain-VAL524-Main-O
52.34%
Cchain-LEU117-Main-N
Cchain-PHE106-Main-O
52.34%
Cchain-LEU223-Main-N
Cchain-VAL36-Main-O
52.34%
Bchain-LEU241-Main-N
Bchain-GLY103-Main-O
52.22%
Cchain-LEU1063-Main-N
Cchain-PHE1052-Main-O
52.10%
Cchain-SER939-Side-OG
Cchain-GLN935-Main-O
52.10%
Achain-VAL1104-Main-N
Achain-GLN1113-Main-O
52.10%
(continued)
288
7 Spike (S) Glycoprotein
Fig. 7.7 Some strong SBs of the 6VXX-trimeric-spike-closed-model-1 confirmed by MD data in [321]
Supplementary Information
Fig. 7.7 (continued)
289
290 Table 7.1 (continued)
Table 7.2 The HBs with more than 50% occupancy rates during the 10 μs MD simulations for the 6VYB-trimeric-spikeopened-model-2
7 Spike (S) Glycoprotein Donor
Acceptor
Occupancy
Cchain-PHE1089-Main-N
Cchain-PHE1121-Main-O
51.98%
Achain-THR1120-Side-OG1
Achain-THR1116-Main-O
51.98%
Achain-GLN493-Main-N
Achain-TYR453-Main-O
51.98%
Cchain-THR881-Side-OG1
Cchain-LEU877-Main-O
51.74%
Achain-ILE598-Main-N
Achain-ALA609-Main-O
51.74%
Cchain-ASN919-Side-ND2
Cchain-VAL915-Main-O
51.74%
Cchain-VAL127-Main-N
Cchain-VAL120-Main-O
51.74%
Achain-CYS671-Main-N
Achain-TYR695-Main-O
51.50%
Cchain-THR1027-Side-OG1
Cchain-ASN1023-Main-O
51.38%
Cchain-PHE541-Main-N
Cchain-GLY548-Main-O
50.30%
Cchain-CYS1082-Main-N
Cchain-VAL1133-Main-O
50.30%
Bchain-VAL729-Main-N
Bchain-HIS1058-Main-O
50.30%
Bchain-TYR423-Main-N
Bchain-ILE418-Main-O
50.30%
Cchain-VAL511-Main-N
Cchain-ILE434-Main-O
50.30%
Bchain-VAL551-Main-N
Bchain-THR588-Main-O
50.30%
Bchain-PHE541-Main-N
Bchain-GLY548-Main-O
50.30%
Cchain-TYR451-Side-OH
Cchain-ASP442-Side-OD2
50.30%
Achain-THR1066-Main-N
Achain-SER721-Main-O
50.30%
Bchain-SER939-Side-OG
Bchain-GLN935-Main-O
50.30%
Cchain-TYR369-Side-OH
Achain-THR415-Side-OG1
50.30%
Achain-ILE651-Main-N
Achain-VAL610-Main-O
50.30%
Achain-LEU118-Main-N
Achain-LYS129-Main-O
50.30%
Achain-VAL362-Main-N
Achain-ASN334-Main-O
50.30%
Bchain-LEU118-Main-N
Bchain-LYS129-Main-O
50.30%
Achain-TYR695-Main-N
Achain-CYS671-Main-O
50.30%
Achain-PHE275-Main-N
Achain-THR51-Main-O
50.30%
Cchain-HIS1064-Side-ND1
Cchain-SER1051-Side-OG
50.30%
Achain-SER982-Side-OG
Achain-ASN978-Main-O
50.30%
Cchain-GLU132-Main-N
Cchain-ASN164-Main-O
50.30%
Bchain-HIS1088-Main-N
Bchain-ILE1081-Main-O
50.30%
Bchain-PHE59-Main-N
Bchain-PHE32-Main-O
50.30%
Bchain-TYR313-Side-OH
Bchain-GLU309-Main-O
50.30%
Bchain-ASP586-Main-N
Bchain-THR553-Main-O
50.30%
Achain-THR167-Side-OG1
Achain-GLN115-Side-OE1
50.30%
Donor
Acceptor
Occupancy
Achain-TYR37-Side-OH
Achain-LEU54-Main-O
72.10%
Bchain-TYR91-Main-N
Bchain-GLY268-Main-O
71.98%
Bchain-TYR37-Side-OH
Bchain-LEU54-Main-O
70.78%
Cchain-TYR37-Side-OH
Cchain-LEU54-Main-O
70.66%
Bchain-TYR269-Side-OH
Bchain-PRO85-Main-O
68.98%
Achain-ARG454-Main-N
Achain-ASN422-Side-OD1
68.38%
Cchain-TYR91-Main-N
Cchain-GLY268-Main-O
66.35%
Bchain-SER438-Side-OG
Bchain-ASP442-Side-OD2
64.31%
Bchain-LEU611-Main-N
Bchain-SER596-Main-O
64.07%
Achain-TYR313-Side-OH
Achain-GLU309-Main-O
64.07%
Achain-THR302-Side-OG1
Achain-GLU298-Main-O
63.59%
Bchain-TYR741-Side-OH
Bchain-LEU962-Main-O
63.11%
Cchain-ARG454-Main-N
Cchain-ASN422-Side-OD1
62.51%
Achain-TYR91-Main-N
Achain-GLY268-Main-O
62.28%
Cchain-THR299-Side-OG1
Cchain-PRO295-Main-O
62.04%
Achain-LEU118-Main-N
Achain-LYS129-Main-O
61.32%
Bchain-THR299-Side-OG1
Bchain-PRO295-Main-O
61.20%
Bchain-THR302-Side-OG1
Bchain-GLU298-Main-O
61.20%
Bchain-SER982-Side-OG
Bchain-ASN978-Main-O
60.72%
Bchain-VAL433-Main-N
Bchain-LYS378-Main-O
60.60%
Achain-ILE598-Main-N
Achain-ALA609-Main-O
60.00%
Cchain-THR302-Side-OG1
Cchain-GLU298-Main-O
59.76%
Cchain-LEU455-Main-N
Cchain-PRO491-Main-O
59.76%
Bchain-LEU455-Main-N
Bchain-PRO491-Main-O
59.52%
Bchain-TYR313-Side-OH
Bchain-GLU309-Main-O
59.28%
Achain-THR299-Side-OG1
Achain-PRO295-Main-O
59.16%
Bchain-LEU585-Main-N
Bchain-VAL576-Main-O
58.92%
(continued)
Supplementary Information Table 7.2 (continued)
291 Donor
Acceptor
Occupancy
Bchain-LEU513-Main-N
Bchain-CYS432-Main-O
58.92%
Achain-LEU611-Main-N
Achain-SER596-Main-O
58.80%
Achain-VAL433-Main-N
Achain-LYS378-Main-O
58.80%
Bchain-ARG509-Side-NE
Bchain-ASP442-Side-OD2
58.44%
Bchain-THR883-Side-OG1
Bchain-ALA879-Main-O
58.08%
Cchain-TYR269-Side-OH
Cchain-PRO85-Main-O
57.84%
Bchain-GLN1054-Side-NE2
Bchain-PRO1053-Main-O
57.84%
Achain-THR883-Side-OG1
Achain-ALA879-Main-O
57.49%
Cchain-VAL433-Main-N
Cchain-LYS378-Main-O
57.13%
Cchain-ILE598-Main-N
Cchain-ALA609-Main-O
57.13%
Bchain-ARG454-Main-N
Bchain-ASN422-Side-OD1
56.89%
Achain-GLN1054-Side-NE2
Achain-PRO1053-Main-O
56.77%
Achain-LEU585-Main-N
Achain-VAL576-Main-O
56.41%
Bchain-CYS671-Main-N
Bchain-TYR695-Main-O
56.41%
Bchain-LEU223-Main-N
Bchain-VAL36-Main-O
56.29%
Bchain-ILE598-Main-N
Bchain-ALA609-Main-O
56.17%
Cchain-LEU585-Main-N
Cchain-VAL576-Main-O
56.05%
Achain-VAL511-Main-N
Achain-ILE434-Main-O
56.05%
Achain-THR881-Side-OG1
Achain-LEU877-Main-O
55.93%
Cchain-LEU611-Main-N
Cchain-SER596-Main-O
55.81%
Achain-CYS1082-Main-N
Achain-VAL1133-Main-O
55.69%
Achain-PHE106-Main-N
Achain-LEU117-Main-O
55.69%
Bchain-ASP398-Main-N
Bchain-VAL512-Main-O
55.69%
Cchain-LEU650-Main-N
Cchain-PHE643-Main-O
55.69%
Achain-VAL539-Main-N
Achain-GLY550-Main-O
55.45%
Cchain-GLN1054-Side-NE2
Cchain-PRO1053-Main-O
55.45%
Cchain-SER1021-Side-OG
Cchain-GLU1017-Main-O
55.45%
Achain-THR1066-Side-OG1
Achain-LYS1045-Main-O
55.45%
Bchain-ILE651-Main-N
Bchain-VAL610-Main-O
55.33%
Bchain-GLN271-Main-N
Bchain-PHE55-Main-O
55.33%
Achain-ASP578-Main-N
Achain-GLU583-Main-O
55.33%
Cchain-THR883-Side-OG1
Cchain-ALA879-Main-O
55.09%
Achain-ASN777-Main-N
Achain-GLU773-Main-O
55.09%
Bchain-PHE106-Main-N
Bchain-LEU117-Main-O
55.09%
Cchain-LEU223-Main-N
Cchain-VAL36-Main-O
55.09%
Cchain-THR1066-Side-OG1
Cchain-LYS1045-Main-O
54.97%
Achain-CYS671-Main-N
Achain-TYR695-Main-O
54.85%
Cchain-VAL511-Main-N
Cchain-ILE434-Main-O
54.73%
Achain-SER1003-Side-OG
Achain-GLY999-Main-O
54.73%
Achain-SER939-Side-OG
Achain-GLN935-Main-O
54.61%
Cchain-PHE43-Main-N
Achain-PHE565-Main-O
54.37%
Bchain-HIS1088-Main-N
Bchain-ILE1081-Main-O
54.13%
Cchain-PHE106-Main-N
Cchain-LEU117-Main-O
54.13%
Bchain-PHE43-Main-N
Cchain-PHE565-Main-O
54.01%
Bchain-ASN919-Side-ND2
Bchain-VAL915-Main-O
54.01%
Achain-TYR741-Main-N
Achain-ASP737-Main-O
54.01%
Cchain-VAL539-Main-N
Cchain-GLY550-Main-O
53.89%
Bchain-SER1003-Side-OG
Bchain-GLY999-Main-O
53.77%
Cchain-LEU84-Main-N
Cchain-PHE238-Main-O
53.77%
Cchain-VAL551-Main-N
Cchain-THR588-Main-O
53.65%
Achain-THR1077-Side-OG1
Achain-PHE1095-Main-O
53.65%
Bchain-SER939-Side-OG
Bchain-GLN935-Main-O
53.53%
Achain-LEU513-Main-N
Achain-CYS432-Main-O
53.53%
Cchain-LEU560-Main-N
Cchain-GLN563-Side-OE1
53.41%
Bchain-TYR266-Main-N
Bchain-ALA93-Main-O
53.17%
Achain-ALA1022-Main-N
Achain-ILE1018-Main-O
53.05%
Cchain-ARG190-Main-N
Cchain-SER94-Main-O
53.05%
Cchain-THR881-Side-OG1
Cchain-LEU877-Main-O
52.93%
Cchain-ASP586-Main-N
Cchain-THR553-Main-O
52.93%
Cchain-HIS1064-Side-ND1
Cchain-SER1051-Side-OG
52.93%
Achain-PHE275-Main-N
Achain-THR51-Main-O
52.93%
Cchain-MET697-Main-N
Cchain-GLY669-Main-O
52.81%
Achain-GLN271-Main-N
Achain-PHE55-Main-O
52.81%
Cchain-ASN777-Main-N
Cchain-GLU773-Main-O
52.81%
Cchain-SER939-Side-OG
Cchain-GLN935-Main-O
52.69%
Cchain-ILE651-Main-N
Cchain-VAL610-Main-O
52.46%
Bchain-VAL539-Main-N
Bchain-GLY550-Main-O
52.46%
(continued)
292 Table 7.2 (continued)
Table 7.3 The HBs with more than 50% occupancy rates during the 10 μs MD simulations for the 1R4L-ACE2-closed-model-3
7 Spike (S) Glycoprotein Donor
Acceptor
Occupancy
Cchain-ASP442-Main-N
Cchain-SER438-Main-O
52.46%
Achain-LEU241-Main-N
Achain-GLY103-Main-O
52.34%
Cchain-TYR266-Main-N
Cchain-ALA93-Main-O
52.34%
Achain-ASN928-Main-N
Achain-ALA924-Main-O
52.34%
Cchain-CYS671-Main-N
Cchain-TYR695-Main-O
52.22%
Achain-THR1027-Side-OG1
Achain-ASN1023-Main-O
52.10%
Achain-HIS1064-Side-ND1
Achain-SER1051-Side-OG
52.10%
Cchain-THR531-Main-N
Cchain-VAL327-Main-O
51.86%
Achain-PHE1103-Main-N
Achain-VAL1096-Main-O
51.74%
Bchain-PHE59-Main-N
Bchain-PHE32-Main-O
51.74%
Achain-SER982-Side-OG
Achain-ASN978-Main-O
51.74%
Cchain-VAL512-Main-N
Cchain-ASP398-Main-O
51.74%
Achain-ASN919-Side-ND2
Achain-VAL915-Main-O
51.62%
Achain-PHE59-Main-N
Achain-PHE32-Main-O
51.62%
Bchain-ARG509-Side-NH2
Bchain-ASP442-Side-OD1
51.62%
Cchain-TYR695-Main-N
Cchain-CYS671-Main-O
51.62%
Bchain-PHE1089-Main-N
Bchain-PHE1121-Main-O
51.62%
Bchain-ARG158-Side-NH1
Bchain-GLU156-Side-OE2
51.62%
Cchain-VAL1096-Main-N
Cchain-PHE1103-Main-O
51.50%
Bchain-NLM1160-Side-ND2
Bchain-GLY339-Main-O
51.38%
Achain-PHE43-Main-N
Bchain-PHE565-Main-O
51.38%
Bchain-MET697-Main-N
Bchain-GLY669-Main-O
51.14%
Achain-ILE651-Main-N
Achain-VAL610-Main-O
51.02%
Cchain-PHE275-Main-N
Cchain-THR51-Main-O
51.02%
Bchain-TYR612-Main-N
Bchain-CYS649-Main-O
50.90%
Cchain-PHE59-Main-N
Cchain-PHE32-Main-O
50.90%
Bchain-ARG273-Main-N
Bchain-ASP53-Main-O
50.90%
Bchain-LEU118-Main-N
Bchain-LYS129-Main-O
50.90%
Achain-SER116-Main-N
Achain-CYS131-Main-O
50.90%
Achain-MET697-Main-N
Achain-GLY669-Main-O
50.78%
Bchain-VAL511-Main-N
Bchain-ILE434-Main-O
50.78%
Bchain-VAL551-Main-N
Bchain-THR588-Main-O
50.66%
Cchain-TYR741-Main-N
Cchain-ASP737-Main-O
50.66%
Bchain-SER803-Side-OG
Bchain-NLM1172-Side-OD1
50.54%
Bchain-TYR380-Main-N
Bchain-GLY431-Main-O
50.54%
Achain-LEU223-Main-N
Achain-VAL36-Main-O
50.54%
Achain-HIS245-Main-N
Achain-TYR248-Main-O
50.54%
Bchain-LEU650-Main-N
Bchain-PHE643-Main-O
50.42%
Bchain-LEU241-Main-N
Bchain-GLY103-Main-O
50.42%
Cchain-LEU118-Main-N
Cchain-LYS129-Main-O
50.42%
Bchain-THR1120-Side-OG1
Bchain-THR1116-Main-O
50.42%
Achain-LEU1063-Main-N
Achain-PHE1052-Main-O
50.42%
Cchain-TYR265-Main-N
Cchain-PHE65-Main-O
50.42%
Cchain-VAL729-Main-N
Cchain-HIS1058-Main-O
50.30%
Achain-TYR612-Main-N
Achain-CYS649-Main-O
50.30%
Achain-VAL512-Main-N
Achain-ASP398-Main-O
50.30%
Cchain-LEU277-Main-N
Cchain-HIS49-Main-O
50.18%
Bchain-PHE275-Main-N
Bchain-THR51-Main-O
50.18%
Bchain-GLU96-Main-N
Bchain-ASN188-Main-O
50.18%
Bchain-SER31-Main-N
Bchain-SER60-Main-O
50.06%
Bchain-TYR695-Side-OH
Bchain-GLU661-Main-O
50.06%
Donor
Acceptor
Occupancy
THR229-Side-OG1
ASP225-Main-O
66.27%
THR282-Side-OG1
LEU278-Main-O
62.86%
THR371-Side-OG1
ASP367-Main-O
61.87%
HID241-Main-N
TYR237-Main-O
61.37%
THR122-Side-OG1
THR118-Main-O
59.81%
TYR237-Side-OH
VAL485-Main-O
58.79%
LEU95-Main-N
LEU91-Main-O
53.68%
TYR516-Side-OH
THR229-Side-OG1
53.05%
SER77-Side-OG
LEU73-Main-O
51.01%
TYR252-Side-OH
LEU156-Main-O
50.64%
Supplementary Information Table 7.4 The HBs with more than 50% occupancy rates during the 10 μs MD simulations for the 1R42-ACE2-opened-model-4
Table 7.5 The HBs with more than 50% occupancy rates during the 10 μs MD simulations for the 6M17-spike-ACE2-bindingmodel-5
Table 7.6 Table S6. The HBs with more than 50% occupancy rates during the 10 μs MD simulations for the 6VW1-spike-ACE2-bindingmodel-6
293 Donor
Acceptor
Occupancy
TYR237-Side-OH
VAL485-Main-O
64.75%
THR229-Side-OG1
ASP225-Main-O
61.90%
THR371-Side-OG1
ASP367-Main-O
61.73%
TRP461-Main-N
GLU457-Main-O
61.25%
HID241-Main-N
TYR237-Main-O
58.96%
THR567-Side-OG1
TYR215-Main-O
58.78%
TYR516-Side-OH
THR229-Side-OG1
52.27%
HID373-Side-ND1
PHE369-Main-O
52.20%
THR129-Side-OG1
THR125-Main-O
51.70%
TYR521-Main-N
THR517-Main-O
51.27%
Donor
Acceptor
Occupancy
D:TYR237-Side-OH
D:VAL485-Main-O
69.54%
D:ARG357-Side-NH1
D:ASP355-Side-OD1
64.97%
F:ARG454-Main-N
F:ASN422-Side-OD1
63.83%
D:THR229-Side-OG1
D:ASP225-Main-O
63.29%
D:TRP461-Main-N
D:GLU457-Main-O
62.44%
D:HIS241-Main-N
D:TYR237-Main-O
61.56%
F:VAL433-Main-N
F:LYS378-Main-O
61.00%
D:THR567-Side-OG1
D:TYR215-Main-O
57.78%
D:SER331-Side-OG
D:PHE327-Main-O
57.30%
F:LEU513-Main-N
F:CYS432-Main-O
57.08%
D:TYR516-Side-OH
D:THR229-Side-OG1
56.66%
D:TYR521-Main-N
D:THR517-Main-O
56.56%
F:VAL511-Main-N
F:ILE434-Main-O
56.02%
D:THR27-Side-OG1
D:GLU23-Main-O
54.57%
D:THR129-Side-OG1
D:THR125-Main-O
54.03%
D:ASN49-Main-N
D:LEU45-Main-O
53.59%
F:THR500-Side-OG1
D:ASP355-Side-OD1
53.51%
D:TYR41-Side-OH
D:ASP355-Side-OD1
53.47%
D:THR371-Side-OG1
D:ASP367-Main-O
52.24%
D:GLU238-Main-N
D:LYS234-Main-O
50.57%
D:ASN194-Side-ND2
D:MET190-Main-O
50.03%
Donor
Acceptor
Occupancy
F:ARG454-Main-N
F:ASN422-Side-OD1
69.92%
B:TYR237-Side-OH
B:VAL485-Main-O
66.83%
B:SER317-Side-OG
B:PHE314-Main-O
66.21%
B:ARG357-Side-NH1
B:ASP355-Side-OD2
65.48%
B:TYR41-Side-OH
B:ASP355-Side-OD2
64.94%
B:THR229-Side-OG1
B:ASP225-Main-O
64.84%
B:HID241-Main-N
B:TYR237-Main-O
62.89%
B:TYR521-Main-N
B:THR517-Main-O
60.89%
B:THR282-Side-OG1
B:LEU278-Main-O
60.42%
B:THR567-Side-OG1
B:TYR215-Main-O
59.34%
F:LEU513-Main-N
F:CYX432-Main-O
58.81%
B:THR371-Side-OG1
B:ASP367-Main-O
57.92%
B:SER502-Side-OG
B:ASP499-Main-O
56.59%
F:VAL433-Main-N
F:LYS378-Main-O
55.27%
B:TYR516-Side-OH
B:THR229-Side-OG1
54.91%
F:ASP398-Main-N
F:VAL512-Main-O
54.78%
F:VAL511-Main-N
F:LEU434-Main-O
53.86%
B:LEU95-Main-N
B:LEU91-Main-O
53.43%
B:SER70-Side-OG
B:GLY66-Main-O
52.53%
B:THR414-Side-OG1
B:SER411-Main-O
52.24%
B:THR125-Side-OG1
B:ASN121-Main-O
51.69%
B:ASN33-Main-N
B:LEU29-Main-O
51.52%
B:THR27-Side-OG1
B:GLU23-Main-O
50.81%
F:THR438-Side-OG1
F:ASP442-Side-OD1
50.67%
B:VAL244-Main-N
B:LEU240-Main-O
50.56%
F:LEU461-Main-N
F:ASP420-Main-O
50.53%
B:TYR243-Side-OH
B:THR282-Main-O
50.08%
294
7 Spike (S) Glycoprotein
Table 7.7 The 50 drugs binding with SARS-CoV-2-trimericspike-RBDs of 2 μs MD trajectory data in [321] 01
Drug name
MD Data ID
ChEMBL
Spike-D, E, F
HBs
Alprostadil
10930523
1318789
F
lig.O-ASP364.O 45.83% lig.O-NMG343.O7 27.38% NMG343.O6-lig.O 7.14% NMG343.O3-lig.O 3.57% NMG343.O2-lig.O 1.19% SER371.OG-lig.O 19.64% ARG439.NH2-lig.O 4.76% ARG439.NH1-lig.O 4.17% ASP364.N-lig.O 3.57% PHE338.N-lig.O 3.57% GLY339.N-lig.O 1.19% THR372.OG1-lig.O 1.19%
02
Amcinonide
10940986
1200732
E
03
Aprepitant
10942625
1471
E: GLY482, GLU484
ASP364.N-lig.F 13.10%
F
lig.N-GLU484.OE2 11.31%
lig.O-ASP364.O 52.38% ASP364.N-lig.O 20.83%
lig.N-GLU484.OE1 6.55% GLU484.N-lig.O 5.95% VAL483.N-lig.O 2.98% lig.N-SER366.OG 0.60% lig.N-ASN481.O 0.60% lig.N-ASN481.OD1 0.60% VAL483.N-lig.N 0.60% GLY485.N-lig.O 0.60% 04
Atazanavir
10921672
1163
D
lig.O-ASP364.OD1 46.43%
F
lig.N-ASP364.OD1 42.86% lig.O-ASP364.OD2 23.81% lig.N-ASP364.OD2 17.26% TYR489.OH-lig.O 14.88% ASN370.ND2-lig.O 7.14% NMG343.O4-lig.O 2.98% lig.N-SER371.OG 2.38% lig.N-TYR489.OH 1.79% lig.N-ASN370.OD1 1.19% lig.N-ASN331.OD1 0.60% ASN331.N-lig.O 0.60% GLN493.NE2-lig.N 0.60% SER371.OG-lig.O 0.60% lig.N-NMG343.O2 0.60% NMG343.O2-lig.O 0.60%
05
Atorvastatin
10930821
1487
E
lig.O-ASN487.O 22.02%
F
ASN487.ND2-lig.O 14.29% ALA475.N-lig.O 13.69% lig.O-lig.O 13.10% lig.O-ASN487.OD1 8.33% lig.O-GLN474.OE1 3.57% lig.N-lig.C 2.38% SER477.N-lig.F 1.79% ASN487.N-lig.O 1.79% NMG343.O3/4-lig.O 1.19% lig.O-ASP389.OD1 0.60% ASN331.ND2-lig.O 0.60% lig.O-ASP389.OD2 0.60% THR333.OG1-lig.O 0.60% ASN388.ND2-lig.C 0.60% lig.O-PRO527.O 0.60%
06
Atropine
10942532
1396281
E
lig.N-ASP420.OD1 45.83%
F
lig.O-SER477.OG 32.74% lig.N-ASP420.OD2 22.02% ASN370.ND2-lig.O 1.19% THR385.OG1-lig.O 0.60%
(continued)
Supplementary Information
295
Table 7.7 (continued) 07
Drug name
MD Data ID
ChEMBL
Spike-D, E, F
AZD-8330
10941318
3182621
D
ARG439.NH2-lig.O 27.98%
E
GLN506.NE2-lig.O 13.10%
F
HBs
lig.O-PRO499.O 7.74% ARG439.NE-lig.O 5.36% GLN506.NE2-lig.F 4.17% ARG439.NH1-lig.O 3.57% lig.O-ARG439.O 1.19% lig.O-ASN440.OD1 1.19% lig.O-lig.N 1.19% lig.N-THR500.O 1.19% TYR508.OH-lig.O 1.19% ARG439.NE-lig.N/C 0.60% NMG343.O6-lig.O 0.60% ASN440.ND2-lig.O 0.60%
08
Azilsartan
10941382
57242
D
ARG439.NH2-lig.O 40.48%
E
GLN506.NE2-lig.N 15.48%
F
ARG439.NH2-lig.N 11.31% ARG439.NH1-lig.O 11.31% ARG439.NE-lig.O 10.12% ASN440.ND2-lig.O 5.95% GLN506.NE2-lig.O 4.76% ASN501.ND2-lig.N 4.17% GLY502.N-lig.O 4.17% ASN437.ND2-lig.O 2.98% ARG439.NH1-lig.N 1.79% ASN440.ND2-lig.N 1.79% VAL503.N-lig.O 1.19% THR500.OG1-lig.O 1.19% VAL503.N-lig.N 0.60% ASN437.ND2-lig.N 0.60%
09
Brigatinib
10930748
3545311
D
lig.N-ASP389.OD2 17.86%
E
lig.N-ASP389.OD1 13.69% ASN370.ND2-lig.N 3.57% lig.N-TYR453.OH 2.98% SER477.OG-lig.N 2.98% TYR453.OH-lig.O 2.98% lig.N-GLY476.O 1.79% lig.N-PRO527.O 1.19% GLN493.NE2-lig.N 1.19% ASN370.ND2-lig.O 0.60% TYR421.OH-lig.N 0.60% GLN493.NE2-lig.O 0.60% lig.N-ASN388.O 0.60% lig.N-SER477.OG 0.60% THR372.OG1-lig.O 0.60% lig.N-lig.O 0.60%
10
Calcifediol
10941841
1040
E
lig.O-PRO337.O 41.07%
F
lig.O-GLU484.OE1 8.93% NMG343.N2-lig.O 7.74% lig.O-GLU484.OE2 6.55% lig.O-ASP364.O 1.79% lig.O-ASN437.O 1.79% lig.O-VAL483.O 1.19% lig.O-NMG343.O7/4 0.60% lig.O-TYR365.OH 0.60% lig.O-GLU484.O 0.60%
11
Captopril
10940762
27686
D
ARG408.NH2-lig.O 27.38%
E: LYS378
ARG408.NH1-lig.O 15.48%
F
LYS378.NZ-lig.O 12.50% ARG439.NH1-lig.O 5.36% ARG439.NH2-lig.O 3.57% VAL503.N-lig.O 2.98% ARG408.NE-lig.O 1.79%
(continued)
296
7 Spike (S) Glycoprotein
Table 7.7 (continued) 12
Drug name
MD Data ID
ChEMBL
Spike-D, E, F
Cefamandole nafate
10941424
1484057
D
HBs GLN506.NE2-lig.O 48.21%
E
VAL503.N-lig.O 19.05%
F
ARG439.NH2-lig.O 13.69% ARG439.NH1-lig.O 10.71% ASN437.N-lig.N 1.19% ARG439.NE-lig.O 1.19%
13
Cefixime
10918686
1317573
D
GLN506.NE2-lig.O 57.14%
E
ARG439.NH2-lig.O 48.81%
F
ARG439.NE-lig.O 31.55% VAL503.N-lig.O 16.67% lig.N-ASN440.OD1 5.36% ARG439.NE-lig.N 0.60%
14
Clobazam
10941112
70418
D
CYX488.N-lig.O 19.64%
F
ASN487.N-lig.O 11.31% VAL483.N-lig.O 7.14% GLY485.N-lig.O 2.38% GLU484.N-lig.O 1.79% ASN487.ND2-lig.O 0.60%
15
Cobimetinib
10941772
2146883
E
lig.N-GLU340.OE1 16.07% lig.N-GLU340.OE2 14.88% lig.O-GLU340.OE1 14.29% lig.O-GLU340.OE2 13.10% lig.O-PRO337.O 13.10% lig.N-LEU335.O 0.60% LYS356.NZ-lig.O 0.60% lig.O-GLU340.O 0.60%
16
CP-195543
10941273
301829
D
ARG439.NH2-lig.O 23.81%
E
ARG439.NE-lig.O 22.02%
F
ASN440.ND2-lig.O 10.12% ARG439.NH1-lig.O 1.79% GLN506.NE2-lig.O 1.19%
17
Darunavir
10918731
1201127
D
lig.O-lig.O 58.93%
F
lig.N-SER375.OG 26.79% SER375.OG-lig.O 19.05% lig.N-SER371.O 11.31% TYR508.OH-lig.N 10.12% GLY502.N-lig.O 8.93% lig.N-THR376.OG1 5.95% ARG439.NH1-lig.O 3.57% GLY496.N-lig.O 2.38% ARG439.NH2-lig.O 1.79% lig.N-PHE373.O 1.79% lig.N-ASP405.OD1 1.19% NMG343.N2-lig.O 1.19% GLN506.NE2-lig.O 0.60% NMG343.O3-lig.O 0.60% GLN493.NE2-lig.O 0.60% ASN437.ND2-lig.O 0.60% lig.N-GLY504.O 0.60% GLN498.NE2-lig.O 0.60% TYR508.OH-lig.C 0.60% lig.O-GLY496.O 0.60% LYS403.NZ-lig.O 0.60% lig.N-SER494.O 0.60% lig.O-PHE373.O 0.60%
18
Deferasirox
10941722
550348
E
lig.O-lig.N 8.33% LYS356.NZ-lig.O 6.55% ASP364.N-lig.O 5.95% ASN360.ND2-lig.O 2.98% lig.O-GLU340.OE2 1.79%
(continued)
Supplementary Information
297
Table 7.7 (continued) 19
Drug name
MD Data ID
ChEMBL
Spike-D, E, F
HBs
Dihydroergotamine
10942525
3561903
D
lig.N-SER366.OG 19.05%
F
lig.O-ASP364.OD1 4.17% lig.N-ASP364.OD2 3.57% lig.N-ASP364.OD1 2.98% lig.O-ASP364.OD2 2.38% ASN370.ND2-lig.O 1.19% lig.N-ASP389.OD2 1.19% NMG343.O6-lig.O 0.60% lig.N-ASN388.OD1 0.60% lig.O-lig.C 0.60% ASN481.ND2-lig.O 0.60% TYR489.OH-lig.O 0.60% lig.O-SER366.OG 0.60%
20
Divalproex sodium
10931330
109
E
lig.O-PRO337.O 43.45% ASP364.N-lig.O 12.50% TYR365.N-lig.O 9.52% lig.O-ASP364.OD1 9.52% lig.O-ASP364.OD2 4.17% lig.O-ASP364.O 1.19%
21
Duloxetine
10918694
424660
D
lig.N-ASP389.OD1 18.45%
E
lig.N-ASP389.OD2 14.88% lig.N-ASP364.OD1 0.60% lig.N-ASP389.CG 0.60%
22 23
Efavirenz Fluticasone propionate
10931344 10930719
59507 1473
D
lig.N-GLY476.O 44.64%
E
lig.N-ASN388.OD1 0.60%
E: THR415
THR415.OG1-lig.O 10.12%
F
lig.O-THR415.O 2.38% lig.O-THR415.OG1 1.19%
24
Iloprost
10906572
494
D: PHE486
lig.O-PRO337.O 49.40%
E
LYS356.NZ-lig.O 32.14% lig.O-CYX336.O 22.62% lig.O-GLU340.OE1 6.55% lig.O-GLU340.OE2 4.76% lig.O-lig.C 1.19% THR345.OG1-lig.O 1.19% SER399.OG-lig.O 0.60% GLU340.N-lig.O 0.60%
25
Isocarboxazid
10941783
1201168
26
Ketoconazole
10941101
157101
D
ASP364.N-lig.O 7.74%
F
lig.N-ASP364.O 4.17%
D
ASP364.N-lig.O 9.52%
F: PHE486
ASN487.ND2-lig.O 3.57% NMG343.O6-lig.N 1.19% TYR489.OH-lig.C 0.60% TYR489.OH-lig.O 0.60%
27
Lapatinib
10942558
1076241
D
lig.N-ASP364.OD1 14.29%
F
lig.N-ASP364.OD2 13.69% lig.N-CYX336.O 5.95% NMG343.N2-lig.O 2.38% lig.N-NMG343.O7 1.79% NMG343.O2-lig.N 1.79% lig.N-GLN474.O 1.19% GLN474.NE2-lig.O 1.19% NMG343.O3-lig.O 0.60% ASN487.N-lig.O 0.60% ASN487.ND2-lig.O 0.60% NMG343.O6-lig.O 0.60% lig.N-ILE332.O 0.60% lig.N-LEU335.O 0.60% THR333.OG1-lig.O 0.60%
(continued)
298
7 Spike (S) Glycoprotein
Table 7.7 (continued) 28
Drug name
MD Data ID
ChEMBL
Spike-D, E, F
Levomefolate calcium
10941419
1221561
D
ARG439.NH2-lig.O 53.57%
E
ARG439.NH1-lig.O 29.17%
F
HBs
TYR508.OH-lig.O 25.60% GLN506.NE2-lig.O 22.02% ARG439.NE-lig.O 16.67% lig.N-ASN501.O 5.36% GLN506.NE2-lig.N 2.38% lig.N-ALA435.O 2.38% ASN440.ND2-lig.O 1.79% lig.N-lig.O 0.60% lig.N-SER375.OG 0.60% lig.N-PRO499.O 0.60% VAL503.N-lig.O 0.60% lig.N-THR500.O 0.60%
29
Lometrexol
10941234
170101
D
ARG439.NH2-lig.O 51.19%
E
ARG439.NE-lig.O 32.14%
F
ARG439.NH1-lig.O 31.55% ASN440.ND2-lig.O 16.67% GLN506.NE2-lig.O 5.36% TYR508.OH-lig.N 2.98% ASN437.N-lig.O 1.79% lig.N-lig.O 1.19% THR500.OG1-lig.O 0.60% NMG343.N2-lig.N 0.60% SER375.OG-lig.N 0.60% NMG343.O6-lig.O 0.60% ARG439.NH1-lig.C 0.60% lig.N-PHE373.O 0.60% GLY504.N-lig.N 0.60%
30
Lomibuvir
10931493
3182952
D E
lig.O-lig.N 10.71% PHE374.N-lig.O 3.57% TRP436.NE1-lig.O 2.98% lig.O-PHE342.O 2.38% ASN440.ND2-lig.O 1.79% NMG343.O6-lig.O 1.19% GLN493.NE2-lig.O 1.19% lig.O-ASN437.O 0.60%
31
Megestrol acetate
10932268
1201139
D
lig.O-NMG343.OD1 69.05%
E
THR372.OG1-lig.O 29.17% lig.N-PHE342.O 19.05% THR372.N-lig.O 6.55% TRP436.NE1-lig.C 1.19% ARG509.NH1-lig.N 0.60% GLN493.NE2-lig.O 0.60%
32
Methsuximide
10906575
697
D
THR376.OG1-lig.O 5.95%
F: SER477
ARG408.NH1-lig.O 2.38% ARG408.NE-lig.O 1.19% ARG408.NH2-lig.O 0.60% LYS378.NZ-lig.O 0.60%
33
Naloxone
10906602
609673
D
lig.O-ASP405.OD1 62.50%
E
lig.N-ASP405.OD2 47.02% ALA384.N-lig.O 35.71% lig.O-ASP405.OD2 11.31% lig.O-VAL382.O 6.55% ARG408.NH2-lig.O 6.55% lig.N-ASP405.OD1 5.36%
34
Nebivolol
10918707
1201731
D
lig.O-ASP420.OD2 42.86%
E
lig.O-ASP420.OD1 17.26% ASN460.ND2-lig.O 4.17% lig.N-ASP420.OD2 4.17%
A
lig.O-A:ASP985.OD2 1.19%
A
lig.O-A:ASP985.OD1 1.19% lig.N-ASP420.OD1 1.19% lig.N-ASN460.OD1 0.60% lig.N-THR415.OG1 0.60% lig.O-TYR421.OH 0.60% lig.O-THR385.OG1 0.60%
(continued)
Supplementary Information
299
Table 7.7 (continued) 35
Drug name
MD Data ID
ChEMBL
Spike-D, E, F
HBs
Nilutamide
10942574
1274
F
ASP364.N-lig.O 10.71% VAL367.N-lig.O 1.79% lig.N-ASP364.OD1 1.19% lig.N-ASP364.OD2 0.60% lig.N-NMG343.OD1 0.60% PHE342.N-lig.O 0.60% lig.N-NMG343.O7 0.60% NMG343.N2-lig.O 0.60% lig.N-NMG343.O4 0.60%
36 37
Nitazoxanide Pelitrexol
10930676 10941210
1401 2107361
D
ARG509.NH1-lig.O 17.26%
F: VAL503, TYR505
lig.N-PHE342.O 0.60%
D
TYR508.OH-lig.O 42.86%
E
ARG439.NH2-lig.O 35.12%
F
ARG439.NH1-lig.O 33.93% NMG343.O4-lig.O 13.69% NMG343.O3-lig.O 11.31% GLN506.NE2-lig.O 5.36% ARG439.NE-lig.O 4.76% TYR508.OH-lig.N 3.57% lig.N-THR500.O 2.98% ASN440.ND2-lig.O 1.79% VAL503.N-lig.O 1.79% THR500.OG1-lig.O 1.19% lig.N-THR376.OG1 1.19% ASN437.ND2-lig.N 1.19% VAL503.N-lig.N 0.60% SER375.OG-lig.N 0.60% lig.N-lig.O 0.60% NMG343.O3-lig.N 0.60% GLN498.NE2-lig.O 0.60% TYR508.OH-lig.C 0.60% lig.N-ALA435.O 0.60%
38
Raltitrexed
10941177
140144
D
ARG439.NH2-lig.O 60.12%
E
ARG439.NH1-lig.O 34.52%
F
ARG439.NE-lig.O 22.02% NMG343.O4-lig.O 12.50% NMG343.O3-lig.O 10.71% NMG343.O6-lig.O 8.93% GLN506.NE2-lig.O 8.33% ASN437.N-lig.O 6.55% ASN440.ND2-lig.O 6.55% lig.N-PHE373.O 5.36% NMG343.O2-lig.O 4.76% ASN437.N-lig.N 1.79% TYR508.OH-lig.C 1.19% ASN440.N-lig.O 0.60% lig.N-ASN440.OD1 0.60% TYR508.OH-lig.O 0.60% GLY504.N-lig.O 0.60% TYR508.OH-lig.N 0.60% lig.N-TYR505.OH 0.60%
39
Rebamipide
10941364
1697771
D
GLN506.NE2-lig.O 45.24%
E
ARG439.NH2-lig.O 34.52%
F
ARG439.NH1-lig.O 23.81% GLN506.NE2-lig.C 4.76% lig.N-ASN501.O 3.57% ARG439.NE-lig.O 2.38% GLN506.NE2-lig.N 1.19%
40
Recoflavone
10941282
4297606
D
ARG439.NH2-lig.O 20.24%
E
ARG439.NH1-lig.O 13.69%
F
ASN437.N-lig.O 9.52% ARG439.NE-lig.O 7.74% GLN506.NE2-lig.O 5.36% THR500.OG1-lig.O 4.17% TYR508.OH-lig.C 1.79% TYR508.OH-lig.O 0.60% SER375.OG-lig.O 0.60%
(continued)
300
7 Spike (S) Glycoprotein
Table 7.7 (continued) 41
Drug name
MD Data ID
ChEMBL
Spike-D, E, F
Ritonavir
10921687
159496
D
HBs lig.O-NMG343.OD1 69.05%
F
THR372.OG1-lig.O 29.17% lig.N-PHE342.O 19.05% THR372.N-lig.O 6.55% TRP436.NE1-lig.C 1.19% ARG509.NH1-lig.N 0.60% GLN493.NE2-lig.O 0.60%
42
Rivaroxaban
10940767
3183768
D
THR376.OG1-lig.O 5.95%
E: SER371
ARG408.NH1-lig.O 2.38% ARG408.NE-lig.O 1.19% ARG408.NH2-lig.O 0.60% LYS378.NZ-lig.O 0.60%
43
Tadalafil
10942509
1671905
D
lig.N-LEU455.O 28.57%
E
TYR365.N-lig.O 3.57% TYR369.OH-lig.C 1.79% PHE490.N-lig.O 1.79%
44
Telaprevir
10931335
231813
D F
lig.N-ALA475.O 26.19% SER477.OG-lig.O 4.76% lig.N-SER366.OG 2.98% THR372.OG1-lig.O 2.98% ASN370.ND2-lig.O 2.38% lig.N-lig.O 1.79% NMG343.N2-lig.O 0.60%
45
Tenofovir
10931329
315593
D E
lig.O-ASP406.OD1 38.10% LYS403.NZ-lig.O 21.43% lig.O-ASP405.OD2 16.67% lig.O-ASP405.OD1 13.69% ASN370.ND2-lig.N 8.93% lig.O-ASP406.OD2 7.74% lig.O-ASP389.OD1 6.55% lig.O-ASP389.OD2 5.36% lig.N-ASN370.OD1 5.36% ASN481.ND2-lig.N 2.98% lig.O-ASP420.OD1 2.38% lig.N-TYR453.OH 1.19% TYR453.OH-lig.N 1.19% GLN409.NE2-lig.O 1.19% GLN493.NE2-lig.N 1.19% lig.N-GLN409.NE2 0.60% lig.N-ASP406.OD2 0.60% ASN388.ND2-lig.O 0.60% lig.N-ALA384.O 0.60% lig.O-THR385.OG1 0.60% ASN388.ND2-lig.N 0.60% lig.N-ASN370.ND2 0.60% lig.N-ASP389.OD1 0.60% lig.N-THR385.O 0.60% lig.N-GLN493.OE1 0.60%
46
Terazosin
10918688
1201091
D
lig.N-VAL483.O 29.76%
F
lig.N-GLY485.O 24.40% THR372.OG1-lig.O 8.33% lig.N-GLU484.OE1 1.79% lig.N-GLU484.OE2 1.19% THR372.OG1-lig.C 0.60% lig.N-ASN370.OD1 0.60% TYR489.OH-lig.N 0.60% SER494.OG-lig.O 0.60% lig.N-SER371.OG 0.60%
47
Treprostinil
10906555
3561314
E
NMG343.ND2-lig.O 42.26% lig.O-ASP364.O 22.02% NMG343.N2-lig.O 8.93% NMG343.O6-lig.O 1.19% ASP364.N-lig.O 0.60% lig.O-ASP364.OD1 0.60% ASN487.ND2-lig.O 0.60%
(continued)
Supplementary Information
301
Table 7.7 (continued) 48 49
Drug name
MD Data ID
ChEMBL
Spike-D, E, F
HBs
Triazolam
10941754
646
D
GLN493.NE2-lig.C 1.19%
E
TYR365.N-lig.N 0.60%
D
GLN506.NE2-lig.N 16.67%
Vorapaxar
10930743
2107386
E F
lig.N-PRO499.O 14.29% GLN506.NE2-lig.O 10.12% lig.N-THR500.O 3.57% VAL503.N-lig.O 1.79% ARG439.NE-lig.O 1.79% ARG439.NH2-lig.O 1.19% ARG439.NH1-lig.O 1.19% ASN440.ND2-lig.O 1.19%
50
Zileuton
10930851
93
D: ASP405, ARG408 E
lig.O-ASP405.OD1 30.95% lig.O-ASP405.OD2 4.17% lig.N-ASP405.O 2.98% ARG408.NE-lig.O 1.79% ARG408.NH1-lig.O 1.79% lig.N-ASP405.OD2 0.60% lig.N-ASP405.OD1 0.60% lig.N-GLY404.O 0.60%
302
Fig. 7.7 (continued)
7 Spike (S) Glycoprotein
Supplementary Information
303
Fig. 7.8 Some strong SBs of the 6VYB-trimeric-spike-opened-model-2 confirmed by MD data in [321]
304
Fig. 7.8 (continued)
7 Spike (S) Glycoprotein
Supplementary Information
305
Fig. 7.9 Some strong SBs of the 1R4L-ACE2-closed-model-3 confirmed by MD data in [321]
306
7 Spike (S) Glycoprotein
Fig. 7.10 Some strong SBs of the 1R42-ACE2-opened-model-4 confirmed by MD data in [321]
Supplementary Information
307
Fig. 7.11 Some SBs of the 6M17-spike-ACE2-binding-model-5 confirmed by MD data in [321]
308
Fig. 7.12 Some data in [321]
7 Spike (S) Glycoprotein
Supplementary Information
Fig. 7.12 (continued)
309
310
7 Spike (S) Glycoprotein
Fig. 7.13 Some strong and important HBs (with average values of 2.860864, 2.848252, 2.919316, and 3.650197 Å, respectively) of the 6VXX-trimeric-spike-closed-model-1 confirmed by MD data in [321]
Fig. 7.14 Some strong and important HBs (with average values of 2.826612, 2.827929, 2.937867, 2.933415, and 2.911408 Å, respectively) of the 6VYB-trimeric-spike-opened-model-2 confirmed by MD data in [321]
Supplementary Information
311
Fig. 7.15 Some strong and important HBs (with average values of 2.907522 (broken during frames 103–169 and 211–235), 3.143333 (broken during frames 1–32, 103–202, 272–279, and 380–404), and 2.921907 Å, respectively) of the 1R4L-ACE2-closed-model-3 confirmed by MD data in [321]
Fig. 7.16 Some strong and important HBs (with average values of 2.827859, 2824532, and 2.940768 Å, respectively) of the 1R42-ACE2-opened-model-4 confirmed by MD data in [321]
312
7 Spike (S) Glycoprotein
Fig. 7.17 Some strong and important HBs (with average values of 2.849615, 2.903840, 2.904051, 2.827907, 2.803045, 2.881762, 3.173316, and 2.803158 Å, respectively) of the 6M17-spikeACE2-binding-model-5 confirmed by MD data in [321]
Supplementary Information
313
Fig. 7.18 Some strong and important HBs (with average values of 2.868132, 2.865653, 2.921195, 2.814954, 2.920962, 2.900633, 2.913999, 2.912548, 2.71528, and 2.791970 Å, respectively) of the 6VW1-spike-ACE2-binding-model-6 confirmed by MD data in [321]
314
Fig. 7.18 continued
7 Spike (S) Glycoprotein
Supplementary Information
315
Fig. 7.19 The 115 ligand interaction diagrams of the optimized 5_Swiss_5_SS-6VSB model of [127]
316
Fig. 7.19 continued
7 Spike (S) Glycoprotein
Supplementary Information
Fig. 7.19 continued
317
318
Fig. 7.19 continued
7 Spike (S) Glycoprotein
Table 7.8 The 115 glycan shields and their binding residues of SARS-CoV-2-spike in the optimized 5_Swiss_5_SS-6VSB model of [127] The glycan shield
Spike residues binding with the glycan shield
Ligand-3361-4YB
TYR2, NLN35, THR37, PHE39, LEU58, PRO59, TYR243
Ligand-3366-OMA
ARG211
Ligand-3368-UYB
GLY46, NLN48, THR50, GLN108, PHE109, CYS110, ASN111
Ligand-3373-OYB
ASP112, ARG132
Ligand-3374-2MA
LYS51, PHE53, ASN111, ASP112, PHE114, GLY116, VAL117, TYR118, ARG132
Ligand-3376-OfA
GLY46, THR50, LYS51, ARG52, PHE53, PHE109, ASN111
Ligand-3377-4YB
NLN96, THR98, ASN99, MET127, PHE131, VAL145
Ligand-3384-UYB
GLN108, VAL117, LYS121, NLN123, SER135, ASN138
Ligand-3389-2MA
SER86, GLN108, PHE109, CYS110
Ligand-3391-OfA
LYS103, NLN123, GLU128, SER129, TYR134, SER135
Ligand-3392-UYB
ASN138, NLN139, TYR2565, ILE2682, SER2683, THR2684, GLU2685, ILE2686, PHE2704
Ligand-3399-OfA
LYS87, THR88, GLN89, GLU106, ARG2680, ASP2681, ILE2682, SER2683
Ligand-3406-2MA
GLN26, ASP27, LEU28, ASP62, ILE171, PRO246, PRO605, VMB3402, VMA3403
Ligand-3408-2MA
GLU298, SER299, ASN514, THR1841, VMB3402, OMA3405
Ligand-3410-UYB
PRO148, PHE149, LEU150, MET151, LEU153, GLU154, NLN256, LEU2774, PRO2775
Ligand-3418-OfA
TYR12, LEU150, MET151, ASP152, LYS180, HIS181, GLU198, THR258, LEU2774
Ligand-3419-UYB
NLN305, ILE306, THR307, ASN1219, VAL1265, GLN1267
Ligand-3424-2MA
VAL1221, LYS1223, GLU1250, TYR1254, GLU1263, VAL1265
Ligand-3426-OfA
NLN305, ILE306, THR307, LEU309, VAL336, PRO501
Ligand-3427-UYB
NLN317
Ligand-3434-OfA
GLU314, NLN317, ALA318, THR319
Ligand-3435-4YB
THR281, GLU283, NLN577, LYS809, GLN810, TYR811, SER913, SER914
Ligand-3440-OMA
LEU795, ASN798, LYS799, LEU802, GLN810, TYR811, GLY812, SER913
Ligand-3441-OMA
GLN810, TYR811, GLY812, ASP813
Ligand-3442-UYB
NLN590, THR592, GLN618
Ligand-3449-OfA
NLN590, THR592, GLU593
Ligand-3450-4YB
NLN590, GLN618, HIS629, NLN631
Ligand-3455-OMA
ASP588, ARG620
Ligand-3456-2MA
ARG620, PRO1906, SER1907, ARG1909, ASP1961, GLU1962
Ligand-3458-4YB
NLN683, ASN684, ASP1890
Ligand-3464-OMA
ILE1104
Ligand-3465-4YB
THR690, NLN691, LEU896, GLN1045, ASN3339, VAL3342
Ligand-3470-OMA
PRO1086
Ligand-3472-4YB
LYS769, NLN775, SER777, GLN778, PHE791, GLN810, ILE905, GLY906, GLN909, ASP910, SER913, SER914
Ligand-3479-4YB
ALA680, SER682, ASN684, SER685, NLN1048, PHE1049, THR1050, PRO1997, ILE1888, LYS1889, GLN1989
Ligand-3486-4YB
NLN1072, GLY1073, THR1074, HIS1075, PHE1077
Ligand-3491-2MA
THR1110, TYR1112
Ligand-3493-UYB
NLN1108, ASN1109, HIS1075
Ligand-3501-4YB
LEU1150, PRO1151, SER1154, NLN1155, VAL1156, ASN1181, GLY1362, TYR1363, LEU1364, GLN1365, PRO1416, THR1417, GLU1418, SER1419, ASN1634, VMB3542, VMA3543, 2MA3544, OMA3545
Ligand-3506-OMA
GLN1365, 0MA3545
Ligand-3507-OMA
PRO1179, PHE1180, ASN1181, ASP1182, NLN1328, ILE1329, THR1330, ARG1331, 4YB3540, 2MA3544
Ligand-3508-UYB
VAL1164, GLY1166, THR1167, NLN1168, ARG1172, GLN1228, ASN1231, ASP1232
Ligand-3516-OfA
NLN1168, ARG1172, PHE1173, ASP1174, PHE1229, ASN1231
Ligand-3517-4YB
ARG1196, NLN1216, VAL1221, TYR1238, GLU1248, SER1249, GLU1250, PHE1251, TYR1254
Ligand-3524-UYB
HIS1240, ASN1242, NLN1243
Ligand-3531-OfA
ALA1217, THR1218
Ligand-3532-UYB
PRO437, ARG440, CYS454, ASN455, ASN1258, NLN1259
Ligand-3537-2MA
PRO437, GLU439, ARG440, ASP441, ILE442
Ligand-3539-OfA
LYS1207, THR1208, GLN1209, GLU1226
Ligand-3546-2MA
GLN1146, THR2961, GLU2962, SER2964, ASN2965, LEU2968, LYS3200, 4YB3540, 4YB3541, VMA3542, VMA3543
Ligand-3548-2MA
SER1419, LYS1480, ASP1483, THR1641, LEU3195, SER3196, 4YB3541, VMB3542
Ligand-3550-UYB
ASN530, LYS531, GLU1375, NLN1376, ALA1940, ASP1942
Ligand-3556-2MA
ASN1918, ALA1923, ASP1924, ASP1942
Ligand-3558-OfA
ASN1374, GLU1375
Ligand-3559-UYB
PRO1424, NLN1425, ILE1426,PRO1673, GLN1674
Ligand-3564-2MA
ASN1454, THR2338, ASN2339
Ligand-3566-OfA
NLN1425, ILE1426, THR1427, ASN1428
Ligand-3567-UYB
SER433, ASN434, LEU435, PHE1436, NLN1437, ALA1466, SER1467, PHE1468, SER1469, TRP1530, ASN1531, SER1532,ASN1533, ASN1534, LEU1535, VAL1597, GLN1600
Ligand-3572-2MA
SER433, ASN434, LEU435, LYS436, PRO437, PHE438, ALA1466
Ligand-3574-OfA
NLN1437, ALA1438, THR1439, LEU1535
Ligand-3575-4YB
THR1401, ARG1776, LYS1919, LYS1929, TYR1931, ASP1933, CYS1934, LEU1935, ASP1937, SER2033, SER2034, THR2035, ALA2036, SER2037
Ligand-3581-OMA
GLY1936, ASP1937, ILE1938
Ligand-3582-UYB
NLN1710, CYS1711, THR1712
Ligand-3589-OfA
CYS1711, THR1712, VAL1736
Ligand-3590-4YB
NLN1751, SER1753, CYS3054, LEU3055, GLY3056
Ligand-3596-2MA
SER3024, LYS3025, PHE3047, GLN3050, TYR30511, GLY3052, CYS3054, LEU3055
Ligand-3598-4YB
NLN1803, ASN1804, THR2171, ALA2172, PRO2173, GLY2225, ILE2226, VAL2227
(continued)
320
7 Spike (S) Glycoprotein
Table 7.8 (continued) The glycan shield
Spike residues binding with the glycan shield
Ligand-3604-OMA
CYS2220, ASP2221, ILE2226, NLN2228
Ligand-3605-4YB
THR1810, NLN1811, TYR2204, PRO2206, PRO2237, LEU2239, ASP2240
Ligand-3610-OMA
GLU2205, PRO2206, GLN2207, ILE2208, PHE2197, PRO2237
Ligand-3611-OMA
ASN1099, ASP1101, VAL1102
Ligand-3612-4YB
SER1897, GLN1898, PHE1911, GLY2026, GLN2029, ASP2030, SER2033
Ligand-3619-4YB
ALA1800, TYR1801, SER1802, SER1805, SER1802, NLN2168, THR2170, NLN2192, GLN3109
Ligand-3626-4YB
THR1810, NLN1811, GLN2165, GLU2166, LYS2167, PHE2169, NLN2192, PHE2197, TYR2204, PRO2206
Ligand-3633-UYB
ILE2226, VAL2227
Ligand-3641-4YB
NLN2275, THR2277, PRO2296, LEU2298, PRO2229, PHE2279, ASN2301, TYR2483, 2MA3684, 0MA3685
Ligand-3646-OMA
ILE2283, ARG2292, PRO2296
Ligand-3648-UYB
THR2287, NLN2288, THR2290, LYS2291, PHE2293, LEU2355, HIS2459, ARG2460
Ligand-3653-OYB
TRP2366, ARG2372
Ligand-3654-2MA
PHE2354, LEU2355, ASN2362, SER2369, GLU2370, PHE2371, ARG2372, ASP2352, ALA2457, LEU2458, HIS2459
Ligand-3656-OfA
THR2287, ARG2460
Ligand-3657-4YB
NLN2336, THR2338, ASN2339, VAL2341, LYS2343, VAL2385
Ligand-3664-UYB
TYR2359, TYR2374, SER2375, NLN2363, SER2376, ALA2377, ASN2378
Ligand-3669-2MA
GLU2346, NLN2379
Ligand-3671-OfA
LYS2361, ASN2362, NLN2363
Ligand-3672-UYB
ARG1440, NLN2379
Ligand-3677-2MA
THR1439, ARG1440, LYS1538, GLY1541, ASN1542, TYR1543
Ligand-3679-OfA
ARG1440, NLN2379, CYS2380
Ligand-3686-2MA
LYS1552, SER1553, ASN1554, LEU1555, LYS1556, THR2450, 4YB3680, VMA3683, 2MA3684
Ligand-3688-2MA
ARG1551, LYS1552, ILE1566, GLN1568, ALA1569, GLY1570, SER1571, THR1572, PRO1573, CYS1574, ASN1575, GLY1576, ASN1581, VMB3682
Ligand-3690-UYB
SER1649, ASN1650, LYS1651, LYS1652, PHE1653, LEU1654, GLU1677, PHE2257, NLN2496, GLY2497
Ligand-3696-2MA
GLU1648, SER1649, ASN1650
Ligand-3699-UYB
NLN2545, GLN2794, THR2795
Ligand-3706-OfA
THR2547
Ligand-3707-UYB
PHE2556, NLN2557, ALA2558, THR2559, ARG2560, SER2587, PHE2588, TRP2650, ASN2653, ASN2654, LEU2655, ASP2656, SER2657, LYS2658, VAL2659, ARG2723
Ligand-3714-OfA
GLU2554, NLN2557, ALA2558, THR2559
Ligand-3715-4YB
ILE1663, SER2519, THR2521, GLU2523, THR2816, NLN2817
Ligand-3720-OMA
SER2260, LYS2492, TYR2493, ASN2494, GLU2495, THR2500
Ligand-3721-OMA
ILE1663, LEU2517, LYS2518, SER2519, LEU2262
Ligand-3722-UYB
NLN2830, CYS2831, THR2832, ASP2841, GLN2842, THR2846, TRP2847, PHE2857, GLN2858, THR2859, ARG2860, HIS2869, NLN2871, ILE2884, THR2910
Ligand-3727-2MA
ARG2848, GLU2868, HIS2869, VAL2870, NLN2871
Ligand-3729-OfA
GLN2858, THR2859, ARG2860
Ligand-3730-4YB
PRO783, SER784, LYS785, PRO786, LYS788, NLN2871, ASN2872, SER2873
Ligand-3735-OMA
SER784
Ligand-3736-2MA
LYS764, PRO783, LYS788, GLN846, GLU2916
Ligand-3738-4YB
SER2922, NLN2923, ASN2924
Ligand-3745-4YB
THR2930, NLN2931, PHE2932, GLU3132, ASN3133, LEU3136, LYS3287, PHE3323, TYR3324
Ligand-3750-OMA
ASP3360
Ligand-3751-OMA
LYS2180, GLY2218, ASN2219, GLU3325, ASP3360
Ligand-3752-4YB
LYS3009, ASP3010, NLN3015, SER3017, GLN3018, PHE3031, ASN3142, ILE3145, GLY3146, GLN3149, ASP3150, SER3153, SER3154
Ligand-3759-4YB
NLN3288, PHE3289, THR3290, SER3311, NLN3312
Ligand-3766-4YB
LYS3287, PHE3289, NLN3312, PHE3317, TYR3324, PRO3326
Ligand-3773-UYB
CYS3296, HIS3297, ASP3298, GLY3299, NLN3348, ASN3349, THR3350
Ligand-3778-2MA
GLU1118, LEU1119, ASP1120
Ligand-3780-OfA
CYS3296, ASP3298, GLY3299, NLN3348
ARG24.NE-ASP67.OD1 26.33
ILE71.N-TYR177.O 25.33 TYR381.OH-GLU501.OE1 25.33
TYR164.N-TYR120.O 37.50
TYR493.N-ILE387.O 37.33
ASN433.ND2-ASP427.O 57.17
PHE377.N-VAL509.O 56.50
THR310.N-TYR291.O 26.17
GLN279.NE2-ASN281.OD1 19.00
ASN63.ND2-GLU185.OE2 18.17
ARG264.NH1-ASP287.OD1 17.33
ARG264.NH2-ASP287.OD2 23.50 THR249.N-ILE254.O 23.33 CYX101.N-LEU182.O 23.17 TYR256.N-GLY247.O 23.17
SER35.OG-ASP33.OD2 35.33
VAL312.N-ALA289.O 35.00
ILE27.N-VAL64.O 35.00
ARG250.N-ASN229.O 34.83
SER218.N-SER204.O 34.33
GLN162.N-TYR122.O 34.17
ARG126.NH1-SER128.O 34.17
ASN229.N-GLN162.OE1 51.83
ASP427.N-SER423.O 50.67
ASP67.N-VAL181.O 50.50
VAL276.N-CYX219.O 50.50
ASP111.N-SER107.O 49.83
LEU124.N-PRO160.O 49.17
SER107.N-PRO176.O 33.33
SER35.OG-ASP33.OD1 33.17
GLN491.NE2-ASN486.O 47.50
ASP89.N-GLY85.O 46.50
VAL209.N-THR313.O 22.50 GLN459.NE2-GLY461.O 22.33
ARG340.NH2-ASP383.OD1 16.83
THR249.OG1-ARG251.O 16.83
ARG251.NH1-GLU153.OE2 17.00
THR275.N-ASP270.O 17.00
TYR65.OH-GLU185.OE2 17.00
VAL193.N-PHE61.O 22.83 THR400.OG1-ASP405.OD2 22.83 ARG269.NH2-GLY252.O 22.50
ASP287.N-LYS284.O 33.67
GLY223.N-GLN167.OE1 33.67
ILE387.N-TYR493.O 33.50
VAL181.N-ASP67.O 47.83
ASN29.N-THR192.OG1 17.00
ASN379.ND2-GLU501.OE2 17.17
ARG24.NH2-ASP67.OD1 17.33
ASN424.N-ASN422.OD1 17.50
ALA420.N-THR361.O 17.50
GLY389.N-GLN491.O 17.50
CYX321.N-VAL347.O 23.17
TYR256.OH-ASP296.OD2 23.50
ASP270.N-THR275.O 47.50
VAL496.N-ILE419.O 48.17
ARG251.NH1-GLU153.OE1 17.33
ARG340.NH2-ASP383.OD2 23.67
ASN422.ND2-GLN491.OE1 35.33
ASP383.N-VAL497.O 52.00
SER358.OG-PRO302.O 51.83 SER183.N-TYR65.O 23.67
LYS25.N-ALA66.O 17.83 GLY100.N-TYR49.O 17.67 ARG126.NE-ASP136.OD1 17.50
SER18.OG-LEU121.O 24.17 ALA144.N-ASN156.O 23.83 LYS363.N-VAL418.O 23.83
GLN279.N-THR266.O 35.67
SER423.N-PRO492.O 35.50
TYR158.N-TYR142.O 35.50
ARG123.NH1-ASP136.OD1 18.00
SER107.OG-ASP111.OD2 18.00
TYR234.OH-ASP296.OD2 18.17
VAL180.N-ILE103.O 52.67
ARG264.NH2-ASP287.OD1 24.17
SER356.OG-VAL352.O 25.00
VAL418.N-LYS363.O 52.17
ASN117.ND2-ASP111.O 53.17
ALA258.N-VAL245.O 18.00
CYX417.N-LEU498.O 24.17
TYR158.OH-ASP296.OD1 35.67
VAL31.N-ASN3.O 35.67
LEU130.N-ASP89.O 53.50
GLN143.NE2-GLY145.O 24.33 LYS47.N-VAL102.O 24.17
LEU498.N-CYX417.O 36.00
ILE103.N-VAL180.O 35.83
VAL102.N-LYS47.O 54.33
ARG494.NH2-ASP427.OD1 53.50
LEU446.N-ASP405.O 53.33
SER204.N-SER218.O 18.00
ARG178.N-TRP105.O 24.67
SER315.N-VAL209.O 36.50
LYS284.N-ASP287.OD2 36.50
ARG123.N-ASN91.OD1 55.67
ARG126.NE-ASP136.OD2 18.33 NLN12.N-GLY8.O 18.33
TRP233.N-ALA246.O 54.33
TYR118.OH-GLY115.O 25.00
ARG264.NH1-ASP287.OD2 36.83
THR266.N-GLN279.O 36.67
TYR277.N-SER268.O 55.83
TRP421.N-ARG494.O 18.33
SER334.OG-LEU437.O 18.50
GLY416.N-TYR365.O 18.50
VAL314.N-THR288.OG1 18.67
ASN39.N-SER35.O 18.67
LYS341.N-ALA382.O 19.00
ARG494.NE-ASP427.OD2 55.83
TYR38.OH-PRO53.O 25.67
SER138.OG-GLU140.OE1 26.00
ARG24.NE-ASP67.OD2 26.17
MET280.N-LEU215.O 38.33
SER428.OG-ASN424.O 37.83
ALA295.N-GLN198.OE1 37.50
ARG439.N-ASN407.OD1 62.67
TYR291.OH-ASP287.O 62.67
CYX5.N-VAL31.O 26.17
TYR291.N-THR310.O 57.33
TYR142.N-TYR158.O 38.50
TYR122.N-GLN162.O 38.33
TYR436.OH-ASP427.OD1 64.83
SER423.OG-ASP427.OD2 63.17
Table 7.9 The HBs (with more than 10.00% occupancy rates) of the spike-trimer 600 frames’ MD file “production_Nb6cRBD1.pdb” PHE159.N-ASN229.OD1 13.33
(continued)
GLN394.NE2-GLU391.OE2 11.00
ALA460.N-ASN472.O 11.00
GLN483.NE2-THR485.OG1 11.00
ASN57.ND2-ASP33.OD1 11.17
SER222.OG-ASN170.OD1 11.33
ALA294.N-GLY232.O 11.33
TYR142.OH-ALA298.O 11.50
ASN229.ND2-PHE159.O 11.50
ARG126.NH2-ASP136.OD1 11.50
VAL468.N-CYX465.O 11.67
ALA88.N-GLN78.OE1 11.67
SER68.N-ASN23.O 12.00
THR62.N-GLU185.O 12.00
GLU243.N-ARG235.O 12.00
GLN394.NE2-GLU391.OE1 12.17
LYS447.N-GLU450.OE1 12.17
LYS93.NZ-ASP89.OD2 12.33
LEU37.N-TYR34.O 12.33
LEU503.N-THR378.OG1 12.67
TYR234.OH-ASP296.OD1 12.67
SER360.N-ALA420.O 12.67
SER268.N-TYR277.O 12.67
PHE500.N-THR415.O 12.67
SER384.N-ASN339.O 12.67
ARG442.NE-ASP452.OD1 12.83
THR62.OG1-PRO190.O 12.83
ARG123.NH1-ASP136.OD2 13.00
LYS113.N-PHE166.O 13.00
ARG439.NH2-SER454.O 13.17
ARG135.NH1-TRP22.O 13.17
Supplementary Information 321
ALA66.N-LYS25.O 32.67
CYX473.N-GLY470.O 32.50
TYR458.N-TYR474.O 32.33
TYR92.OH-ASP67.OD1 32.33
TYR92.OH-ASP67.OD2 32.00
TYR438.N-GLN478.O 31.33
TYR164.OH-GLU75.OE1 31.33
TYR408.N-ILE403.O 31.33
ARG340.NE-ASP383.OD1 31.17
ILE419.N-VAL496.O 31.00
GLY154.N-CYX157.O 30.83
ASN355.N-SER351.O 30.67
THR508.N-PHE377.O 30.67
VAL495.N-PHE385.O 30.50
ALA382.N-LYS341.O 30.50
ASN274.ND2-GLY115.O 30.33
LEU278.N-LEU217.O 29.17
SER112.OG-ASN108.O 29.00
THR288.OG1-PRO285.O 28.67
VAL179.N-PHE69.O 28.67
ASN433.N-PHE482.O 28.33
TYR158.OH-ASP296.OD2 28.17
ILE248.N-MET231.O 28.00
ALA32.N-CYX194.O 28.00
ASN91.ND2-ARG123.O 27.83
SER351.OG-ASP349.OD1 27.83
SER454.OG-ASP452.OD1 27.50
TYR474.N-TYR458.O 27.33
ASP296.N-ALA230.O 27.17
ARG235.N-GLU243.O 27.17
LEU440.N-PRO476.O 26.83
SER138.OG-GLU140.OE2 26.67
TYR480.N-TYR436.O 26.67
ARG494.N-TRP421.O 26.50
TYR408.OH-ASP383.OD1 26.50
THR275.OG1-LYS273.O 26.33
SER107.OG-ASP111.OD1 46.33
TYR234.N-TYR292.O 46.00
TYR49.N-GLY100.O 46.00
TYR365.N-GLY416.O 45.83
VAL497.N-ASP383.O 45.67
PHE61.N-VAL193.O 45.67
PHE226.N-SER222.O 45.17
GLY212.N-LEU283.O 45.17
ALA348.N-CYX510.O 45.00
LEU217.N-LEU278.O 45.00
THR508.OG1-THR378.O 45.00
THR192.OG1-THR62.O 44.50
VAL245.N-TRP233.O 43.83
GLY232.N-ALA294.O 43.67
GLN175.NE2-ASN170.O 43.50
TYR120.OH-ASP111.OD2 43.50
ASP405.N-GLY401.O 43.50
TYR177.N-ILE71.O 42.67
ARG178.NH2-ASP111.OD2 42.50
TYR292.N-TYR234.O 42.17
TYR92.N-ILE87.O 41.50
ARG178.NE-ASP111.OD1 41.33
VAL347.N-ASN319.O 41.17
TYR381.N-SER499.O 41.17
ILE343.N-VAL380.O 40.33
SER454.OG-ASP452.OD2 40.17
SER351.OG-ASP349.OD2 39.83
TYR65.N-SER183.O 39.67
TYR256.OH-ASP296.OD1 39.67
GLN478.N-TYR438.O 39.33
ARG442.NH1-SER444.O 39.33
TYR408.OH-ASP383.OD2 39.17
ASN106.ND2-GLN175.OE1 39.17
THR192.N-PHE61.O 39.00
LEU182.N-CYX101.O 39.00
TYR354.OH-ASN373.OD1 39.00
Table 7.9 (continued)
ARG340.NE-ASP383.OD2 19.17
PHE449.N-LYS409.O 19.17
TRP105.N-ARG178.O 19.17
MET231.N-ILE248.O 19.17
THR84.OG1-ASP89.OD2 19.33
SER112.OG-ASN108.OD1 19.33
TYR65.OH-GLU185.OE1 19.33
THR400.OG1-ASP405.OD1 19.33
GLN78.N-GLU75.O 19.50
ASN424.ND2-PRO484.O 19.50
ASN108.N-ASN106.OD1 19.67
TYR120.OH-ASP111.OD1 19.83
ASN379.ND2-GLU501.OE1 19.83
GLY73.N-GLN175.O 19.83
LEU215.N-MET280.O 19.83
VAL509.N-PHE377.O 20.00
TYR381.OH-GLU501.OE2 20.00
SER299.OG-SER358.OG 20.17
THR84.OG1-ASP89.OD1 20.33
ASN407.ND2-ARG439.O 20.33
ASN117.N-PHE166.O 20.33
ALA220.N-VAL202.O 20.50
GLY247.N-TYR256.O 20.50
THR313.N-GLY207.O 20.50
TYR493.OH-VAL488.O 20.67
LEU283.N-GLY213.O 20.67
PHE133.N-LYS93.O 20.83
VAL202.N-ALA220.O 20.83
ARG451.NH1-TRP338.O 21.00
ARG24.NH2-ASP67.OD2 21.17
GLN394.N-GLU391.O 21.17
NLN328.N-GLY324.O 21.33
TYR164.OH-GLU75.OE2 21.33
ARG439.NH2-ASP452.O 22.00
ALA104.N-THR45.O 22.00
VAL386.N-ALA333.O 22.17
VAL380.N-ILE343.O 13.50
ARG388.NH1-ASP390.OD2 13.50
LYS447.N-GLU450.OE2 13.50
SER428.OG-ASN424.OD1 13.50
LEU426.N-SER423.O 13.67
CYX219.N-VAL276.O 13.67
ASP74.N-GLY173.O 13.67
ASN345.N-THR508.OG1 13.83
ASP390.N-GLY489.O 13.83
ARG388.NE-ASP390.OD1 14.00
GLN236.N-VAL290.O 14.17
ARG123.NH2-GLU140.OE1 14.33
ASN229.ND2-LEU161.O 14.33
ASN57.ND2-ASP33.OD2 14.33
TYR434.OH-GLY431.O 14.33
TRP421.NE1-TYR305.OH 14.83
ARG123.NH2-GLU140.OE2 15.00
LYS86.NZ-LEU124.O 15.33
SER40.OG-VAL36.O 15.33
ILE267.N-TYR257.OH 15.33
ARG178.NH2-ASP111.OD1 15.33
PHE265.N-VAL261.O 15.33
ARG251.NE-GLU153.OE2 15.50
GLU185.N-ASN63.O 15.50
VAL70.N-ALA17.O 15.50
ALA404.N-GLN394.OE1 15.83
GLU501.N-ASN379.O 15.83
ARG269.NH1-THR249.O 15.83
PHE327.N-PHE323.O 16.00
SER499.N-TYR381.O 16.17
VAL64.N-ILE27.O 16.17
GLY470.N-CYX473.O 16.17
SER138.N-TYR20.OH 16.50
LYS429.N-PHE482.O 16.50
SER163.N-GLY227.O 16.67
ASN63.ND2-GLU185.OE1 16.67
ARG264.NH2-SER260.O 9.50
ILE395.N-VAL392.O 9.50
ALA221.N-ASN274.O 9.50
TYR438.OH-GLN478.OE1 9.67
LYS93.NZ-ASP89.OD1 9.67
THR62.OG1-GLU185.OE2 9.67
THR139.N-GLU140.OE2 9.83
ARG178.NE-ASP111.OD2 9.83
GLY85.N-ASP89.OD1 10.00
GLN483.N-ASN486.OD1 10.00
ARG77.NH2-ASP74.OD2 10.00
LEU372.N-SER368.O 10.17
SER479.OG-TYR434.O 10.17
ARG126.NH2-ASP136.OD2 10.17
LEU437.N-SER334.OG 10.33
ASN379.N-GLU501.O 10.50
ARG251.NE-GLU153.OE1 10.50
GLN200.NE2-THR169.O 10.50
TYR34.N-ASN57.OD1 10.67
VAL261.N-ALA258.O 10.67
ASN425.ND2-TRP306.O 10.67
ARG228.NH1-ASP304.OD2 10.83
ALA357.N-SER299.OG 11.00
322 7 Spike (S) Glycoprotein
Supplementary Information Table 7.10 The SBs of the spike aa ASN1-LYS195 100 frames’ (with frame stride = 10) MD files of [258]
323 MD-rep2
MD-rep3
MD-rep4
Optimized model
ASP109-ARG176
ASP109-ARG176
ASP109-ARG176
ASP109-ARG176
ASP134-ARG121
ASP134-ARG121
ASP134-ARG121
ASP134-ARG121
ASP134-ARG124
ASP134-ARG124
ASP134-ARG124
ASP134-ARG124
ASP31-LYS195
ASP31-LYS195
ASP31-LYS195
ASP56-LYS195
ASP56-LYS195
ASP56-LYS195
ASP56-LYS195
ASP56-LYS53
ASP56-LYS53
ASP56-LYS53
ASP56-LYS53
ASP65-ARG22
ASP65-ARG22
ASP65-ARG22
ASP65-ARG22
ASP72-ARG70
ASP72-ARG70
ASP72-ARG70
ASP72-ARG70
ASP72-ARG75
ASP72-ARG75
ASP72-ARG75
ASP72-LYS84
ASP72-LYS84
ASP72-LYS84
ASP87-LYS91
ASP87-LYS91
ASP87-LYS91
ASP94-LYS91
ASP94-LYS91
GLU132-ARG124
GLU132-ARG124
ASP87-LYS84
ASP87-LYS84
GLU132-LYS129
ASP94-LYS91 GLU132-ARG124
GLU132-LYS129
GLU132-LYS129
GLU138-ARG121
GLU138-ARG121
GLU138-ARG121
GLU138-ARG124
GLU138-ARG124 GLU138-LYS125
GLU138-LYS125
GLU132-ARG124
GLU138-LYS125
GLU138-ARG13 GLU138-ARG133 GLU151-ARG121 GLU151-ARG124 GLU151-LYS111 GLU151-ARG70
GLU151-ARG70
GLU151-LYS84
GLU151-ARG70 GLU151-LYS125
GLU151-LYS125 GLU151-LYS84
GLU151-LYS84
GLU183-ARG24
GLU183-ARG24
GLU183-ARG24
GLU73-ARG70
GLU73-ARG70
GLU73-ARG70
GLU73-ARG75
GLU73-ARG75
GLU73-ARG75
GLU73-LYS84
GLU73-LYS84
GLU73-LYS84
GLU7-LYS23
GLU7-LYS23
GLU7-LYS23
GLU7-ARG13
324
7 Spike (S) Glycoprotein
Table 7.11 The HBs (with more than 10% occupancy rates) of the spike aa ASN1-LYS195 100 frames’ (with frame stride = 10) MD files of [258] Rep2
Rep3
Rep4
LEU180.N-CYX99.O 57%
ASP87.N-GLY83.O 53%
SER105.OG-ASP109.OD1 49%
VAL178.N-ILE101.O 52%
SER16.OG-LEU119.O 53%
TYR118.OH-ASP109.OD2 49%
TYR175.N-ILE69.O 51%
VAL100.N-LYS45.O 51%
ILE69.N-TYR175.O 48%
CYX3.N-VAL29.O 49%
VAL179.N-ASP65.O 50%
SER38.OG-VAL34.O 48%
VAL100.N-LYS45.O 48%
VAL178.N-ILE101.O 47%
VAL100.N-LYS45.O 47%
SER33.OG-ASP31.OD2 48%
ILE69.N-TYR175.O 45%
ASP87.N-GLY83.O 45%
ASP87.N-GLY83.O 46%
CYX3.N-VAL29.O 44%
VAL178.N-ILE101.O 45%
SER105.OG-ASP109.OD1 46%
ALA64.N-LYS23.O 42%
SER16.OG-LEU119.O 45%
ARG121.N-ASN89.OD1 45%
TYR175.N-ILE69.O 42%
VAL179.N-ASP65.O 44%
ILE69.N-TYR175.O 42%
VAL68.N-ALA15.O 41%
TYR36.N-TYR32.O 44%
ALA102.N-THR43.O 41%
LEU128.N-ASP87.O 40%
ALA64.N-LYS23.O 44%
TYR47.N-GLY98.O 41%
PHE59.N-VAL191.O 40%
TYR120.N-GLN160.O 43%
ARG176.N-TRP103.O 40%
ASP65.N-VAL179.O 39%
ARG22.NE-ASP65.OD2 43%
ASP65.N-VAL179.O 40%
TYR47.N-GLY98.O 38%
LEU180.N-CYX99.O 42%
ARG22.NH2-ASP65.OD2 40%
GLN160.N-TYR120.O 38%
ARG121.N-ASN89.OD1 39%
VAL29.N-ASN1.O 39%
ARG121.N-ASN89.OD1 37%
TYR90.N-ILE85.O 39%
SER66.N-ASN21.O 39%
TYR162.N-TYR118.O 37%
VAL177.N-PHE67.O 38%
ILE25.N-VAL62.O 39%
ARG176.N-TRP103.O 36%
TYR162.N-TYR118.O 38%
VAL179.N-ASP65.O 39%
ARG176.NH2-ASP109.OD1 36%
TYR47.N-GLY98.O 38%
ARG22.NE-ASP65.OD1 38%
TYR162.OH-GLU73.OE1 35%
VAL68.N-ALA15.O 38%
TYR63.N-SER181.O 37%
TYR90.N-ILE85.O 35%
ARG176.N-TRP103.O 38%
ALA30.N-CYX192.O 36%
GLU183.N-ASN61.O 35%
GLN160.N-TYR120.O 36%
PHE9.N-PHE5.O 36%
ILE101.N-VAL178.O 34%
SER66.N-ASN21.O 35%
ALA64.N-LYS23.O 36%
SER105.OG-ASP109.OD2 34%
ARG22.NE-ASP65.OD1 34%
VAL177.N-PHE67.O 35%
TYR162.OH-GLU73.OE2 34%
SER110.OG-ASN106.O 34%
LEU122.N-PRO158.O 33%
SER33.OG-ASP31.OD1 34%
VAL29.N-ASN1.O 34%
PHE59.N-VAL191.O 33%
LEU180.N-CYX99.O 33%
TYR162.OH-GLU73.OE1 34%
LYS45.N-VAL100.O 33%
ALA30.N-CYX192.O 33%
ILE101.N-VAL178.O 33%
TYR118.OH-ASP109.OD2 33%
TYR36.OH-PRO51.O 33%
TYR175.N-ILE69.O 33%
TYR90.OH-ASP65.OD2 32%
ARG22.NE-ASP65.OD1 32%
TYR90.OH-ASP65.OD1 33%
TYR162.N-TYR118.O 30%
ALA102.N-THR43.O 32%
ILE25.N-VAL62.O 33%
TRP103.N-ARG176.O 30%
SER105.OG-ASP109.OD1 32%
TYR162.OH-GLU73.OE2 33%
GLN160.N-TYR120.O 29%
VAL177.N-PHE67.O 31%
ASP65.N-VAL179.O 31%
ASN89.ND2-ARG121.O 29%
TYR90.OH-ASP65.OD2 30%
LEU128.N-ASP87.O 30%
TYR120.N-GLN160.O 29%
TRP103.N-ARG176.O 30%
TRP103.N-ARG176.O 30%
ARG176.NE-ASP109.OD1 29%
ASP109.N-SER105.O 29%
PHE131.N-LYS91.O 29%
ILE101.N-VAL178.O 28%
LYS23.N-ALA64.O 29%
ARG22.NH2-ASP65.OD1 29%
GLU183.N-ASN61.O 27%
TYR63.N-SER181.O 29%
LYS45.N-VAL100.O 29%
LYS23.N-ALA64.O 26%
ILE25.N-VAL62.O 29%
ARG176.NE-ASP109.OD1 29%
PHE131.N-LYS91.O 26%
VAL29.N-ASN1.O 29%
NLN10.ND2-GLY6.O 28%
SER181.N-TYR63.O 26%
ARG22.NE-ASP65.OD2 29%
ALA102.N-THR43.O 28%
VAL68.N-ALA15.O 26%
SER33.OG-ASP31.OD2 28%
SER33.OG-ASP31.OD1 28%
ARG176.NH2-ASP109.OD2 26%
THR190.OG1-THR60.O 28%
SER181.N-TYR63.O 27%
ALA11.N-GLU7.O 26%
ARG176.NE-ASP109.OD1 28%
PHE9.N-PHE5.O 27%
TYR90.OH-ASP65.OD1 24%
TYR18.OH-ASP134.OD1 28%
LYS23.N-ALA64.O 26%
ARG22.NE-ASP65.OD2 24%
ARG121.NH1-PHE123.O 27%
ARG22.NH2-ASP65.OD2 26%
VAL191.N-PHE59.O 24%
ARG176.NE-ASP109.OD2 26%
ASP72.N-GLY171.O 26%
TYR63.OH-GLU183.OE2 24%
TYR120.N-GLN160.O 26%
ALA30.N-CYX192.O 25%
LEU54.N-SER50.O 23%
TYR18.OH-ASP134.OD2 26%
ASP109.N-SER105.O 25%
THR137.OG1-ASP134.O 23%
VAL191.N-PHE59.O 25%
TYR63.N-SER181.O 24%
ASP109.N-SER105.O 22%
ARG22.NH2-ASP65.OD2 25%
GLY98.N-TYR47.O 24%
SER33.OG-ASP31.OD1 22%
ARG176.NH2-ASP109.OD2 25%
ASN89.ND2-ARG121.O 23%
ASP31.N-CYX3.O 22%
ASP31.N-CYX3.O 25%
GLN76.N-GLU73.O 23%
GLY71.N-GLN173.O 22%
GLN76.N-GLU73.O 24%
SER33.OG-ASP31.OD2 23%
SER110.OG-ASN106.O 22%
TYR90.OH-ASP65.OD1 24%
TYR118.OH-ASP109.OD1 22%
TYR116.N-VAL112.O 22%
CYX99.N-LEU180.O 24%
CYX3.N-VAL29.O 22%
TYR162.OH-GLU73.OE1 21%
SER181.N-TYR63.O 24%
SER105.OG-ASP109.OD2 21%
THR190.OG1-THR60.O 21%
ARG22.NH2-ASP65.OD1 23%
TYR90.OH-ASP65.OD2 21%
LEU35.N-TYR32.O 21%
GLY71.N-GLN173.O 22%
GLY71.N-GLN173.O 21%
ARG22.NH2-ASP65.OD1 21%
LYS129.N-GLU132.OE1 22%
CYX99.N-LEU180.O 21%
ASN104.ND2-GLN173.OE1 21%
ASN89.ND2-ARG121.O 22%
ILE85.N-GLN76.OE1 21%
CYX99.N-LEU180.O 21%
SER66.N-ASN21.O 22%
ASN104.ND2-GLN173.OE1 20%
NLN10.ND2-GLY6.O 21%
TYR118.OH-PHE14.O 22%
PHE59.N-VAL191.O 20%
TYR90.N-ILE85.O 20%
TYR118.OH-ASP109.OD2 20%
LYS129.N-GLU132.OE1 19%
Supplementary Information
325
Table 7.12 The HBs (with more than 10% occupancy rates) of the spike aa ASN1-LYS195 100 frames’ (with frame stride = 10) MD files of [258] (continuation) Rep2
Rep3
Rep4
LEU128.N-ASP87.O 20%
NLN10.N-GLY6.O 20%
THR190.OG1-THR60.O 19%
VAL62.N-ILE25.O 20%
THR190.N-PHE59.O 20%
VAL112.N-LEU108.O 19%
GLN76.N-GLU73.O 20%
LYS91.NZ-ALA86.O 20%
ARG176.NH1-ASP109.OD2 19%
THR190.N-PHE59.O 20%
SER161.N-CYX147.O 20%
SER105.N-PRO174.O 18%
THR12.OG1-VAL8.O 20%
ASN104.ND2-GLN173.OE1 19%
GLU183.N-ASN61.O 18%
ASN21.ND2-ARG13.O 20%
GLY98.N-TYR47.O 19%
ASN37.N-SER33.O 18%
TYR162.OH-GLU73.OE2 19%
VAL62.N-ILE25.O 19%
LEU122.N-PRO158.O 18%
LYS91.NZ-ASP87.OD2 19%
GLN165.N-TYR172.O 19%
ARG176.NE-ASP109.OD2 18%
SER136.OG-ASP134.OD2 19%
SER110.OG-ASN106.O 19%
NLN10.N-GLY6.O 18%
SER105.N-PRO174.O 18%
PHE9.N-PHE5.O 19%
THR82.OG1-GLN76.O 18%
LEU57.N-LYS53.O 18%
SER136.OG-GLU138.OE2 19%
TYR120.OH-GLU73.OE1 18%
TYR118.OH-ASP109.OD1 17%
TYR118.OH-ASP109.OD1 18%
NLN10.ND2-SER38.O 18%
SER136.OG-ASP134.OD1 17%
ARG121.NH1-GLU138.OE1 18%
ARG176.NH2-ASP109.OD1 17%
GLY98.N-TYR47.O 17%
ARG70.NH2-GLY163.O 18%
SER136.OG-ASP134.OD2 17%
PHE5.N-ASP31.O 17%
LEU57.N-LYS53.O 18%
LEU57.N-LYS53.O 17%
PHE67.N-VAL177.O 17%
THR43.N-ALA102.O 18%
ARG176.NH2-ASP109.OD2 17%
GLY113.N-ASP109.O 17%
ALA142.N-GLU138.O 18%
THR43.N-ALA102.O 16%
SER105.OG-ASP109.OD2 16%
LEU35.N-TYR32.O 17%
ALA39.N-LEU35.O 16%
ARG176.NH2-ASP109.OD1 16%
ASP72.N-GLY171.O 17%
TYR120.OH-GLU73.OE2 16%
SER16.OG-LEU119.O 16%
ARG70.NE-GLU73.OE1 17%
THR60.N-GLU183.O 15%
THR43.N-ALA102.O 16%
LYS45.N-VAL100.O 17%
VAL62.N-ILE25.O 15%
TYR36.OH-PRO51.O 15%
SER105.N-PRO174.O 17%
PHE67.N-VAL177.O 15%
ASN61.ND2-GLU183.OE2 15%
ARG70.NE-GLU73.OE2 17%
TYR18.OH-ASP134.OD1 15%
TYR90.N-ALA86.O 15%
ARG176.NH2-THR12.O 16%
LEU54.N-SER50.O 14%
ASN89.ND2-ILE85.O 15%
ILE85.N-GLN76.OE1 15%
LEU35.N-ASP31.O 14%
VAL112.N-LEU108.O 15%
SER110.OG-ASN106.OD1 15%
ARG70.NE-GLU73.OE1 14%
TYR63.OH-GLU183.OE1 14%
ASN106.N-ASN104.OD1 15%
TYR18.OH-ASP134.OD2 14%
ARG176.NE-ASP109.OD2 14%
ARG70.NH1-GLU73.OE1 15%
ARG124.NH1-GLU132.OE1 13%
ASN27.N-THR190.OG1 14%
ARG124.NH2-SER126.O 15%
ARG70.NE-GLU73.OE2 13%
SER161.OG-ASN117.OD1 14%
THR145.OG1-LEU159.O 15%
THR60.OG1-ALA187.O 13%
ARG124.NH1-SER126.O 13%
ARG121.NH1-GLU138.OE2 14%
TYR118.N-GLY114.O 13%
ASN115.N-PHE164.O 13%
TYR120.OH-GLU73.OE1 14%
SER42.N-ALA102.O 13%
ARG124.NE-SER126.O 13%
LEU54.N-SER50.O 13%
ARG70.NH1-GLU73.OE1 13%
THR60.N-GLU183.O 13%
ARG121.NH2-GLU138.OE1 13%
ARG121.NH2-GLU138.OE2 13%
PHE182.N-THR97.O 13%
GLN173.NE2-THR167.O 13%
ARG121.NH2-GLU138.OE1 13%
TYR140.N-SER136.O 13%
CYX28.N-THR190.O 13%
ARG121.NH2-PHE123.O 13%
SER40.OG-ASN37.O 13%
ARG24.NE-ASN61.OD1 13%
THR190.N-PHE59.O 12%
TYR140.N-TYR156.O 12%
ASN61.ND2-GLU183.OE1 13%
LYS129.N-GLU132.OE2 12%
THR82.OG1-ASP87.OD2 12%
LYS91.NZ-LEU128.O 13%
GLN160.NE2-PHE157.O 12%
ASN115.ND2-ASP109.O 12%
VAL112.N-LEU108.O 13%
PHE59.N-CYX28.O 12%
LYS129.N-GLU132.OE1 12%
NLN10.ND2-GLY6.O 12%
LYS91.NZ-LEU128.O 11%
ASN61.N-GLU183.O 12%
LYS129.N-GLU132.OE2 12%
ARG124.NH2-SER126.O 11%
ARG70.NE-GLU73.OE1 12%
PHE5.N-ASP31.O 12%
ASN117.N-GLY113.O 11%
ASN61.ND2-GLU183.OE1 12%
GLU132.N-LYS129.O 12%
THR12.OG1-VAL8.O 11%
GLN173.NE2-ASN168.O 12%
TYR63.OH-GLU183.OE1 12%
SER40.OG-TYR36.O 11%
ASN37.N-SER33.O 12%
GLN141.N-THR137.O 12%
GLN160.NE2-THR145.O 11%
ARG124.NH2-SER126.O 12%
ARG176.NH1-ALA11.O 11%
SER136.OG-ASP134.OD1 10%
ASP72.N-GLY171.O 11%
PHE131.N-LYS91.O 11%
SER110.OG-ASN106.OD1 10%
ALA86.N-GLN76.OE1 11%
THR60.OG1-ALA187.O 11%
ASN61.ND2-GLU183.OE1 10%
TYR18.OH-ASP134.OD2 11%
ASN127.ND2-ASP87.OD2 11%
ARG124.NH1-GLU132.OE2 10%
ARG75.NH1-ASP72.OD2 11%
ARG70.NH1-GLU73.OE2 11%
SER161.OG-TYR116.O 10%
ARG133.NH1-TRP20.O 11%
ASN61.ND2-GLU183.OE2 10%
ASP56.N-LYS53.O 10%
LYS129.N-GLU132.OE2 11%
THR82.OG1-ASP87.OD2 10%
ARG124.NE-ASP134.OD2 10%
SER38.OG-LEU35.O 11%
ASN37.N-SER33.O 10%
GLN165.N-TYR172.O 10%
GLN165.N-TYR172.O 11%
ARG124.NE-ASP134.OD1 10%
ARG124.NH2-GLU132.OE2 10%
TYR18.OH-CYX155.O 11%
GLY83.N-ASP87.OD2 10%
ARG121.NH1-GLU138.OE1 10%
TYR156.N-TYR140.O 10%
ARG133.NH2-TRP20.O 10%
ARG124.NH2-ASP134.OD1 10%
ARG124.NH1-GLU132.OE1 10%
ARG124.NH2-GLU132.OE2 10%
SER136.OG-ASP134.OD1 10%
ASN104.N-SER42.OG 10%
ARG124.NE-SER126.O 10%
CYX28.N-THR190.O 10%
ARG75.NH2-ASP72.OD1 10%
THR12.N-VAL8.O 10%
ARG121.NE-ASP134.OD1 10%
TYR172.N-ASN168.OD1 10%
ARG70.NH1-GLU151.OE2 10% PHE67.N-VAL177.O 10% ALA11.N-GLU7.O 10%
Chapter 8
Spike (S) Glycoprotein D614G Mutant
Abstract Recently, the SARS-CoV-2 D614G mutant has been reported to be potentially more transmissible (“contagious”) than its wild-type. When there is no laboratory structure for the mutant, we made two homology ones (with close and open spikes, respectively). In this brief chapter, we will give a note on the two (6vxx-, 6vyb-) homology structures for D614G mutant and present a comparison with its wild-type SARS-CoV-2. We found the mutant has stronger hydrogen bonds between GLY614 and ALA647 in each monomer and changed the molecular structure at residue ASN616. MD studies find that the D614G mutant produced new strong hydrogen bonds between ALA845 and GLY614. Keywords SARS-CoV-2 D614G mutant · More contagious · Homology structures · Structural bioinformatics · Compared with wild-type
8.1 Introduction Several recent papers [37, 83, 185, 186, 429] caused world attentions to the D614G mutant of SARS-CoV-2. It has been reported the mutant is more contagious than its wild-type virus. When its laboratory NMR, X-ray, or cryo-EM structures are not determined yet, we made two homology structures. This brief chapter is to do homology modeling first to get two molecular structures for the D614G mutant and then gives a note of preliminary analyses of their structural bioinformatics. A comparison with its wild-type will also be given in this brief chapter.
8.2 Homology Structures of D614G Mutant For 6vxx.pdb (structure of the SARS-CoV-2 spike (S) glycoprotein (closed state)) and 6vyb.pdb (SARS-CoV-2 spike ectodomain structure (open state)) downloaded from the Protein Data Bank (https://www.rcsb.org/), we used the Swiss-PdbViewer © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_8
327
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8 Spike (S) Glycoprotein D614G Mutant
4.1.0 (https://spdbv.vital-it.ch/) [133, 134] (a free package for comparative protein modeling) to make a mutation of residue 614 from aspartic acid (D) into glycine (G) for A, B, and C chains, respectively. Then we used Maestro 10.1 (Academic Use Only) (https://www.schrodinger.com/maestro) to optimize the models: “Edit.→Select Atoms.→All” and then “Tools.→Minimize.→All Atoms” for 100 cycles (backbone RMSD values between the unoptimized and optimized models are 0.450160 Åand 0.464231 Å, respectively, for the close and open models). We denote the models as 6vxx-close-D614G-mutant and 6vyb-open-D614G-mutant, respectively.
8.3 Structural Bioinformatics of D614G Mutant The noncovalent interactions of hydrogen bonds (HBs), salt bridges (SBs), van der Waals (vdWs) contacts, and hydrophobic (HYD) interactions are driving a protein to be able to perform its biological functions. In the below, we will find out the HBs, SBs, HYD interactions, and vdWs contacts of the 6vxx-close-D614G-mutant and 6vyb-open-D614G-mutant models.
8.3.1 6vxx-Close-D614G-Mutant In Sect. 7.3.1 for the trimeric SARS-CoV-2 S wild-type 6vxx-close-model, our analyses of the molecular dynamics (MD) trajectories data of 10 .μs confirm us: (1) SBs: – In each chain: ASP442-ARG509, ASP53-LYS195, ASP389-LYS528, ASP398-ARG355, GLU1031-ARG1039, ASP820-ARG815, GLU583LYS535, GLU96-ARG190, GLU324-LYS537, ASP820-LYS811, ASP663LYS310, GLU773-ARG1019, ASP775-LYS733, GLU340-LYS356, ASP578-ARG328, ASP574-LYS557, ASP40-ARG44 – Among chains: A:GLU1031-B:ARG1039, B:GLU1031-C:ARG1039, C:GLU1031-A:ARG1039; A:ASP574-C:LYS854, B:ASP574-A:LYS854; C:GLU773-A:LYS974 (2) HBs: – In each chain: C:ASP442.OD1-C:ARG509.NE with occupancy rate 54.13% and B:ASP442.OD1-B:ARG509.NH2 with occupancy rate 53.45% – Among chains: B:PHE43.N-C:PHE565.O with occupancy rate 54.13% – with strong side-chain .π -.π stacking too – and C:TYR369.OHA:THR415.OG1 with occupancy rate 50.30%
8.3 Structural Bioinformatics of D614G Mutant
329
(3) .π -interactions: – 5 .π -cations: in each chain, TYR396-ARG.+ 355.NH2-PHE464, LYS.+ 1028.NZ-PHE1042, LYS.+ 278.NZ-PHE306, ARG.+ 44.NH2-HIS49 – 19 .π -.π stackings: in each chain, TYR1110-PHE1075, TYR1067-PHE906, PHE800-PHE898-PHE802-PHE1052/PHE927, TYR660-TYR695, HIS655PHE643, TYR612-PHE318, PHE275-PHE58, PHE92-TRP104 (2), PHE201-PHE106, HIS519-PHE565, PHE423-TRP353 (2), PHE377TYR369, TRP436-PHE374, PHE338-TYR365 For the 6vxx-close-D614G-mutant, for the SBs, we find 137 SBs, where ASP442-ARG509 is in each chain, GLU1031-ARG1039 exists not only among chains but also in each chain (C:GLU1031-C:ARG1039, B:GLU1031-B:ARG1039, A:GLU1031-A:ARG1039; C:GLU1031-B:ARG1039, B:GLU1031-A:ARG1039, A:GLU1031-C:ARG1039), C:ASP574-A:LYS854, A:ASP574-B:LYS854, but we cannot find C:GLU773-A:LYS974. For the HBs, we only consider HBs around the residue GLY614 and find the wild-type has a HB ASP614.N2-ALA647.OD2 in chains B and C, respectively, and ASP614.N1-ALA647.OD1 in chain A, with the distance 3.2 Å, and the mutant has the same HBs but with shorter distances 2.78, 2.77, and 2.79 Å, respectively. For the secondary structure changes of segment SER605-VAL620 (around the residue at 614), we find the mutation D614G changed Turn into Coil at residue ASN616 and changed the side-chain orientation of the critical residue GLU619 (Fig. 8.1) – the superposition backbone RMSD value is 0.273619 Å.
Fig. 8.1 The secondary structure changes around the residue ASN616 for the 6vxx-close-D614Gmutant model
Around the residue at 614, the .π -.π stackings such as PHE318-TYR612, TYR695-TYR660, and PHE643-HID655 are still being kept in each chain of the mutant.
8.3.2 6vyb-Open-D614G-Mutant In Sect. 7.3.2 for the trimeric SARS-CoV-2 S wild-type 6vyb-open-model, our analyses of the MD trajectories data of 10 .μs confirm us:
330
8 Spike (S) Glycoprotein D614G Mutant
(4) SBs: – In each chain: ASP442-ARG509, ASP820-ARG815, ASP578-ARG328, ASP820-LYS811, ASP467-ARG454, ASP53-LYS195, ASP663-LYS310, GLU583-LYS535, ASP775-LYS733, GLU773-ARG1019, GLU340LYS356, ASP574-LYS557, ASP40-ARG44, GLU1031-ARG1039, ASP1084-LYS1086, ASP571-ARG567, ASP405-ARG403, GLU465ARG457, GLU191-ARG34 – Among chains: A:GLU1031-B:ARG1039, B:GLU1031-C:ARG1039, C:GLU1031-A:ARG1039 (with weak SBs A:GLU1031-B:LYS1038, B:GLU1031-A:LYS1038, C:GLU1031-A:LYS1038); C:ASP574-B: LYS854; B:GLU773-C:ARG1014 (5) HBs: – In each chain: B:ARG509.NE-B:ASP442.OD2 with occupancy rate 58.44% and B:ARG509.NH2-B:ASP442.OD1 with occupancy rate 51.62%. – Among chains: A:PHE43.N-B:PHE565.O with occupancy rate 51.38%, B:PHE43.N-C:PHE565.O with occupancy rate 54.01%, and C:PHE43.NA:PHE565.O with occupancy rate 54.37% – between side chains of PHE43 and PHE565, there are strong .π -.π stackings too. (6) .π -interactions: – 7 .π -cations: in each chain, TYR396-Arg.+ 355.NH2-PHE464, Lys.+ 1028.NZPHE1042, Lys.+ 278.NZ-PHE306, Arg.+ 44.NH2-HIS49, Arg.+ 466.NH2TRP353, Lys.+ 1073.NZ-PHE1075 – 17 .π -.π stackings: in each chain, TYR1110-PHE1075, PHE800-PHE898PHE802-PHE1052/PHE927, TYR660-TYR695, PHE92-TRP104 (2), PHE201-PHE106, PHE423-TRP353 (2), PHE377-TYR369, TRP436PHE374, PHE58-PHE275, TYR495-TYR453, PHE515-PHE392, PHE192TRP104 For the 6vyb-open-D614G-mutant, for the SBs, we find 119 SBs, where ASP442ARG509 is in A and C chains, respectively, GLU1031-ARG1039 exists not only among chains but also in each chain (C:GLU1031-C:ARG1039, B:GLU1031B:ARG1039, A:GLU1031-A:ARG1039; C:GLU1031-B:ARG1039, B:GLU1031A:ARG1039, A:GLU1031-C:ARG1039), and A:GLU1017-B:ARG1019, C:GLU1017-A:ARG1019, B:ASP745-A:ARG319, A:ASP745-C:ARG319, C:GLU702-A:LYS790, A:GLU702-B:LYS790, B:ASP985-A:LYS386, A:ASP1118-C:ARG1091, A:ASP198-C:LYS462, and A:ASP994-C:ARG995 exist among ABC chains. In each chain, the SBs ASP53-LYS195, ASP663-LYS310, GLU583-LYS535, ASP775-LYS733, GLU773-ARG1019 (C and A), GLU340LYS356 (C and A), ASP574-LYS557, ASP40-ARG44, ASP1084-LYS1086, ASP571-ARG567 (C and A), ASP405-ARG403, GLU465-ARG457 (A), and GLU191-ARG34 are still existing. For the HBs, we only consider HBs around the residue GLY614 and find the wild-type has a HB ASP614.N2-ALA647.OD2 in chains B and C, respectively, with distances 3.06 and 3.10 Å, respectively, and
8.4 Concluding Remarks
331
ASP614.N1-ALA647.OD1 in chain A with the distance 3.09 Åand the mutant has the same HBs but with shorter distances 2.83, 2.75, and 2.84 Å, respectively. For the secondary structure changes of segment SER605-VAL620 (around the residue at 614), we find the mutation D614G changed Coil + 3.10 -helix + Coil into Turn in segment ASN616-VAL620 and changed the side-chain orientation of the critical residue GLU619 (Fig. 8.2) – the superposition backbone RMSD value is 0.209914 Å.
Fig. 8.2 The secondary structure changes around the residue ASN616 in C chain for the 6vybopen-D614G-mutant model
Around the residue at 614, the .π -cation LYS.+ 1073.NZ-PHE1075 and the .π -.π stackings such as PHE318-TYR612, TYR695-TYR660, and PHE643-HID655 are still being kept in each chain of the mutant. In [155], we were told the two adjacent residues ASP614 and ASN616 point in opposite directions, unlikely sharing a meaningful interaction. In [105, 200, 215, 244, 261, 399], we were told there exists a HB A:ASP614-B:THR859 linking S1 and S2 of spike (6vsb.pdb), but we have not found it yet from 6vxx.pdb and 6vyb.pdb (Fig. 8.3). The mutation at 614 from charged residue ASP into the residue GLY (which has higher degree of freedom and is commonly associated with Turns in a protein secondary structure and sometimes acts as a helix or other structure breaker) should reduce the surface of electrostatic negative charges around segment 614–620. We illuminate the Poisson-Boltzmann electrostatic potential surface of segment 605– 620 of the 6vxx-model and the 6vyb-model in Fig. 8.4 (where we should also notice the difference at residue 607 for the two models).
8.4 Concluding Remarks In this brief chapter, we found that (compared with the wild-type) the D614G mutant has stronger hydrogen bonds between GLY614 and ALA647 in each monomer and changed the molecular structure at residue ASN616. Furthermore, research on the mutant is clearly needed. The PDB entry 6M17 has F chain CYS336-LEU518; we cut 6VXX.pdb and only keep CYS336-LEU518 segment, and for A, B, and C chains, the RMSDs from 6M17.pdb’s F chain are 65.715129, 95.341880, and 76.302272 Å, respectively. Hence, it is difficult to do molecular modeling for the D614G mutant in complex
332
8 Spike (S) Glycoprotein D614G Mutant
Fig. 8.3 No HB A:ASP-614-B:THR859 linking S1 and S2 of spike in 6vxx-model and 6vybmodel (as in 6vsb.pdb)
with the human ACE2 in the use of PDB entries 6M17 and 6VXX. However, seeing Fig. 8.5, because in the spike the residue LYS417 in the RBD spans 197 residues to the residue 614 and in three-dimensional (3D) space they distance to each other very far (for the 6vxx-close-D614G-mutant model, the distance between A:GLY614.C and A:LYS417.C is 62.35 Å, and for the 6vyb-open-D614G-mutant model, the distance between C:GLY614.C and C:LYS417.C is 62.60 Å), we still may say that the polar contact LYS417-ASP30 of Chap. 7 between SARS-CoV-2 S and human ACE2 should still exist for the SARS-CoV-2 D614G mutant in complex with human ACE2.
8.4.1 Confirmed from Some MD Datasets In [114], the data files contain structures of the D614G mutant and its (closed) wild-type at 500 ns from MD simulations of closed SARS-CoV-2 spike protein embedded in POPC membrane. Firstly, we use these datasets to identify structural
8.4 Concluding Remarks
333
Fig. 8.4 The Poisson-Boltzmann electrostatic potential surface of segment 605–620 of the 6vxxmodel and the 6vyb-model (up, 6vxx-model; down, 6vyb-model; left, wild-type; right, D614G mutant)
perturbations of the D614G mutant from its wild-type. Seeing Fig. 8.6, we know the mutation made some local structural perturbations: (i) for A chain at ASN616 and CYS617 Coil changed into Turn, (ii) for B chain at residue 614 Extended conformation/isolated Bridge changed into Turn and at GLU619 Turn changed into .α-Helix, and (iii) for C chain at VAL615 Turn changed into isolated Bridge and at THR618 .α-Helix changed into Coil. The D614G mutation made the wild-type lost HBs THR859.OG1-ASP614.OD1 [105, 200, 215, 244, 261, 399], SER591.OGASP614.O, and ARG847.NE-ASP614.OD2 (with SB B:ASP614-C:ARG847), but produced a new HB CYS851.N-GLY614.O (where the residue CYS851 is in the middle of residues ARG847 and THR859). Cino [75] presented two sets of 200 ns MD trajectories, respectively, for the wild-type and D614G prefusion spike proteins (6VSB.pdb, single RBD in the up conformation) with site-specific glycans. The SARS-CoV-2 spike protein resides on the exterior surface of the coronavirus and undergoes dramatic conformational changes upon host receptor binding. Figure 8.7 illuminates some structural pertur-
334
8 Spike (S) Glycoprotein D614G Mutant
Fig. 8.5 The polar contact LYS417-ASP30 of Chap. 7 between the SARS-CoV-2 spike and the human ACE2 will not be affected by the SARS-CoV-2 S D614G mutation
Fig. 8.6 The secondary structure changes around the residue ASN616 for the Saman Fatihi et al.’s D614G mutant and closed wild-type (replica 1 (WT1) and replica 2 (WT2)) models [114]
bations of the D614G mutant from its wild-type during 200 ns, where T is Turn, E is Extended conformation, B is isolated Bridge, H is .α-Helix, G is .310 -helix, I is .π -helix, and C is Coil. Let us see the MD performances of datasets [75]. By Figs. 8.8 and 8.9, we know the RMSD values for D614G rep1 seem to become stable, but for wild-type rep1, D614G rep2, and wild-type rep2, their RMSD values still intend to go up. Figure 8.10 seems to tell us that the RMSF variations of D614G mutant are less than those of its wild-type. By Table 8.1, we can confirm the conclusion we found in this chapter: the HB GLY614.N-ALA647.O of the D614G mutant becomes stronger than its wild-type, and we find that the D614G mutant has a new strong HB ALA845.NGLY614.O. From Table 8.1, we indeed can confirm D614G mutation made the lost of HBs THR859.OG1-ASP614.OD1/2 [105, 200, 215, 244, 261, 399] because of using 6vsb.pdb to build the models [75, 114]. We should also notice that the
Rep2
Rep1
GLY614.N-ALA647.O 66.18% ALA845.N-GLY614.O 32.35% GLY593.N-GLY614.O 18.63% SER591.OG-GLY614.O 7.35%
Spike D614G mutant GLY614.N-ALA647.O 66.01% LYS854.NZ-GLY614.O 2.96% ALA845.N-GLY614.O 43.84% SER591.OG-GLY614.O 0.99%
SER591.OG-ASP614.O 1.48%, SER591.OG-ASP614.OD2 0.99% THR859.OG1-ASP614.OD2 29.56%, THR859.OG1-ASP614.OD1 23.65% LYS854.NZ-ASP614.OD1 36.45%, LYS854.NZ-ASP614.OD2 24.14%, LYS854.NZ-ASP614.O 0.49% PHE592.N-ASP614.O 1.48% VAL860.N-ASP614.OD1 0.49% GLN613.NE2-ASP614.OD1 1.97% ASP614.N-GLN613.OE1 0.49%
THR859.OG1-ASP614.OD1 55.39%, THR859.OG1-ASP614.OD2 26.47% ARG847.NH2-ASP614.OD2 0.49%, ARG847.NH1-ASP614.O 0.49% GLN613.NE2-ASP614.OD2 0.49% ASP614.N-ALA647.O 24.14%
Spike WT ASP614.N-ALA647.O 44.61% LYS854.NZ-ASP614.O 0.98%, LYS854.NZ-ASP614.OD2 53.43%, LYS854.NZ-ASP614.OD1 19.61%
Table 8.1 The HBs at residue 614 (with occupancy rates) from the analyses of the 200 ns’ MD trajectory data of [75]
8.4 Concluding Remarks 335
336
8 Spike (S) Glycoprotein D614G Mutant
Fig. 8.7 The secondary structure changes around the residue ASN616 for Elio Cino’s 200 ns’ MD simulations rep1 and rep2 of D614G mutant and its wild-type, respectively [75]
8.4 Concluding Remarks
337
RMSD vs Frame: rep1.gro
RMSD vs Frame: rep1.gro
"rep1.gro:(protein) and name CA"
"rep1.gro:(protein) and name CA" 55
30 50
45 25
40
35
20
RMSD (Å)
30
RMSD (Å)
15 25
20
10 15
10 5
5
0
0 0
50
100
150
200
0
50
Frame
100
150
200
Frame
Fig. 8.8 The RMSD graphs of Elio Cino’s 200 ns’ MD simulations rep1 of D614G mutant and its wild-type
RMSD vs Frame: rep2.gro
RMSD vs Frame: rep2.gro 65 "rep2.gro:(protein) and name CA"
"rep2.gro:(protein) and name CA"
35
60
55
30 50
45 25
40
35
20
RMSD (Å)
RMSD (Å) 30
15 25
20 10 15
10 5
5
0
0 0
50
100
Frame
150
200
0
50
100
150
200
Frame
Fig. 8.9 The RMSD graphs of Elio Cino’s 200 ns’ MD simulations rep2 of D614G mutant and its wild-type
Fig. 8.10 The RMSF graphs of Elio Cino’s 200 ns’ MD simulations rep1 of D614G mutant and its wild-type and rep2 of D614G mutant and its wild-type (from up to down in turns), where for each graph, the y-axis (from up to down) is the MD running time from 0 to 200 ns and the x-axis (from left to right) is residue numbers from 27 to 1143
338
8 Spike (S) Glycoprotein D614G Mutant
Fig. 8.11 The SB ASP614.OD1/2-LYS854.NZ of Elio Cino’s 200 ns’ MD simulations rep1 and rep2 (from left to right) of spike wild-type
Fig. 8.12 The RMSF graphs of MD data of 6.5 .μs’ G-up, 8 .μs’ D-up, 6.5 .μs’ G-down, and 8 .μs’ D-down in [229] (from up to down in turns), where for each graph, the y-axis (from up to down) is the MD running time from 0 to 6.5 or 8 .μs and the x-axis (from left to right) is residue numbers from 14 to 1147
mutation made the SBs LYS854.NZ-ASP614.OD1/2 lost (Fig. 8.11), where the labels 0–5 are A:ASP614.OD1-A:LYS854.NZ, A:ASP614.OD2-A:LYS854.NZ, B:ASP614.OD2-B:LYS854.NZ, B:ASP614.OD1-B:LYS854.NZ, C:ASP614.OD2C:LYS854.NZ, and C:ASP614.OD1-C:LYS854.NZ in turns for rep1 and are A:ASP614.OD2-A:LYS854.NZ, A:ASP614.OD1-A:LYS854.NZ, B:ASP614.OD1B:LYS854.NZ, B:ASP614.OD2-B:LYS854.NZ, C:ASP614.OD2-C:LYS854.NZ, and C:ASP614.OD1-C:LYS854.NZ in turns for rep2. Mansbach et al. [229] reported that the SARS-CoV-2 spike variant D614G favors an open conformational state [229] and all their four sets of MD data level off at certain constant RMSD values. We optimized the four (the Mutant G_form-1up model (G-up), the Wild-type D_form-1up model (D-up), the Mutant G_form3down model (G-down), and the Wild-type D_form-3down model (D-down) ) homology models of [229] with RMSD values 2.823235, 2.757211, 2.769470, and 2.852602 Å, respectively, and get all their SBs listed in Tables 8.2 and 8.3, where the four models have 196, 180, 187, and 191 SBs and 559, 563, 543, and 574 HBs, respectively. At residue 614, the D614G mutation made the SB B:ASP614C:LYS854 (D-up and D-down) and the HBs THR859.OG1-ASP614.OD2 (D-up and D-down) and LYS854.NZ-ASP614.OD1 (D-up) of the wild-type lost. The MD data of 8 .μs for wild-type and 6.5 .μs for the variant can confirm our finding: the mutation made the HB GLY614.N-ALA647.O become stronger, GLY614.N-ALA647.O 56.06% (G-up), ASP614.N-ALA647.O 48.15% (D-up), GLY614.N-ALA647.O
8.4 Concluding Remarks
339
Fig. 8.13 The secondary structure changes around the residue ASN616 for MD simulations of D614G mutant G-up and G-down and its wild-type D-up and D-down [229]. Here, A, B, and C denote spike’s A, B, and C chains, respectively
340
8 Spike (S) Glycoprotein D614G Mutant
Fig. 8.14 The secondary structure changes around the residues ASN616 and G/D614 for the optimized G-up, D-up, G-down, and D-down models of [229], where A, B, and C are the three chains of the SARS-CoV-2 spike
58.46% (G-down), and ASP614.N-ALA647.O 56.79% (D-down), where 56.06% > 48.15% and 58.46% .> 56.79%. The MD data can also confirm the lost of SB B:ASP614-C:LYS854 and weak HBs LYS854.NZ-ASP614.OD2 7.41% (D-up), LYS854.NZ-ASP614.OD1 6.17% (D-up), LYS854.NZ-ASP614.OD2 8.64% (Ddown), and LYS854.NZ-ASP614.OD1 3.70% (D-down) by the D614G mutation. By the RMSF variations of the MD (Fig. 8.12), we can confirm the conclusion “the SARS-CoV-2 spike variant D614G favors an open conformational state” of [229]. Figure 8.13 illuminates some structural perturbations of the D614G mutant from its Wild-type during 8 or 6.5 .μs’ MD, where T is Turn, E is Extended conformation, B is isolated Bridge, H is .α-Helix, G is .310 -helix, I is .π -helix, and C is Coil. We can see a slight difference between Figs. 8.13 and 8.7; but we cannot find a rule of the local secondary-structure impact of the D614G mutation from the optimized G-up, D-up, G-down, and D-down models of [229] (Fig. 8.14).
.
D614G-mutant - 1 open (G-up) A:ASP1041-A:LYS1045 B:ASP1041-B:LYS1045 B:ASP1041-C:LYS786 C:ASP1041-C:LYS1045 A:ASP1084-A:LYS1086 A:ASP111-A:LYS113 B:ASP111-B:LYS113 A:ASP1118-C:ARG1091 C:ASP1118-A:ARG1091 C:ASP1118-B:ARG1091 B:ASP138-B:ARG21 B:ASP138-B:ARG78 C:ASP138-C:ARG78 A:ASP178-A:LYS187 B:ASP178-B:LYS182 C:ASP178-C:ARG102 A:ASP198-C:LYS462 B:ASP198-A:ARG357 B:ASP198-A:ARG466 C:ASP198-C:ARG983 A:ASP215-A:ARG214 B:ASP215-B:ARG214 C:ASP215-C:ARG214 A:ASP228-A:LYS202
Wild-type - 1 open (D-up) A:ASP1041-A:LYS1045 B:ASP1041-B:LYS1045 C:ASP1041-C:LYS1045 A:ASP1084-A:HIS1083 A:ASP1084-A:LYS1086 B:ASP1084-B:HIS1083 C:ASP1084-C:HIS1088 B:ASP111-B:LYS113 B:ASP1118-A:ARG1091 A:ASP138-A:LYS77 B:ASP138-B:ARG21 B:ASP138-B:ARG78 C:ASP138-C:ARG78 A:ASP178-A:LYS187 B:ASP198-B:LYS202 A:ASP215-A:ARG214 C:ASP215-C:ARG214 A:ASP228-A:LYS202 B:ASP228-B:LYS202 C:ASP228-C:LYS202 A:ASP253-A:ARG21 A:ASP287-A:LYS278 A:ASP290-A:ARG273 B:ASP290-B:ARG273
Table 8.2 The SBs of the optimized models of [229] D614G-mutant—all down (G-down) A:ASP1041-A:LYS1045 B:ASP1041-B:LYS1045 C:ASP1041-C:LYS1045 A:ASP1084-A:LYS1086 A:ASP111-A:LYS113 C:ASP1118-B:ARG1091 A:ASP138-A:LYS77 B:ASP138-B:ARG78 C:ASP138-C:ARG78 A:ASP178-A:LYS150 B:ASP178-B:ARG190 B:ASP178-B:LYS182 C:ASP178-C:LYS187 A:ASP215-A:ARG214 B:ASP215-B:ARG214 C:ASP215-C:ARG214 A:ASP228-C:ARG357 A:ASP228-A:LYS202 B:ASP228-B:LYS202 B:ASP228-B:LYS41 C:ASP228-C:LYS202 B:ASP253-B:ARG246 A:ASP290-A:ARG273 B:ASP290-B:ARG273
(continued)
Wild-type—all down (D-down) A:ASP1041-A:LYS1045 B:ASP1041-B:LYS1045 C:ASP1041-C:LYS1045 B:ASP1084-B:HIS1088 B:ASP1084-B:LYS1086 A:ASP111-A:LYS113 B:ASP111-B:LYS113 C:ASP111-C:LYS113 A:ASP1118-C:ARG1091 C:ASP1118-B:ARG1091 A:ASP1146-C:LYS1086 A:ASP138-A:LYS77 B:ASP138-B:ARG21 B:ASP138-B:ARG78 C:ASP138-C:ARG21 A:ASP178-A:LYS150 B:ASP178-B:LYS182 C:ASP178-C:LYS182 A:ASP198-A:LYS202 B:ASP198-A:LYS462 A:ASP215-A:ARG214 B:ASP215-B:ARG214 C:ASP215-C:ARG214 A:ASP228-A:LYS202
8.4 Concluding Remarks 341
D614G-mutant - 1 open (G-up) A:ASP228-A:LYS41 B:ASP228-B:LYS202 C:ASP228-C:LYS202 C:ASP228-C:LYS41 A:ASP253-A:ARG21 B:ASP253-B:ARG158 B:ASP287-B:LYS300 A:ASP290-A:ARG273 B:ASP290-B:ARG273 B:ASP290-B:ARG634 C:ASP290-C:ARG634 C:ASP294-C:LYS300 A:ASP389-A:LYS528 B:ASP389-B:LYS528 C:ASP389-C:LYS528 A:ASP398-A:ARG355 B:ASP398-B:ARG355 C:ASP398-C:ARG355 A:ASP40-A:ARG44 B:ASP40-B:ARG44 B:ASP40-B:LYS41 C:ASP40-A:ARG44 C:ASP40-B:ARG567 A:ASP405-A:ARG408 B:ASP405-B:ARG403
Table 8.2 (continued)
Wild-type - 1 open (D-up) B:ASP290-B:ARG634 C:ASP290-C:ARG634 C:ASP294-C:LYS300 C:ASP364-C:LYS528 A:ASP389-A:LYS528 C:ASP389-C:LYS386 B:ASP398-B:ARG355 C:ASP398-C:ARG355 A:ASP40-A:ARG44 B:ASP40-B:HIS49 C:ASP40-C:LYS202 A:ASP405-A:ARG403 A:ASP405-A:LYS417 B:ASP405-B:ARG403 C:ASP405-C:ARG403 A:ASP420-B:LYS386 B:ASP420-B:ARG457 A:ASP427-A:LYS424 B:ASP427-A:ARG408 C:ASP427-C:LYS424 B:ASP428-A:ARG403 B:ASP428-A:LYS417 A:ASP442-A:ARG346 B:ASP442-B:ARG509 C:ASP442-C:ARG509
D614G-mutant—all down (G-down) C:ASP290-C:ARG273 B:ASP294-B:LYS300 C:ASP294-C:LYS300 B:ASP389-B:LYS528 C:ASP389-A:ARG983 A:ASP398-A:ARG355 B:ASP398-B:ARG355 C:ASP398-C:ARG355 A:ASP40-A:ARG44 A:ASP40-A:LYS41 B:ASP40-B:ARG44 C:ASP40-C:ARG44 A:ASP405-A:ARG403 B:ASP405-B:ARG403 C:ASP405-C:ARG408 C:ASP405-C:LYS417 B:ASP420-B:LYS424 C:ASP420-A:LYS386 A:ASP427-A:LYS424 B:ASP427-B:LYS462 C:ASP427-C:LYS424 B:ASP428-B:LYS462 A:ASP442-A:ARG509 B:ASP442-B:ARG509 C:ASP442-C:ARG509
Wild-type—all down (D-down) A:ASP228-A:LYS41 B:ASP228-B:LYS202 B:ASP228-B:LYS41 C:ASP228-C:LYS202 A:ASP253-A:ARG158 B:ASP253-B:ARG246 A:ASP287-A:LYS278 B:ASP287-B:LYS278 A:ASP290-A:ARG273 B:ASP290-B:ARG273 C:ASP290-C:ARG634 A:ASP294-A:LYS300 A:ASP389-A:LYS528 C:ASP389-C:LYS386 A:ASP398-A:ARG355 B:ASP398-B:ARG355 C:ASP398-C:ARG355 A:ASP40-A:ARG44 B:ASP40-B:ARG44 C:ASP40-C:ARG44 A:ASP405-A:ARG408 B:ASP405-B:ARG408 B:ASP405-C:ARG408 C:ASP405-C:ARG403 B:ASP420-B:LYS417
342 8 Spike (S) Glycoprotein D614G Mutant
A:ASP420-A:LYS424 B:ASP420-B:LYS417 C:ASP420-C:LYS424 B:ASP427-B:LYS424 B:ASP428-A:ARG403 B:ASP442-B:ARG509 C:ASP442-C:ARG509 A:ASP467-A:ARG454 A:ASP467-A:ARG457 C:ASP467-C:ARG457 A:ASP53-A:LYS195 B:ASP53-B:LYS195 C:ASP53-C:LYS195 A:ASP568-B:LYS854 B:ASP568-C:LYS854 B:ASP571-C:ARG44 B:ASP571-B:ARG567 B:ASP571-C:HIS49 C:ASP571-C:ARG567 A:ASP574-A:LYS557 A:ASP574-B:LYS854 B:ASP574-B:LYS557 C:ASP574-C:LYS557 C:ASP574-A:LYS854 A:ASP578-A:ARG328 B:ASP578-B:ARG328
A:ASP467-A:ARG466 B:ASP467-B:ARG466 C:ASP467-C:ARG454 C:ASP467-C:ARG457 A:ASP53-A:LYS195 B:ASP53-B:LYS195 C:ASP53-C:LYS195 A:ASP568-B:LYS835 A:ASP568-B:LYS854 C:ASP568-A:LYS835 A:ASP571-B:ARG44 A:ASP571-A:ARG567 B:ASP571-C:ARG44 B:ASP571-C:LYS304 C:ASP571-A:ARG44 A:ASP574-A:LYS557 B:ASP574-B:LYS557 C:ASP574-C:LYS557 C:ASP574-A:LYS835 A:ASP578-A:ARG328 B:ASP578-B:ARG328 C:ASP578-C:ARG328 A:ASP586-A:LYS557 B:ASP586-B:LYS557 C:ASP586-C:LYS557 B:ASP614-C:LYS854
A:ASP467-A:ARG466 C:ASP467-C:ARG454 A:ASP53-A:LYS195 B:ASP53-B:LYS195 C:ASP53-C:LYS195 A:ASP568-B:LYS854 C:ASP568-A:LYS854 A:ASP571-B:ARG44 A:ASP571-A:ARG567 B:ASP571-C:ARG44 B:ASP571-B:ARG567 C:ASP571-A:ARG44 C:ASP571-C:ARG567 :AASP574-A:LYS557 A:ASP574-B:LYS854 B:ASP574-B:LYS557 C:ASP574-A:LYS854 A:ASP578-A:ARG328 B:ASP578-B:ARG328 C:ASP578-C:ARG328 A:ASP586-A:LYS557 B:ASP586-B:LYS557 A:ASP627-A:ARG634 B:ASP627-B:ARG634 C:ASP627-C:ARG634 A:ASP663-A:LYS310 (continued)
A:ASP427-A:LYS424 B:ASP427-B:LYS424 C:ASP427-C:LYS424 A:ASP442-A:ARG509 B:ASP442-B:ARG509 C:ASP442-C:ARG346 C:ASP442-C:ARG509 B:ASP467-C:LYS113 C:ASP467-C:ARG457 A:ASP53-A:LYS195 B:ASP53-B:LYS195 C:ASP53-C:LYS195 A:ASP568-B:LYS835 A:ASP568-B:LYS854 B:ASP568-C:LYS854 A:ASP571-B:ARG44 A:ASP571-A:ARG567 B:ASP571-C:ARG44 B:ASP571-B:ARG567 C:ASP571-A:ARG44 A:ASP574-A:LYS557 A:ASP574-B:LYS835 B:ASP574-C:LYS854 C:ASP574-C:LYS557 A:ASP578-A:ARG328 B:ASP578-B:ARG328
8.4 Concluding Remarks 343
D614G-mutant - 1 open (G-up) C:ASP578-C:ARG328 A:ASP586-A:LYS557 B:ASP586-B:LYS557 C:ASP586-C:LYS557 A:ASP627-A:ARG634 A:ASP663-A:LYS310 B:ASP663-B:LYS310 C:ASP663-C:LYS310 A:ASP737-C:ARG319 A:ASP745-C:ARG319 B:ASP745-A:ARG319 C:ASP745-B:ARG319 A:ASP775-A:LYS733 B:ASP775-B:LYS733 C:ASP775-C:LYS733 C:ASP80-C:ARG78 A:ASP808-A:LYS811 B:ASP808-B:LYS795 C:ASP808-C:LYS811 A:ASP820-A:ARG815 A:ASP820-A:LYS811 B:ASP820-B:ARG815
Table 8.2 (continued)
Wild-type - 1 open (D-up) A:ASP627-A:ARG634 A:ASP663-A:LYS310 B:ASP663-B:LYS310 C:ASP663-C:LYS310 B:ASP737-A:ARG319 A:ASP745-C:ARG319 C:ASP745-B:ARG319 A:ASP775-A:LYS733 B:ASP775-B:LYS733 C:ASP775-C:LYS733 B:ASP80-B:LYS77 C:ASP80-C:ARG78 A:ASP808-A:LYS795 B:ASP808-B:LYS811 C:ASP808-C:LYS795 A:ASP820-A:ARG815 A:ASP820-A:LYS811 B:ASP820-B:ARG815 C:ASP839-C:LYS835 B:ASP843-A:ARG646 C:ASP848-B:ARG646 A:ASP867-A:ARG815
D614G-mutant—all down (G-down) B:ASP663-B:LYS310 C:ASP663-C:LYS310 B:ASP745-A:ARG319 A:ASP775-A:LYS733 B:ASP775-B:LYS733 C:ASP775-C:LYS733 A:ASP796-A:LYS795 A:ASP80-A:LYS77 B:ASP80-B:ARG21 A:ASP808-A:LYS811 B:ASP808-B:LYS811 C:ASP808-C:LYS795 C:ASP808-C:LYS811 A:ASP820-A:ARG815 B:ASP820-B:ARG815 B:ASP820-B:LYS811 C:ASP820-C:ARG815 A:ASP839-A:LYS835 A:ASP843-A:LYS835 B:ASP843-A:ARG646 A:ASP848-C:ARG646 B:ASP848-B:ARG847
Wild-type—all down (D-down) C:ASP578-C:ARG328 A:ASP586-A:LYS557 C:ASP586-C:LYS557 B:ASP614-C:ARG847 A:ASP627-A:ARG634 B:ASP627-B:ARG634 A:ASP663-A:LYS310 B:ASP663-B:LYS310 C:ASP663-C:LYS310 B:ASP745-A:ARG319 C:ASP745-B:ARG319 A:ASP775-A:LYS733 B:ASP775-B:LYS733 C:ASP775-C:LYS733 A:ASP796-A:LYS795 A:ASP80-A:ARG21 A:ASP808-A:LYS811 B:ASP808-B:LYS811 C:ASP808-C:LYS811 A:ASP820-A:ARG815 B:ASP820-B:ARG815 C:ASP820-C:ARG815
344 8 Spike (S) Glycoprotein D614G Mutant
D614G-mutant - 1 open A:ASP830-A:LYS835 A:ASP839-C:ARG646 C:ASP839-B:ARG646 C:ASP839-C:LYS835 B:ASP843-A:ARG646 C:ASP843-B:ARG646 A:ASP848-C:LYS537 C:ASP848-C:ARG847 B:ASP867-B:LYS814 C:ASP867-C:ARG815 A:ASP936-A:LYS933 B:ASP936-B:LYS933 B:ASP950-B:LYS947 C:ASP950-C:LYS947 A:ASP979-A:ARG983 B:ASP979-A:ARG567 C:ASP979-C:ARG983 A:ASP985-C:LYS386 B:ASP985-A:LYS386 A:ASP994-C:ARG995 B:ASP994-A:ARG995 C:ASP994-B:ARG995 A:GLU1017-A:ARG1014 B:GLU1017-B:ARG1014
Wild-type - 1 open C:ASP867-C:ARG847 A:ASP936-A:LYS933 C:ASP936-C:LYS933 A:ASP950-A:LYS947 C:ASP950-C:LYS947 A:ASP979-C:ARG567 A:ASP979-C:HIS519 B:ASP979-B:ARG983 A:ASP985-C:LYS386 A:ASP994-C:ARG995 B:ASP994-A:ARG995 C:ASP994-B:ARG995 A:GLU1017-A:ARG1014 A:GLU1017-B:ARG1019 B:GLU1017-B:ARG1014 B:GLU1017-C:ARG1019 C:GLU1017-A:ARG1019 A:GLU1031-C:ARG1039 B:GLU1031-A:ARG1039 C:GLU1031-B:ARG1039 C:GLU1072-C:LYS1073 B:GLU1144-A:LYS1086 C:GLU1144-B:LYS1086 A:GLU132-A:LYS113
Table 8.3 The SBs of the optimized models of [229] (continuation) D614G-mutant—all down C:ASP848-C:ARG847 A:ASP867-A:ARG847 B:ASP867-B:ARG815 A:ASP88-C:LYS462 A:ASP936-A:LYS933 B:ASP936-B:LYS933 C:ASP950-C:LYS947 A:ASP979-A:ARG983 B:ASP979-B:ARG983 C:ASP979-C:ARG983 A:ASP985-C:LYS386 B:ASP985-A:LYS378 C:ASP985-B:LYS386 A:ASP994-C:ARG995 B:ASP994-A:ARG995 C:ASP994-B:ARG995 A:GLU1017-A:ARG1014 A:GLU1017-A:LYS947 B:GLU1017-B:ARG1014 B:GLU1017-C:ARG1019 C:GLU1017-A:ARG1019 B:GLU1031-A:ARG1039 C:GLU1031-C:ARG1039 C:GLU1072-C:LYS1073
(continued)
Wild-type—all down A:ASP839-A:ARG847 C:ASP839-C:LYS304 C:ASP839-C:LYS964 B:ASP843-B:ARG847 A:ASP867-A:ARG815 B:ASP867-B:ARG815 C:ASP867-C:ARG815 A:ASP936-A:LYS933 A:ASP950-A:LYS947 B:ASP950-B:LYS947 A:ASP979-C:ARG567 A:ASP985-C:LYS386 B:ASP985-A:LYS378 C:ASP985-B:LYS386 A:ASP994-C:ARG995 B:ASP994-A:ARG995 C:ASP994-B:ARG995 A:GLU1017-A:ARG1014 A:GLU1017-B:ARG1019 B:GLU1017-C:ARG1019 C:GLU1017-A:ARG1019 C:GLU1017-C:LYS947 B:GLU1031-A:ARG1039 C:GLU1031-B:ARG1039
8.4 Concluding Remarks 345
D614G-mutant - 1 open C:GLU1017-A:ARG1019 A:GLU1031-C:ARG1039 B:GLU1031-A:ARG1039 C:GLU1031-A:ARG1039 C:GLU1031-C:ARG1039 A:GLU1092-C:ARG1091 C:GLU1092-C:ARG1107 A:GLU1111-C:LYS1086 C:GLU132-C:LYS113 A:GLU154-A:ARG102 B:GLU154-B:ARG102 A:GLU156-A:ARG158 B:GLU156-B:ARG158 B:GLU156-B:ARG246 C:GLU156-C:ARG158 C:GLU156-C:ARG246 A:GLU169-C:ARG357 A:GLU169-A:LYS129 B:GLU169-B:LYS129 C:GLU169-B:ARG357 C:GLU169-C:LYS129 A:GLU180-A:LYS182 C:GLU180-C:LYS182 A:GLU191-A:ARG34 B:GLU191-B:ARG34
Table 8.3 (continued)
Wild-type - 1 open A:GLU154-A:LYS147 B:GLU154-B:ARG102 C:GLU154-C:ARG102 A:GLU156-A:ARG158 B:GLU156-B:ARG158 C:GLU156-C:ARG158 C:GLU156-C:ARG246 A:GLU169-A:LYS129 B:GLU169-B:LYS129 C:GLU169-C:LYS129 B:GLU180-B:LYS187 C:GLU180-C:LYS187 C:GLU180-C:LYS97 A:GLU191-A:ARG34 B:GLU191-B:ARG34 C:GLU191-C:ARG34 A:GLU224-A:LYS206 B:GLU224-B:LYS206 C:GLU224-C:LYS206 C:GLU281-C:LYS278 A:GLU340-A:LYS356 B:GLU406-B:LYS417 C:GLU406-C:ARG403 A:GLU465-A:ARG454 B:GLU465-B:ARG454
D614G-mutant—all down B:GLU1092-B:ARG1107 C:GLU1111-B:LYS1086 B:GLU132-A:ARG466 B:GLU132-B:LYS113 A:GLU156-A:ARG158 A:GLU156-A:ARG246 B:GLU156-B:ARG158 C:GLU156-C:ARG158 C:GLU156-C:ARG246 A:GLU169-A:LYS129 B:GLU169-B:LYS129 C:GLU169-C:LYS129 A:GLU180-A:LYS187 B:GLU180-B:LYS182 C:GLU180-C:LYS147 A:GLU191-A:ARG34 B:GLU191-B:ARG34 C:GLU191-C:ARG34 A:GLU224-A:LYS206 B:GLU224-B:LYS206 C:GLU224-C:LYS206 A:GLU281-C:LYS557 B:GLU281-B:LYS278 C:GLU324-C:LYS537 A:GLU406-A:LYS417
Wild-type—all down C:GLU1031-C:ARG1039 B:GLU1072-B:LYS1073 B:GLU1092-B:ARG1107 B:GLU1111-A:LYS1086 A:GLU154-A:ARG102 B:GLU154-B:ARG102 A:GLU156-A:ARG158 A:GLU169-A:LYS129 B:GLU169-B:LYS129 C:GLU169-C:LYS129 A:GLU180-A:LYS187 A:GLU180-A:LYS97 B:GLU180-B:LYS150 C:GLU180-C:LYS150 A:GLU191-A:ARG34 B:GLU191-B:ARG34 C:GLU191-C:ARG34 A:GLU224-A:LYS206 B:GLU224-B:LYS206 C:GLU224-C:LYS206 C:GLU281-C:LYS278 B:GLU324-B:LYS537 C:GLU324-C:LYS537 A:GLU406-A:ARG403 B:GLU406-B:ARG403
346 8 Spike (S) Glycoprotein D614G Mutant
C:GLU191-C:ARG34 A:GLU224-A:LYS206 B:GLU224-B:LYS206 C:GLU224-C:LYS206 A:GLU281-A:LYS278 B:GLU281-B:LYS835 C:GLU281-C:LYS278 C:GLU298-A:ARG765 C:GLU406-C:ARG403 A:GLU465-A:ARG457 A:GLU465-A:LYS462 C:GLU465-C:ARG457 A:GLU471-A:LYS458 B:GLU471-B:ARG457 C:GLU471-C:LYS458 A:GLU484-B:LYS378 B:GLU484-B:ARG403 B:GLU516-B:ARG355 B:GLU516-B:ARG466 A:GLU554-A:LYS535 B:GLU554-B:LYS535 C:GLU554-C:LYS535 A:GLU583-A:LYS535 B:GLU583-B:LYS535 C:GLU583-C:LYS535 B:GLU619-B:LYS537
C:GLU465-C:ARG457 C:GLU465-C:LYS462 C:GLU471-C:ARG454 A:GLU484-B:LYS378 A:GLU516-A:ARG357 B:GLU516-B:ARG357 C:GLU516-A:LYS41 A:GLU554-A:LYS535 B:GLU554-B:LYS535 C:GLU554-C:LYS535 A:GLU583-A:LYS535 B:GLU583-B:LYS535 C:GLU583-C:LYS535 C:GLU619-C:LYS537 C:GLU661-A:LYS786 A:GLU702-B:LYS790 B:GLU702-C:LYS790 C:GLU702-A:LYS790 A:GLU725-A:HIS1064 A:GLU725-A:LYS1028 B:GLU725-B:HIS1064 B:GLU725-B:LYS1028 C:GLU725-C:HIS1064 C:GLU725-C:LYS1028 B:GLU773-B:ARG1019 C:GLU773-C:ARG1019
B:GLU406-B:LYS417 C:GLU406-C:ARG403 C:GLU406-C:LYS417 A:GLU465-A:ARG457 A:GLU465-A:LYS462 C:GLU465-C:ARG457 A:GLU471-A:ARG454 A:GLU471-A:ARG457 B:GLU471-B:ARG454 B:GLU471-B:ARG457 A:GLU516-B:LYS202 B:GLU516-C:LYS41 A:GLU554-A:LYS535 B:GLU554-B:LYS535 C:GLU554-C:LYS535 A:GLU583-A:LYS558 B:GLU583-:BLYS535 B:GLU619-B:LYS537 C:GLU661-A:LYS786 A:GLU702-B:LYS790 B:GLU702-C:LYS790 C:GLU702-A:LYS790 A:GLU725-A:HIS1064 A:GLU725-A:LYS1028 B:GLU725-B:HIS1064 B:GLU725-B:LYS1028 (continued)
C:GLU406-C:LYS417 A:GLU465-A:ARG457 B:GLU465-B:LYS462 C:GLU465-C:LYS462 A:GLU471-A:LYS458 B:GLU471-B:ARG454 B:GLU471-B:ARG457 C:GLU471-C:LYS458 A:GLU484-A:LYS417 A:GLU516-B:LYS202 A:GLU516-B:LYS41 C:GLU516-A:ARG983 A:GLU554-A:LYS535 B:GLU554-B:LYS535 B:GLU554-B:LYS558 C:GLU554-C:LYS535 A:GLU583-A:LYS535 B:GLU583-B:LYS535 C:GLU583-C:ARG328 A:GLU619-A:LYS537 A:GLU661-B:LYS786 C:GLU661-A:LYS786 A:GLU702-B:LYS790 B:GLU702-C:LYS790 C:GLU702-A:LYS790 A:GLU725-A:HIS1064
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D614G-mutant - 1 open C:GLU619-A:ARG847 C:GLU661-A:LYS786 A:GLU702-B:LYS790 B:GLU702-C:LYS790 C:GLU702-A:LYS790 A:GLU725-A:HIS1064 A:GLU725-A:LYS1028 :GLU725-B:HIS1064 B:GLU725-B:LYS1028 C:GLU725-C:HIS1064 C:GLU725-C:LYS1028 A:GLU773-A:ARG1019 C:GLU773-C:ARG1019 A:GLU780-A:LYS776 B:GLU780-B:ARG1019 B:GLU780-B:LYS776 C:GLU780-C:LYS776 A:GLU868-A:LYS814 B:GLU868-B:LYS814 C:GLU868-C:LYS814 A:GLU96-A:ARG190 B:GLU96-B:ARG190 C:GLU96-C:ARG190 B:GLU988-A:LYS378
Table 8.3 (continued)
Wild-type - 1 open A:GLU780-A:ARG1019 A:GLU780-A:LYS776 C:GLU819-C:ARG815 B:GLU868-A:ARG646 A:GLU96-A:ARG190 B:GLU96-B:ARG190 C:GLU96-C:ARG190 B:GLU988-A:LYS378
D614G-mutant—all down C:GLU725-C:HIS1064 C:GLU725-C:LYS1028 A:GLU773-A:ARG1019 B:GLU773-B:LYS776 C:GLU773-C:ARG1019 A:GLU780-A:LYS776 B:GLU780-B:ARG1019 B:GLU780-B:LYS776 C:GLU780-C:LYS776 A:GLU868-A:ARG847 C:GLU868-C:LYS814 A:GLU96-A:ARG190 B:GLU96-B:ARG190 C:GLU96-C:ARG190 C:GLU990-B:ARG995
Wild-type—all down A:GLU725-A:LYS1028 B:GLU725-B:HIS1064 B:GLU725-B:LYS1028 C:GLU725-C:HIS1064 C:GLU725-C:LYS1028 A:GLU773-A:ARG1019 B:GLU773-B:ARG1019 C:GLU773-C:ARG1019 C:GLU773-C:LYS776 A:GLU780-A:LYS776 B:GLU780-B:LYS776 A:GLU868-A:LYS814 B:GLU868-A:ARG646 B:GLU868-B:LYS814 C:GLU868-C:LYS814 A:GLU96-A:ARG190 B:GLU96-B:ARG190 C:GLU96-C:ARG190 C:GLU990-B:ARG995
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Chapter 9
Spike (S) Glycoprotein N501Y Mutant
Abstract SARS-CoV-2 worldwide pandemic was once attributed to the mutations in the receptor-binding domain (RBD), the area that directly contacts human ACE2; one example is the variant N501Y in the RBD. The structural change may enhance the interaction between the spike protein and the ACE2 receptor of the host, increasing infectivity and increasing binding free energy. The studies of this chapter summarize the following structural bioinformatics for the SARS-CoV-2 N501Y mutant (where D/B chain is human ACE2 and F/E chain is spike RBD): (i). a salt bridge D:ASP39-F:LYS417 is between human ACE2 and spike RBD; (ii). at F:N501Y, there are two hydrogen bonds F:GLN506.NE2-F:TYR501.O and D:LYS353.NZ-F:TYR501.OH, and between ACE2 and RBD, there are hydrogen bonds F:GLN493.NE2-D:GLU44.OE2, D:LYS353.NZ-F:TYR501.OH, F:THR500.OG1-D:TYR50.OH, F:TYR449.OHD:ASP47.OD1, F:TYR489.OH-D:THR36.O, and F:TYR505.OH-D:GLU46.OE2 and E:GLN493.NE2-B:GLU35.OE2, E:GLN493.N/O-B:TYR453.O/N, and E:GLY502.H-B:LYS353.O; (iii). around F/E:N501Y, there are three hydrophobic interactions F:TYR501-D:TYR41, F:TYR501-D:LYS353, and B:LYS353E:GLY504 between spike RBD and human ACE2; (iv). at F:N501Y, there is a .π -.π stacking F:TYR501-D:TYR50 between spike RBD and human ACE2; and (v). the mutation N501Y changes GLY502 and GLN506 from Coil to Turn and changes VAL503-GLY504-TYR505 from .310 -helix to Turn. Keywords Optimized N501Y structures · Structural bioinformatics · Salt bridges · Polar contacts · Hydrophobic contacts and .π -interactions
9.1 Introduction SARS-CoV-2 worldwide pandemic was attributed to the mutations in the receptorbinding domain (RBD), the area that directly contacts human ACE2 [431]. Variant N501Y in the RBD had once emerged in a rapidly spreading lineage (B.1.1.7) in England. This variant is much more contagious than the original version (N501© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_9
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RBD). The structural change may enhance the interaction between the spike protein and the ACE2 receptor of the host, increasing infectivity [438] and increasing binding free energy [132, 174, 431]. It was found that this mutated version of RBD binds to human ACE2 about ten times more tightly than the native version (N501-RBD). This chapter is to optimize currently known N501Y structures and then present the structural bioinformatics such as the noncovalent interactions of hydrogen bonds (HBs), salt bridges (SBs), van der Waals (vdWs) contacts, hydrophobic (HYD) interactions, and .π-interactions (PIs) of the optimized N501Y structures. The performance of these structural bioinformatics is confirmed from some molecular dynamics (MD) simulations known currently. .μ-variant B.1.621 consists of E484K and N501Y mutations, where E484K mutation can help the variant running away from SARS-CoV-2 antibodies. .λ-variant is much like the .μ-variant.
9.2 The Homology Structure of N501Y Mutant Residue 501 is located on the viral RBD surface for cell entry and increases binding to the receptor ACE2. Thus, we had better choose 6m17.pdb. Openly accessible inpcrd and prmtop files of “wat_6m17_N501YboundREDUCED” were downloaded from [25]. From these two files, we generated a pdb file and removed the waters in it, adding TERs; then we input the pdb file into Maestro 10.1 (Academic Use Only) (https://www.schrodinger.com/maestro) to optimize it: “Edit.→Select Atoms.→All” and then “Tools.→Minimize.→Selected Atoms” (backbone RMSD value between the unoptimized and optimized models is 0.596831 Å). We denote the optimized model as the optimized-6m17-N501Y-mutant model in this chapter.
9.3 Structural Bioinformatics of N501Y Mutant 9.3.1 From the optimized-6m17-N501Y-mutant Model The noncovalent interactions of HBs, SBs, vdWs contacts, HYD interactions, and PIs are driving a protein to be able to perform its biological functions. In the below, we will find out the HBs, SBs, HYD interactions, and vdWs contacts of the optimized-6m17-N501Y-mutant model. All the SBs of the optimized-6m17-N501Y-mutant model can be seen in Table 9.1, where SB D:ASP39-F:LYS417 is between human ACE2 and spike RBD and SBs F:ASP405-F:ARG403, F:ASP442-F:ARG509, F:ASP467-F:ARG454, F:ASP467-F:ARG457, F:GLU340-F:LYS356, and F:GLU465-F:ARG457 are still within spike RBD as in Chap. 7.
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Table 9.1 All the SBs of the optimized-6m17-N501Y-mutant model SB D:ASP39-F:LYS417 F:ASP389-F:LYS386 F:ASP405-F:ARG403 F:ASP427-F:LYS424 F:ASP442-F:ARG509 F:ASP467-F:ARG454 F:ASP467-F:ARG457 F:GLU340-F:LYS356 F:GLU465-F:ARG457 F:GLU465-F:LYS462 F:GLU471-F:LYS458 F:GLU516-F:ARG355 D:ASP47-D:LYS353 D:ASP207-D:ARG213 D:ASP210-D:ARG213 D:ASP210-D:ARG228 D:ASP215-D:LYS562 D:ASP335-D:LYS363 D:ASP355-D:ARG357 D:ASP494-D:LYS183 D:ASP499-D:ARG178 D:ASP499-D:LYS481 D:ASP509-D:LYS196 D:ASP597-D:LYS600 D:GLU31-D:LYS35 D:GLU44-D:LYS40 D:GLU46-D:ARG393 D:GLU119-D:LYS123 D:GLU175-D:HIS493 D:GLU190-D:ARG186 D:GLU190-D:LYS470 D:GLU191-D:ARG124 D:GLU198-D:LYS121 D:GLU206-D:ARG213 D:GLU217-D:ARG228 D:GLU236-D:LYS458 D:GLU240-D:LYS243 D:GLU241-D:ARG582 D:GLU310-D:ARG306
In N501Y mutant Human ACE2-spike RBD Within spike RBD Within spike RBD Within spike RBD Within spike RBD Within spike RBD Within spike RBD Within spike RBD Within spike RBD Within spike RBD Within spike RBD Within spike RBD Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2
In wild-type
Yes Yes Yes Yes Yes Yes
Yes Yes
Yes
Yes (continued)
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Table 9.1 (continued) SB D:GLU310-D:LYS313 D:GLU312-D:LYS309 D:GLU375-D:HIS378 D:GLU398-D:ARG514 D:GLU402-D:HIS374 D:GLU406-D:ARG518 D:GLU430-D:LYS419 D:GLU433-D:LYS288 D:GLU435-D:HIS540 D:GLU435-D:LYS541 D:GLU457-D:ARG460 D:GLU467-D:LYS465 D:GLU479-D:LYS475 D:GLU479-D:LYS476 D:GLU483-D:LYS476 D:GLU489-D:ARG482 D:GLU495-D:ARG186 D:GLU536-D:HIS535 D:GLU536-D:LYS416 D:GLU549-D:LYS534 D:GLU571-D:LYS577 D:GLU589-D:ARG582
In N501Y mutant Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2 Within human ACE2
In wild-type Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Yes
Regarding HBs, we find 2 HBs at residue N501Y, F:GLN506.NE2F:TYR501.O and D:LYS353.NZ-F:TYR501.OH (showing that the N501Y mutation enhanced the electrostatic interactions due to the formation of this strong HB; here, there are two HYD interactions at residue N501Y (Fig. 9.1 and Figs. 1C and 1E of [438]): F:TYR501-D:TYR41 (Y501 inserted into a cavity at the binding interface near Y41 of ACE2) and F:TYR501D:LYS353 HYD interactions [217]); 6 HBs between ACE2 and RBD, F:GLN493.NE2-D:GLU44.OE2, D:LYS353.NZ-F:TYR501.OH, F:THR500.OG1D:TYR50.OH, F:TYR449.OH-D:ASP47.OD1, F:TYR489.OH-D:THR36.O, and F:TYR505.OH-D:GLU46.OE2; 70 HBs within F chain spike RBD, F:ALA397.NF:LYS356.O, F:ARG355.NH1-F:SER514.OG, F:ARG355.NH2-F:GLU516.OE2, F:ARG357.NH1-F:ASN394.OD1, F:ARG403.NE-F:ASP405.OD1, F:ARG403. NH1-F:ASP405.OD2, F:ARG454.N-F:ASN422.OD1, F:ARG454.NH2-F:ASP467. O, F:ARG457.NE-F:ASP467.OD2, F:ARG457.NH2-F:GLU465.OE1, F:ARG509. NE-F:SER438.OG, F:ARG509.NH2-F:ASP442.OD2, F:ARG509.N-F:TRP436.O, F:ASN354.ND2-F:SER399.O, F:ASN437.ND2-F:GLN506.OE1, F:ASN439.NF:ASN437.OD1, F:ASN439.ND2-F:PRO499.O, F:ASN448.ND2-F:ASP442.O, F:ASN448.N-F:PHE497.O, F:ASN460.ND2-F:ASP420.OD2, F:ASN487.ND2-
9.3 Structural Bioinformatics of N501Y Mutant
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F:ALA475.O, F:ASP405.OD1-F:ARG403.NE, F:CYS432.N-F:LEU513.O, F:GLN409.N-F:GLU406.O, F:GLN414.NE2-F:GLN414.O, F:GLN493.N-F: TYR453.O, F:GLN506.NE2-F:TYR501.O, F:GLU465.N-F:LYS462.O, F:GLU465. OE2-F:LYS462.NZ, F:GLU471.OE1-F:LYS458.NZ, F:GLU516.OE2-F:ARG355. NH2, F:GLY381.N-F:THR430.O, F:GLY416.N-F:ASP427.OD1, F:GLY416.NF:ASP420.OD1, F:ILE358.N-F:VAL395.O, F:ILE402.N-F:TYR508.O, F:ILE434. N-F:VAL511.O, F:LEU513.N-F:CYS432.O, F:LYS378.N-F:VAL433.O, F:LYS378. NZ-F:TYR380.OH, F:LYS386.NZ-F:ASP389.OD1, F:LYS386.NZ-F:LYS386.O, F:LYS417.N-F:GLN409.OE1, F:LYS417.NZ-F:LEU455.O, F:LYS424.NZF:ASP427.OD2, F:LYS424.NZ-F:LEU425.O, F:LYS444.NZ-F:ASP442.O, F:LYS458.NZ-F:GLU471.OE1, F:LYS462.N-F:GLU465.OE2, F:LYS462.NZF:GLU465.OE2, F:SER373.OG-F:SER371.OG, F:SER375.OG-F:ALA435.O, F:SER443.OG-F:ASN439.OD1, F:SER514.N-F:TYR396.O, F:SER514.OGF:GLU516.OE1, F:THR430.N-F:ASP428.O, F:TRP436.N-F:ARG509.O, F: TYR369.OH-F:THR385.OG1, F:TYR421.N-F:LYS417.O, F:TYR423.N-F:ILE418. O, F:TYR423.OH-F:ASP398.OD2, F:TYR451.OH-F:ASP442.OD1, F:TYR453.NF:GLN493.O, F:TYR473.N-F:TYR489.O, F:TYR495.OH-F:GLU406.OE1, F:TYR508.N-F:ILE402.O, F:VAL433.N-F:LYS378.O, F:VAL510.N-F:PHE400.O, F:VAL511.N-F:ILE434.O, and F:VAL512.N-F:ASP398.O; and 243 HBs within human ACE2.
Fig. 9.1 The N501Y mutation allows two hydrophobic interactions F:TYR501-D:TYR41 and F:TYR501-D:LYS353 between spike RBD and human ACE2 (orange color, hydrophobic; turquoise color, hydrophilic)
For .π -interactions, we find 10 .π -cations, F:TRP353-F:ARG466.NH2+, F: PHE464-F:ARG355.NH2+-F:TYR396, D:TRP57-D:ARG357.NH2+, D:TRP515D:ARG273.NH2+, D:PHE592-D:LYS596.NZ+, D:TYR497-D:LYS183.NZ+, D:TRP174-D:ARG178.NH2+-D:TRP271, and D:TRP478-D:LYS481.NZ+, and 3 .π -.π stackings F:PHE400-F:TYR423-F:TRP353-F:TYR423 within spike RBD, 1 .π -.π stacking F:TYR501-D:TYR50 between spike RBD and human ACE2 (the N501Y mutation allows an aromatic ring-ring interaction .π -.π stacking F:TYR501D:TYR50 and an additional HB F:TYR501.OH-D:LYS353.NZ2 (Fig. 4c of [213]) between the RBD and ACE2 – see Fig. 9.2), and 23 .π -.π stackings within human ACE2.
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Fig. 9.2 The N501Y mutation allows an aromatic ring-ring interaction .π -.π stacking F:TYR501D:TYR50 and an additional HB and vdWs contact F:TYR501.OH-D:LYS353.NZ between spike RBD and human ACE2 (left photo, wild-type; right two photos, N501Y mutant)
The mutation N501Y changes GLY502 and GLN506 from Coil to Turn and changes VAL503-GLY504-TYR505 from .310 -helix to Turn (Fig. 9.3).
Fig. 9.3 N501Y mutation changes GLY502 and GLN506 from Coil to Turn and changes VAL503GLY504-TYR505 from .310 -helix to Turn, where the residue number should minus 236
9.3.2 From MD Simulations The 500 ns’ MD simulation (based on 6M0J.pdb) of [117] showed that “the HB F:TYR501-D:LYS355 is not so pronounced and mainly the hydrophobic and .π -.π stackings of TYR501 increase the binding strength” (Fig. 2B of [117]). The 6 ns’ MD (based on 6M17.pdb) of [14] showed that (i) the N501Y mutation enhanced the electrostatic interactions due to the formation of a strong HB between F:T500 and D:D355 near the mutation site and (ii) SBs F:LYS417-D:ASP30, F:LYS458-D:GLU23, and F:ARG403-D:GLU37 contributed more than 40% of the total binding energies in the wild-type and the mutant. The 200 ns’ MD (based on 6VW1.pdb) of [217] showed that Y501 in the mutated spike RBD can be well-coordinated by Y41 and K353 in human ACE2 through
9.4 Concluding Remarks
355
hydrophobic interactions, which may increase the overall binding affinity of the spike RBD for human ACE2 by approximately 0.81 kcal/mol. The 100 ns’ MD of the N501Y_representative_structure in [431] found that there were also several RBD residues or residue clusters have significantly increased interactions with hACE2 after the N501Y mutation, such as Ser477 and Gln493 and its neighboring residues (Table 2 of [431]). From the optimized N501Y_representative_structure (backbone RMSD value between the unoptimized and optimized structures is 0.003439 Å), we get all the SBs with their HBs of the optimized N501Y_representative_structure listed in Table 9.2; a .π -.π stacking B:TYR41-E:TYR501 at RBD residue TYR501; HBs E:TYR501.NE:GLN498.O,E:GLN506.NE2-E:TYR501.O, and E:TYR501.OH-E:GLY496.O at RBD residue TYR501; HBs E:GLN493.NE2-B:GLU35.OE2, E:GLN493.N/OB:TYR453.O/N, and E:GLY502.H-B:LYS353.O between spike RBD and human ACE2; and a HYD B:LYS353-E:GLY504 between human ACE2 and spike RBD (Fig. 9.4).
Fig. 9.4 The hydrophobic contact B:LYS353-E:GLY504 between human ACE2 and spike RBD of the optimized N501Y_representative_structure
9.4 Concluding Remarks In summary, the studies of this chapter present the following structural bioinformatics for SARS-CoV-2 N501Y mutant (where D/B chain is human ACE2 and F/E chain is spike RBD): (i). a salt bridge D:ASP39-F:LYS417 is between human ACE2 and spike RBD; (ii). at F:N501Y, there are two hydrogen bonds F:GLN506.NE2-F:TYR501.O and D:LYS353.NZ-F:TYR501.OH, and between ACE2 and RBD, there are hydrogen bonds F:GLN493.NE2-D:GLU44.OE2, D:LYS353.NZ-F:TYR501.OH, F:THR500.OG1-D:TYR50.OH, F:TYR449.OHD:ASP47.OD1, F:TYR489.OH-D:THR36.O, and F:TYR505.OH-D:GLU46.OE2 and E:GLN493.NE2-B:GLU35.OE2, E:GLN493.N/O-B:TYR453.O/N, and E:GLY502.H-B:LYS353.O; (iii). around F/E:N501Y, there are three hydrophobic interactions F:TYR501-D:TYR41, F:TYR501-D:LYS353, and B:LYS353E:GLY504 between spike RBD and human ACE2; (iv). at F:N501Y, there is a .π -.π stacking F:TYR501-D:TYR50 between spike RBD and human ACE2; and (v). the mutation N501Y changes GLY502 and GLN506 from Coil to Turn and changes VAL503-GLY504-TYR505 from .310 -helix to Turn.
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9 Spike (S) Glycoprotein N501Y Mutant
Table 9.2 All the SBs with their HBs of the optimized N501Y_representative_structure, where B is human ACE2 SER19-ASP615 and E is spike RBD CYS336-LEU518 SB B:ASP30-E:LYS417 E:ASP398-E:ARG355 E:ASP405-E:ARG403 E:ASP405-E:ARG408 E:ASP420-E:LYS424 E:ASP442-E:ARG509 E:ASP467-E:ARG454 E:ASP467-E:ARG457 E:GLU465-E:ARG466 E:GLU516-E:ARG357 B:GLU23-B:LYS26 B:GLU35-B:LYS31 B:GLU37-B:ARG393 B:GLU140-B:LYS131 B:GLU166-B:HIS493 B:GLU181-B:ARG177 B:GLU181-B:LYS470 B:GLU182-B:ARG115 B:GLU197-B:ARG192 B:GLU208-B:ARG219 B:GLU227-B:LYS458 B:GLU231-B:LYS234 B:GLU310-B:ARG306 B:GLU310-B:LYS313 B:GLU312-B:LYS309 B:GLU398-B:ARG514 B:GLU406-B:ARG518 B:GLU430-B:LYS416 B:GLU430-B:LYS541 B:GLU433-B:LYS288 B:GLU435-B:HIS540 B:GLU435-B:LYS541 B:GLU457-B:ARG460 B:GLU467-B:LYS465 B:GLU479-B:LYS476 B:GLU489-B:ARG482 B:GLU495-B:ARG177 B:GLU495-B:LYS475 B:GLU589-B:ARG582 B:GLU589-B:LYS596
HBs B:ASP30.OD2-E:LYS417.NZ E:ASP398.OD1-E:ARG355.NH1 E:ASP405.OD1-E:ARG403.NH1 E:ARG408.NH1-E:ASP405.OD1 E:ASP420.OD2-E:LYS424.NZ
E:GLU516.OE2-E:ARG357.NH2 B:GLU35.OE2-B:LYS31.NZ B:LYS131.NZ-B:GLU140.OE2 B:HIS493.NE2-B:GLU166.OE2 B:LYS470.NZ-B:GLU181.OE1 B:GLU182.OE1-B:ARG115.NH1, B:GLU182.OE2-B:ARG115.NE B:ARG192.NH1-B:GLU197.OE1, B:ARG192.NE-B:GLU197.OE2 B:GLU208.OE1-B:ARG219.NH1
B:GLU310.N-B:ARG306.O
B:ARG518.NH2-B:GLU406.OE2
B:HIS540.NE2-B:GLU435.OE2, B:GLU435.OE1-B:LYS541.NZ B:GLU435.OE1-B:LYS541.NZ B:LYS465.NZ-B:GLU467.OE2 B:LYS476.NZ-B:GLU479.OE1
(continued)
9.4 Concluding Remarks
357
Table 9.2 (continued) SB B:ASP38-B:LYS353 B:ASP111-B:LYS112 B:ASP198-B:ARG204 B:ASP201-B:ARG204 B:ASP201-B:ARG219 B:ASP216-B:LYS577 B:ASP225-B:HIS228 B:ASP355-B:ARG357 B:ASP335-B:LYS363 B:ASP367-B:LYS441 B:ASP382-B:HIS401 B:ASP431-B:LYS288 B:ASP494-B:LYS174 B:ASP499-B:ARG169 B:ASP499-B:LYS481 B:ASP509-B:LYS187 B:ASP597-B:LYS600
HBs B:LYS112.NZ-B:ASP111.OD2 B:ARG204.NH2-B:ASP198.OD1 B:ASP201.OD1-B:ARG219.NE B:LYS577.NZ-B:ASP216.O B:HIS228.NE2-B:ASP225.OD1 B:LYS363.NZ-B:ASP335.OD2
B:ASP431.OD2-B:LYS288.NZ
Chapter 10
Spike (S) Glycoprotein N165A and N234A Mutant
Abstract Casalino et al. (ACS Cent Sci 6:1722-1734, 2020) revealed an essential structural role of N-glycans at sites N165 and N234 in modulating the conformational dynamics of SARS-CoV-2 spike’s receptor-binding domain (RBD) and showed that deletion of the glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift toward the “down” state. We have not found any structural bioinformatics on salt bridges (SBs) in Casalino et al. (ACS Cent Sci 6:1722-1734, 2020); this chapter presents some SBs of the mutant and its wild-type. Basing on these SBs, we also furthermore studied the structural bioinformatics on hydrogen bonds (HBs) for the mutant and its wild-type. We can confirm the strong SBs GLU1031-ARG1039, ASP442-AEG509, ASP398-ARG355, GLU725-LYS1028, ASP53-LYS195, ASP775-LYS733, and ASP578-ASP328 and can confirm GLU1031-ARG1039, ASP442-AEG509, ASP398-ARG355, and ASP578-ASP328 are strong polar contacts. SBs GLU725-LYS1028, ASP53-LYS195, ASP775-LYS733 (with strong HB A/BS2:LYS733.NZ-A/BS2:ASP775.OD2), and ASP578-ARG328 (replica 6) are always 100% existing within A, B, and C chains, respectively, whether for the mutant or for the wild-type. We also find new strong HBs GLU1031-THR1027 and GLU725-PHE1062 are within each chain. However, we cannot say some differences between the 6vsb-open-N165A-and-N234A-mutant and its wild-type; this might be because the mutations N165A and N234A are changing the polar residue ASN into the strictly hydrophobic residue ALA and residues ASN and ALA are not charged residues. Keywords SARS-CoV-2 N165A and N234A mutant · Open “up” wild-type · Salt bridges analysis · Hydrogen bonds analysis · Comparisons of mutant and wild-type
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_10
359
360
10 Spike (S) Glycoprotein N165A and N234A Mutant
10.1 Introduction The SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. In [55], Casalino et al. [55] revealed an essential structural role of N-glycans at sites N165 and N234 in modulating the conformational dynamics of the spike’s receptorbinding domain (RBD), which is responsible for ACE2 recognition; and the authors showed that deletion of the glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift toward the “down” state. We have not found any structural bioinformatics on salt bridges (SBs) in [55]. This chapter will study the SBs of the mutant, compared with its wild-type, in the open “up” state.
10.2 Materials and Methods See [55] and its supporting information and Amaro Lab COVID-19 Data Sets at amarolab.ucsd.edu/covid19.php. The datasets are six replicas (where three are in 1000 ns and three are in 400 ns) of MD trajectories for full-length spike protein (with glycans) in the open state wild-type and N165A and N234A mutant, respectively. The models were built using the cryo-EM structure 6vsb.pdb as a reference. The spike has four chains: A (16–1273), RBD “UP,” B (16–1273), C (16–1273), and G (1–70); and segment names of ABC chains are AS1 (chain A, 16–685), RBD “UP,” AS2 (chain A, 686–1273), BS1 (chain B, 16–685), BS2 (chain B, 686–1273), CS1 (chain C, 16–685), and CS2 (chain C, 686–1273).
10.3 Results and Discussion Generally, we cannot see great differences of MD secondary structures between the mutant and the wild-type; but we see slight differences of MD secondary structures around the sites of mutations at residues 165 and 234 (Figs. 10.1 and 10.2, where the pink colors are .α-helices and the blue colors are .310 -helices). The MD RMSD performances are illuminated in Fig. 10.3, where the RMSD values are increasing from 0 to 45 Å during 1 .μs and within the last 100 ns the RMSD variations are within 5 Å. The MD RMSF performances are illuminated in Figs. 10.4 and 10.5. In Sect. 7.3.2, the 6VYB-spike-open-model structure and the 6VXX-AchainOptimized structure have SBs ASP820-ARG815, ASP578-ARG328, ASP820LYS811, ASP442-ARG509, ASP467-ARG454, ASP53-LYS195, ASP663LYS310, GLU583-LYS535, ASP775-LYS733, GLU773-ARG1019, GLU773ARG1014, GLU340-LYS356, ASP574-LYS557, ASP574-LYS854, ASP40ARG44, GLU1031-ARG1039, GLU1031-LYS1038, GLU725-LYS1028, ASP1084-
10.3 Results and Discussion
361
Fig. 10.1 The secondary structure changes around the residue 165 for A, B, and C chains (for each chain, the left is for the mutant, and the right is for the wild-type) of the 6vsb-open-N165Aand-N234A-mutant model (T, Turn; E, Extended conformation; B, isolated Bridge; H, .α-Helix; G, .310 -helix; I, .π -helix; C, Coil)
Fig. 10.2 The secondary structure changes around the residue 234 for A, B, and C chains (for each chain, the left is for the mutant, and the right is for the wild-type) of the 6vsb-open-N165Aand-N234A-mutant model (T, Turn; E, Extended conformation; B, isolated Bridge; H, .α-Helix; G, .310 -helix; I, .π -helix; C, Coil)
LYS1086, ASP571-ARG567, ASP405-ARG403, GLU465-ARG457, GLU191ARG34 ASP389-LYS528, ASP398-ARG355, GLU324-LYS537, GLU96-ARG190, and ASP228-LYS202. Our analyses of the MD datasets of [55] can confirm all the above SBs (Tables 10.1 and 10.2, where A, B, and C stand for the three chains
362
10 Spike (S) Glycoprotein N165A and N234A Mutant
Fig. 10.3 The RMSD-time (Å-ns) graphs for the six replicas’ MD data of [55] for the N165A and N234A mutant and the wild-type (the left graph is for the mutant, and the right graph is for the wild-type; series1 to series6 are for replicas 1–6, respectively)
Fig. 10.4 The RMSF graphs for the six replicas’ MD data of [55] for the N165A and N234A mutant and the wild-type (the up six graphs are for the mutant, and the down six graphs are for the wild-type; x-axis (from up to down), 0–100 ns (replicas 1–3) or 0–40 ns (replicas 4–6); y-axis, residue numbers 16–1273)
Fig. 10.5 The RMSF graphs around the mutation sites 165 and 234 for the six replicas’ MD data of [55] for the N165A and N234A mutant and the wild-type (the left six graphs are for the mutant, and the right six graphs are for the wild-type; up, for the mutation site at 165; down, for the mutation site at 234)
of the spike, “A” means the SB is within A chain, and “A-B” means the SB is within neither A chain nor B chain but between A chain and B chain) for both the N165A and N234A mutant and the wild-type. Tables 10.1 and 10.2 tell us that for these SBs, there is no great difference between the mutant and the wild-type; this
10.3 Results and Discussion
363
is because the mutations N165A and N234A are changing the polar residue ASN into the strictly hydrophobic residue ALA, where ASN and ALA are not charged residues. Figure 10.6 illuminates SBs between GLU1031 and ARG1039 of the mutant and the wild-type in the 12 MD replicas; for the mutant, SB GLU1031-ARG1039 is always maintained within A, B, and C, respectively, for all replicas (for replica 4, the mutant is with HBs BS2:ARG1039.NE-BS2:GLU1031.OE2 69.05% and CS2:ARG1039.NE-CS2:GLU1031.OE2 64.29%) and between C chain and B chain for replicas 3 and 6; for the wild-type, SB GLU1031-ARG1039 is always maintained within C chain for replicas 1 and 3–5; for the wild-type MD replica 2, during 0–680 ns, SB GLU1031-ARG1039 is maintained between C chain and B chain, and during 680–1000 ns, SB GLU1031-ARG1039 is maintained within C chain; and for the wild-type MD replica 6, SB GLU1031-ARG1039 is maintained between B chain and A chain and between C chain and B chain. All in all, SB GLU1031-ARG1039 is strongly maintained within or among A, B, and C chains of the spike in CH-CD regions; SB GLU1031-LYS1038 has similar property but is weaker than SB GLU1031-ARG1039. Let us see another two SBs ASP442-ARG509 and ASP398-ARG355 in the receptor-binding domain (RBD, 330–530) of spike. Figure 10.7 tells us SB ASP442ARG509 always exists within A chain and B chain, respectively (where for B chain, mutant replica 4, wild replica 5, and wild replica 3 are without the SB); in Table 10.3, the HBs between ASP442 and ARG509 are very strong. Figure 10.8 tells us SB ASP398-ARG355 always exists within C chain; within A chain, SB ASP398ARG355 always exists for the wild-type, but for the mutant, it is not always existing for MD replica 2 (120–710 ns) and 4 (0–120 ns). In Table 10.3, within C chain furin cleavage site S1 (CS1), the HBs between ASP398 and ARG355 are always strong. SBs GLU725-LYS1028, ASP53-LYS195, ASP775-LYS733 (with strong HB A/BS2:LYS733.NZ-A/BS2:ASP775.OD2 63.41%/62.38%/60.58%), and ASP578ARG328 (replica 6) are always 100% existing within A, B, and C chains, respectively, whether for the mutant or for the wild-type (Figs. 10.9, 10.10, 10.11, and 10.12), where residue LYS1028 is in the central helix (CH, 987–1034) region and ASP53-LYS195 are within the N-terminal domain (NTD, 16–291). Table 10.3 tells us HBs between ASP578 and ARG328 are strong (where ARG328 is in RBD), and we also find new strong HBs GLU1031-THR1027 and GLU725-PHE1062 are within each chain. We list, in Tables 10.4, 10.5, 10.6, and 10.7, all the HBs with more than 60% occupancy rates of the N165A and N234A mutant and its wildtype from the analyses of the 1 .μs’ (replicas 1–3) or 400 ns’ (replicas 4–6) MD trajectories of [55]. Around residues 165 and 234, the mutant has new HBs CS1:ALA163.N-CS1:GLU132.O 60.78% (replica 3), CS1:ALA163.NCS1:GLU132.O 71.43% (replica 6), CS1:VAL130.N-CS1:GLU169.OE2 66.67% (replica 1) (its wild-type has BS1:VAL130.N-BS1:PHE168.O 60.98% (replica 4)), and CS1:TYR396.OH-AS1:PRO230.O 64.36% (replica 1). At residue PHE238, it seems that the mutant has stronger HBs than its wild-type: the mutant has HBs BS1:LEU84.N-BS1:PHE238.O 61.39% (replica 1), BS1:LEU84.N-BS1:PHE238.O
364
10 Spike (S) Glycoprotein N165A and N234A Mutant
69.05% (replica 4), AS1:LEU84.N-AS1:PHE238.O 69.05% (replica 6), and BS1:LEU84.N-BS1:PHE238.O 61.9% (replica 6); but the wild-type only has HB AS1:LEU84.N-AS1:PHE238.O 60.98% (replica 1).
10.4 Concluding Remarks This chapter confirmed the SBs of Sect. 7.3.2 of the SARS-CoV-2 6VYBAchain-Optimized and 6VXX-Achain-Optimized structures. We can confirm the strong SBs GLU1031-ARG1039, ASP442-AEG509, ASP398-ARG355, GLU725LYS1028, ASP53-LYS195, ASP775-LYS733, and ASP578-ASP328 and can confirm GLU1031-ARG1039, ASP442-AEG509, ASP398-ARG355, and ASP578ASP328 are strong polar contacts. SBs GLU725-LYS1028, ASP53-LYS195, ASP775-LYS733 (with strong HB A/BS2:LYS733.NZ-A/BS2:ASP775.OD2), and ASP578-ARG328 (replica 6) are always 100% existing within A, B, and C chains, respectively, whether for the mutant or for the wild-type. We also find new strong HBs GLU1031-THR1027 and GLU725-PHE1062 are within each chain. However, we cannot say some differences between the 6vsb-open-N165A-and-N234A-mutant and its wild-type; this might be because the mutations N165A and N234A are changing the polar residue ASN into the strictly hydrophobic residue ALA and residues ASN and ALA are not charged residues. At last we show the SBs (Tables 10.8 and 10.9) and HBs (Table 10.10) of the 175 ns’ continuous MD trajectory of SARS-CoV-2 glycosylated spike opening [339], where we can confirm our findings above.
Supplementary Information
365
Supplementary Information
Fig. 10.6 The salt bridges between GLU1031 and ARG1039 of the mutant and the wild-type MD replicas 1–6 datasets [55] (left, mutant; right, wild-type; up to down, replica 1 to replica 6)
366
Fig. 10.6 (continued)
10 Spike (S) Glycoprotein N165A and N234A Mutant
Supplementary Information
367
Fig. 10.7 The salt bridges between ASP442 and ARG509 of the mutant and the wild-type MD replicas 1–6 datasets [55] (left, mutant; right, wild-type; up to down, replica 1 to replica 6), where for MD replica 6 within C chain of the wild-type, the SB is ASP442-ARG346 instead of ASP442ARG509
368
Fig. 10.7 (continued)
10 Spike (S) Glycoprotein N165A and N234A Mutant
Supplementary Information Table 10.1 Some SBs of the N165A and N234A mutant and its wild-type from the analyses of the 1 μs’ or 400 ns’ (6 replicas) MD trajectories of [55]
369 SBs
Rep.
SBs of mutant
SBs of wild-type
ASP820-ARG815
1
A, B, C
A, B, C
2
ASP820-LYS811
A, B, C A, B, C
A, B, C
A, B
A, C
5
A, B, C
A, B, C
6
A, B, C
A, B, C
1 2
B
3
A, B
4
B, C
5 6 ASP578-ARG328
ASP442-ARG509
ASP467-ARG454
1
ASP663-LYS310
GLU583-LYS535
GLU773-ARG1019
A, B, C
A, B, C
A, B, C
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
6
A, B, C
A, B, C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
6
A, B, C
A, B
1
B, C
B, C
B, C
B, C
3
A, C
B, C
4
C
B, C
5
B, C
B, C
6
B, C
B, C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
6
A, B, C
A, B, C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
6
A, B
A, B, C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
A, B, C
A, B, C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
6
A, B, C
A, B, C
1
A, B, C
A, B, C
2
B, C
A, B, C
3
A, B, C
A, B, C
4
B
B
5 GLU773-ARG1014
A, B, C
B
2
6 ASP775-LYS733
B A
3
2
ASP53-LYS195
A, B, C
3 4
A, C
A, C
6
A
B
1
B-A
2
B-A
B-A
3
A-C
A-C
4
B-A
5
B-A
A-C, B-A
6
(continued)
370
10 Spike (S) Glycoprotein N165A and N234A Mutant
Table 10.1 (continued)
SBs
Rep.
SBs of mutant
SBs of wild-type
GLU340-LYS356
1
A, B, C
A, B, C
2
ASP574-LYS557
ASP574-LYS854
A, B, C
A, B, C
3
B,C
A, B, C
4
A, B, C
A, C
5
A, B, C
A, B, C
6
B, C
A, B, C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
6
A, B, C
B, C
2
A-B, C-A
C
3
A
4
B-C
5
A-B, C-A
1
6 ASP40-ARG44
Table 10.2 Some SBs of the N165A and N234A mutant and its wild-type from the analyses of the 1 μs’ or 400 ns’ (6 replicas) MD trajectories of [55] (continuation)
C-A, B-C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, C
A, B, C
5
A, B, C
A, B, C
6
A, B, C
A, B, C
SBs
Rep.
SBs of mutant
SBs of wild-type
GLU1031-ARG1039
1
A, B, C, A-B, A-C, B-A, C-B
A, B, C, A-B, A-C, B-A, C-B
2
A, B, C, A-C, B-A, C-B
A, B, C, A-B, A-C, B-A, C-B
3
A, B, C, A-C, B-A, C-B
A, B, C, A-C, B-A, C-B
4
GLU1031-LYS1038
A, B, C, B-A, C-B
A, B, C, A-C
5
A, B, C, A-B, A-C, B-A
A, B, C, A-B, B-A, C-B
6
A, B, C, A-C, B-A, B-C, C-B
A, C, A-C, B-A, C-B A, A-C, B-A
1
A, B-A, C-A
2
A, C-A
3
B
5
A, B-A, C-A A, B-A
4 C, A-C
6 GLU725-LYS1028
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5 ASP1084-LYS1086
ASP571-ARG567
A, B, C
A, B, C
A, B, C
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B
B, C
4
A, B, C
A, C
5
A, B, C
B, C
6
B, C
A, B, C
1
A, B, C
A, B, C
2
A, B, C
B, C
3
A, C
A, B, C
4
ASP405-ARG403
A, B, C
6 1
A, B, C
C
5
A, B, C
B, C
6
A, C
C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, C
5
A, B, C
A, B
6
A, C
B, C
(continued)
Supplementary Information Table 10.2 (continued)
371 SBs
Rep.
SBs of mutant
SBs of wild-type
GLU465-ARG457
1
A, C
B, C
2
B, C
A, C
3
A, C
A, C
4
A
C
5
B
A, C
6
A, C
A, C
1
A, B, C
A, B, C
2
A, B
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
6
A, B, C
A, B, C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
6
B, C
B, C
1
A, B, C
A, B, C
2
A, B, C
A, B, C
3
A, B, C
A, B, C
4
A, B, C
A, B, C
5
A, B, C
A, B, C
6
A, B, C
A, B, C
1
B, C
C
2
A
B, C
3
B, C
A, C
4
A
5
A
A
6
B, C
B, C
1
A
A
2
A
A
3
A
A
4
A
A
5
A
A
GLU191-ARG34
ASP389-LYS528
ASP398-ARG355
GLU324-LYS537
GLU96-ARG190
A
6 ASP228-LYS202
1
A, B
A, B
2
A, B
A, B, C
3
A, B
A, B
4
A, B
A, B
5
A, B
A, B
6
A, B
A, B, C
Wild
Mutant
AS1:TYR451.OH-AS1:ASP442.OD1 64.29% AS1:SER438.OG-AS1:ASP442.OD2 64.29%
BS2:SER1037.OG-BS2:GLU1031.OE2 66.67%
CS2:ARG1039.NE-CS2:GLU1031.OE2 64.29%
AS1:SER438.OG-AS1:ASP442.OD1 60.98%
AS2:GLU1031.N-AS2:THR1027.O 60.98%
AS1:PHE347.N-AS1:ASP442.OD2 60.98%
AS1:ARG509.NE-AS1:ASP442.OD1 75.61% BS1:ARG509.NH2-BS1:ASP442.OD1 63.41%
BS2:GLU1031.N-BS2:THR1027.O 68.29%
Rep6
BS1:ARG509.NH2-BS1:ASP442.OD2 65.85% AS1:ARG509.NE-AS1:ASP442.OD1 60.98%
CS2:GLU1031.N-CS2:THR1027.O 73.17%
CS2:SER1037.OG-CS2:GLU1031.OE1 60.98%
Rep5
BS1:ARG509.NH1-BS1:ASP442.OD1 78.05% AS1:ARG509.NE-AS1:ASP442.OD1 75.61% AS1:TYR451.OH-AS1:ASP442.OD2 65.85%
AS2:GLU1031.N-AS2:THR1027.O 64.36%
BS2:GLU1031.N-BS2:THR1027.O 70.73%
CS2:GLU1031.N-CS2:THR1027.O 63.41%
Rep3
Rep4
AS2:GLU1031.N-AS2:THR1027.O 61.39%
AS1:ARG509.NH2-AS1:ASP442.OD2 68.32% AS1:ARG509.NE-AS1:ASP442.OD1 62.38%
CS2:GLU1031.N-CS2:THR1027.O 64.36%
BS2:GLU1031.N-BS2:THR1027.O 62.38%
Rep2
BS1:ASN354.N-BS1:ASP398.OD2 68.29%
CS1:TYR423.OH-CS1:ASP398.OD2 68.29%
CS1:ARG355.NE-CS1:ASP398.OD1 85.37%
CS1:ARG355.NE-CS1:ASP398.OD2 60.98%
BS1:VAL512.N-BS1:ASP398.O 63.41%
AS1:VAL512.N-AS1:ASP398.O 65.85%
AS1:VAL512.N-AS1:ASP398.O 61.39%
BS1:VAL512.N-BS1:ASP398.O 63.37%
CS1:ARG355.NH2-CS1:ASP398.OD2 67.33%
CS1:ARG355.NE-CS1:ASP398.OD1 86.14%
CS1:ASP398.N-CS1:VAL512.O 60.4%
AS1:TYR451.OH-AS1:ASP442.OD1 66.34% AS1:ARG509.NE-AS1:ASP442.OD2 63.37%
BS1:VAL512.N-BS1:ASP398.O 66.34%
AS1:VAL512.N-AS1:ASP398.O 69.05%
AS1:VAL512.N-AS1:ASP398.O 70.73%
CS1:TYR423.OH-CS1:ASP398.OD2 73.17%
CS1:ARG355.NE-CS1:ASP398.OD1 75.61%
CS1:ARG355.NE-CS1:ASP398.OD1 61.9%
CS1:ASP398.N-CS1:VAL512.O 61.9%
BS1:VAL512.N-BS1:ASP398.O 64.29%
AS1:VAL512.N-AS1:ASP398.O 61.76%
AS1:SER438.OG-AS1:ASP442.OD2 71.29%
CS2:GLU1031.N-CS2:THR1027.O 66.67%
CS2:GLU1031.N-CS2:THR1027.O 61.39%
Rep6
Rep1
AS2:GLU1031.N-AS2:THR1027.O 82.93%
AS2:GLU1031.N-AS2:THR1027.O 61.9%
CS2:GLU1031.N-CS2:THR1027.O 64.29%
AS1:ARG509.NE-AS1:ASP442.OD2 80.95%
BS2:ARG1039.NE-BS2:GLU1031.OE2 69.05%
Rep5
Rep4
BS1:ARG509.NE-BS1:ASP442.OD2 66.67% BS1:ARG509.NH2-BS1:ASP442.OD1 61.76%
CS2:GLU1031.N-CS2:THR1027.O 68.63%
BS2:GLU1031.N-BS2:THR1027.O 63.73%
Rep3
CS1:ASP442.N-CS1:SER438.O 62.38%
CS1:ARG355.NH2-CS1:ASP398.OD2 61.39% AS1:VAL512.N-AS1:ASP398.O 61.39%
AS1:SER438.OG-AS1:ASP442.OD2 74.26%
AS2:GLU1031.N-AS2:THR1027.O 71.15%
ASP398-ARG355 CS1:ARG355.NE-CS1:ASP398.OD1 79.21%
AS1:ARG509.NH2-AS1:ASP442.OD1 65.35%
Rep2
ASP442-ARG509 AS1:ARG509.NE-AS1:ASP442.OD2 77.23%
BS2:GLU1031.N-BS2:THR1027.O 61.39%
Rep1
GLU1031-ARG1039
Table 10.3 The HBs of 7 strong SBs of the N165A and N234A mutant and its wild-type from the analyses of the 1 μs’ or 400 ns’ (6 replicas) MD trajectories of [55]
372 10 Spike (S) Glycoprotein N165A and N234A Mutant
Wild
Mutant
BS2:PHE1062.N-BS2:GLU725.O 60.78%
Rep3
Rep2
Rep6
Rep5
Rep4
Rep3
ASP578-ARG328
BS2:PHE1062.N-BS2:GLU725.O 70.73%
BS1:ARG328.NE-BS1:ASP578.OD1 60.98%
CS1:ASP578.N-CS1:GLU583.O 63.41%
CS1:ARG328.NH1-CS1:ASP578.OD2 70.73%
CS1:THR581.OG1-CS1:ASP578.OD1 85.37%
AS1:ASP578.N-AS1:GLU583.O 63.37%
AS1:ARG328.NE-AS1:ASP578.OD2 65.35%
BS1:ASP578.N-BS1:GLU583.O 60.4%
CS1:ASP578.N-CS1:GLU583.O 61.39%
AS1:ASP578.N-AS1:GLU583.O 63.37%
AS1:ASP578.N-AS1:GLU583.O 60.98%
CS1:ASP578.N-CS1:GLU583.O 68.29%
AS1:ASP578.N-AS1:GLU583.O 61.54%
CS1:ARG328.NH2-CS1:ASP578.OD2 64.36%
CS1:THR581.OG1-CS1:ASP578.OD2 74.26%
CS1:ARG328.NE-CS1:ASP578.OD1 76.24%
CS1:ARG328.NH2-CS1:ASP578.OD1 75.61%
AS2:LYS733.NZ-AS2:ASP775.OD2 63.41%
BS2:LYS733.NZ-BS2:ASP775.OD2 62.38%
BS2:LYS733.NZ-BS2:ASP775.OD2 60.58%
ASP775-LYS733
BS2:PHE1062.N-BS2:GLU725.O 73.17%
AS1:ARG273.N-AS1:ASP53.O 60.98%
CS1:ARG273.N-CS1:ASP53.O 60.98%
ASP53-LYS195
CS2:PHE1062.N-CS2:GLU725.O 68.29%
BS2:PHE1062.N-BS2:GLU725.O 60.4%
BS2:PHE1062.N-BS2:GLU725.O 66.67%
Rep6
Rep1
AS2:PHE1062.N-AS2:GLU725.O 65.85%
Rep5
Rep4
AS2:PHE1062.N-AS2:GLU725.O 75%
Rep2
GLU725-LYS1028
CS2:PHE1062.N-CS2:GLU725.O 63.37%
Rep1
Supplementary Information 373
374
10 Spike (S) Glycoprotein N165A and N234A Mutant
Fig. 10.8 The salt bridges between ASP398 and ARG355 of the mutant and the wild-type MD replicas 1–6 datasets [55] (left, mutant; right, wild-type; up to down, replica 1 to replica 6)
Supplementary Information
Fig. 10.8 (continued)
375
376
10 Spike (S) Glycoprotein N165A and N234A Mutant
Fig. 10.9 The salt bridges between GLU725 and LYS1028 of the mutant and the wild-type MD replicas 1–6 datasets [55] (left, mutant; right, wild-type; up to down, replica 1 to replica 6)
Supplementary Information
Fig. 10.9 (continued)
377
378
10 Spike (S) Glycoprotein N165A and N234A Mutant
Fig. 10.10 The salt bridges between ASP53 and LYS195 of the mutant and the wild-type MD replicas 1–6 datasets [55] (left, mutant; right, wild-type; up to down, replica 1 to replica 6)
Supplementary Information
Fig. 10.10 (continued)
379
380
10 Spike (S) Glycoprotein N165A and N234A Mutant
Fig. 10.11 The salt bridges between ASP775 and LYS733 of the mutant and the wild-type MD replicas 1–6 datasets [55] (left, mutant; right, wild-type; up to down, replica 1 to replica 6)
Supplementary Information
381
Fig. 10.11 (continued)
Fig. 10.12 The salt bridges between ASP578 and ARG328 of the mutant and the wild-type MD replica 6 datasets [55] (left, mutant; right, wild-type)
382
10 Spike (S) Glycoprotein N165A and N234A Mutant
Table 10.4 The HBs with more than 60% occupancy rates of the N165A and N234A mutant from the analyses of the 1 μs’ (replicas 1–3) MD trajectories of [55] Replica 1
Replica 2
Replica 3
CS1:ARG355.NE-CS1:ASP398.OD1 79.21%
AS1:LEU585.N-AS1:VAL576.O 79.81%
BS1:ARG457.N-BS1:ASP420.OD1 77.45%
CS1:LEU585.N-CS1:VAL576.O 78.22%
BS1:TYR91.N-BS1:GLY268.O 76.92%
CS2:SER1051.OG-CS2:HSE1064.ND1 76.47%
AS1:ARG509.NE-AS1:ASP442.OD2 77.23%
AS1:ARG683.NH1-AS2:ASP950.OD1 76.92%
CS1:TYR91.N-CS1:GLY268.O 74.51%
BS1:VAL511.N-BS1:ILE434.O 77.23%
AS2:PHE1062.N-AS2:GLU725.O 75%
AS1:VAL511.N-AS1:ILE434.O 74.51%
CS1:ARG328.NE-CS1:ASP578.OD1 76.24%
AS1:LEU277.N-AS1:HSE49.O 74.04%
BS1:PHE106.N-BS1:LEU117.O 74.51%
AS1:LEU118.N-AS1:LYS129.O 75.25%
BS1:VAL511.N-BS1:ILE434.O 73.08%
BS1:PHE43.N-AS1:PHE565.O 73.53%
CS1:LEU277.N-CS1:HSE49.O 74.26%
CS1:TYR380.N-CS1:GLY431.O 72.12%
AS1:LEU585.N-AS1:VAL576.O 73.53%
CS1:THR581.OG1-CS1:ASP578.OD2 74.26%
AS1:ARG34.NE-AS1:GLU191.OE1 72.12%
BS1:VAL511.N-BS1:ILE434.O 72.55%
AS1:SER438.OG-AS1:ASP442.OD2 74.26%
CS2:CYS1082.N-CS2:VAL1133.O 71.15%
BS1:ILE598.N-BS1:ALA609.O 71.57%
BS1:LEU118.N-BS1:LYS129.O 73.27%
AS2:GLU1031.N-AS2:THR1027.O 71.15%
BS1:LEU118.N-BS1:LYS129.O 70.59%
BS1:PHE43.N-AS1:PHE565.O 73.27%
AS1:TYR91.OH-AS1:GLU191.OE1 71.15%
AS1:LEU611.N-AS1:SER596.O 70.59%
BS1:ILE598.N-BS1:ALA609.O 72.28%
CS1:ILE598.N-CS1:ALA609.O 71.15%
BS2:TYR695.OH-BS1:GLU661.O 69.61%
AS1:LEU611.N-AS1:SER596.O 72.28%
AS2:MET902.N-AS2:PHE898.O 70.19%
AS1:TYR91.N-AS1:GLY268.O 69.61%
BS1:TYR91.N-BS1:GLY268.O 72.28%
CS2:THR1066.N-CS2:SER721.O 70.19%
BS1:TYR508.N-BS1:ILE402.O 69.61%
AS1:TYR91.N-AS1:GLY268.O 72.28%
AS1:TYR91.N-AS1:GLY268.O 70.19%
CS1:ILE598.N-CS1:ALA609.O 69.61%
AS2:SER1051.OG-AS2:HSE1064.ND1 72.28%
BS1:TRP64.N-BS1:ALA27.O 70.19%
CS2:THR1066.OG1-CS2:LYS1045.O 68.63%
AS2:ASN928.N-AS2:ALA924.O 71.29%
CS2:THR1066.OG1-CS2:LYS1045.O 69.23%
BS1:TYR266.N-BS1:ALA93.O 68.63%
AS1:LEU277.N-AS1:HSE49.O 70.3%
BS1:LEU118.N-BS1:LYS129.O 68.27%
CS2:GLU1031.N-CS2:THR1027.O 68.63%
BS1:TYR266.N-BS1:ALA93.O 70.3%
AS1:LEU611.N-AS1:SER596.O 67.31%
BS1:ARG454.N-BS1:ASN422.OD1 67.65%
AS1:LEU585.N-AS1:VAL576.O 70.3%
BS1:CYS336.N-BS1:VAL362.O 67.31%
BS1:LEU611.N-BS1:SER596.O 67.65%
BS1:VAL551.N-BS1:THR588.O 70.3%
AS1:LEU118.N-AS1:LYS129.O 67.31%
AS1:LEU277.N-AS1:HSE49.O 67.65%
CS2:SER1051.OG-CS2:HSE1064.ND1 69.31%
AS1:VAL511.N-AS1:ILE434.O 67.31%
AS1:GLN271.N-AS1:PHE55.O 67.65%
AS1:THR323.N-AS1:CYS538.O 69.31%
BS2:THR1077.OG1-BS2:PHE1095.O 66.35%
AS2:ASN928.N-AS2:ALA924.O 66.67%
AS1:PHE106.N-AS1:LEU117.O 69.31%
CS2:ASN928.N-CS2:ALA924.O 66.35%
CS1:LEU277.N-CS1:HSE49.O 66.67%
BS1:ILE434.N-BS1:VAL511.O 69.31%
BS2:THR883.OG1-BS2:ALA879.O 66.35%
BS2:THR1066.OG1-BS2:LYS1045.O 66.67%
BS2:SER1051.OG-BS2:HSE1064.ND1 68.32%
AS1:ILE598.N-AS1:ALA609.O 66.35%
BS1:ARG509.NE-BS1:ASP442.OD2 66.67%
BS1:ILE651.N-BS1:VAL610.O 68.32%
AS1:TYR37.OH-AS1:LEU54.O 66.35%
AS1:PHE543.N-AS1:LEU546.O 66.67%
CS1:TYR91.OH-CS1:GLU191.OE2 68.32%
BS1:ILE358.N-BS1:VAL395.O 66.35%
AS1:PHE106.N-AS1:LEU117.O 66.67%
AS2:LEU1063.N-AS2:PHE1052.O 68.32%
CS1:CYS671.N-CS2:TYR695.O 66.35%
CS1:TRP64.N-CS1:ALA27.O 66.67%
AS2:ALA879.N-AS2:SER875.O 67.33%
BS1:ILE598.N-BS1:ALA609.O 65.38%
CS2:CYS1082.N-CS2:VAL1133.O 65.69%
AS1:ILE587.N-AS1:ASP574.O 67.33%
CS1:LEU611.N-CS1:SER596.O 65.38%
CS2:ASN928.N-CS2:ALA924.O 65.69%
CS1:VAL511.N-CS1:ILE434.O 67.33%
AS2:ARG1019.NH1-AS2:ASN777.OD1 65.38%
BS2:GLN1054.N-BS2:VAL1061.O 65.69%
AS2:THR1066.OG1-AS2:LYS1045.O 66.34%
CS1:PHE275.N-CS1:THR51.O 65.38%
AS1:LEU650.N-AS1:PHE643.O 65.69%
BS1:TYR612.N-BS1:CYS649.O 66.34%
CS2:PHE1089.N-CS2:PHE1121.O 64.42%
BS1:VAL127.N-BS1:VAL120.O 65.69%
CS1:ILE587.N-CS1:ASP574.O 66.34%
BS1:PHE106.N-BS1:LEU117.O 64.42%
BS1:TYR37.OH-BS1:LEU54.O 65.69%
AS2:VAL1008.N-AS2:LEU1004.O 66.34%
CS1:VAL62.N-CS1:THR29.O 64.42%
AS1:TYR313.N-AS1:VAL597.O 65.69%
CS1:SER94.OG-CS1:ALA264.O 66.34%
BS2:THR1066.OG1-BS2:LYS1045.O 64.42%
BS2:ASN777.N-BS2:GLU773.O 64.71%
BS1:ARG44.NH2-BS1:ASP40.OD1 66.34%
AS1:ARG683.NH2-AS2:ASP950.OD2 64.42%
BS1:VAL551.N-BS1:THR588.O 64.71%
BS2:THR1077.OG1-BS2:PHE1095.O 65.35%
BS2:ASN777.N-BS2:GLU773.O 63.46%
CS1:TYR508.N-CS1:ILE402.O 64.71%
CS1:ILE128.N-CS1:TYR170.O 65.35%
CS1:LEU277.N-CS1:HSE49.O 63.46%
BS1:LEU585.N-BS1:VAL576.O 64.71%
CS1:LEU513.N-CS1:CYS432.O 65.35%
AS1:LYS202.N-AS1:LYS195.O 63.46%
AS1:LEU118.N-AS1:LYS129.O 64.71%
AS1:ARG509.NH2-AS1:ASP442.OD1 65.35%
AS1:PHE106.N-AS1:LEU117.O 63.46%
BS2:GLU1031.N-BS2:THR1027.O 63.73%
BS1:TYR380.N-BS1:GLY431.O 65.35%
AS2:SER1051.OG-AS2:HSE1064.ND1 62.5%
BS1:TYR313.OH-BS1:GLU309.O 63.73%
BS2:ALA879.N-BS2:SER875.O 64.36%
AS2:PHE1052.N-AS2:LEU1063.O 62.5%
BS1:TYR91.N-BS1:GLY268.O 63.73%
AS1:TYR612.N-AS1:CYS649.O 64.36%
AS2:ASN777.N-AS2:GLU773.O 62.5%
CS2:THR883.OG1-CS2:ALA879.O 63.73%
AS1:LEU229.N-AS1:PHE201.O 64.36%
AS2:HSD1088.N-AS2:ILE1081.O 62.5%
BS2:SER1051.OG-BS2:HSE1064.ND1 63.73%
AS2:TYR695.N-AS1:CYS671.O 64.36%
BS1:PHE194.N-BS1:VAL90.O 62.5%
BS1:ILE587.N-BS1:ASP574.O 63.73%
AS1:TYR37.OH-AS1:LEU54.O 64.36%
BS2:LEU1218.N-BS2:TRP1214.O 62.5%
BS1:CYS336.N-BS1:VAL362.O 63.73%
CS1:ARG328.NH2-CS1:ASP578.OD2 64.36%
CS2:ASN777.N-CS2:GLU773.O 62.5%
BS2:VAL1061.N-BS2:GLN1054.O 62.75%
AS1:ILE598.N-AS1:ALA609.O 64.36%
CS2:ARG1019.NH1-CS2:ASN777.OD1 62.5%
CS1:TYR37.OH-CS1:LEU54.O 62.75%
AS1:VAL433.N-AS1:LYS378.O 64.36%
AS2:THR1077.OG1-AS2:PHE1095.O 62.5%
BS2:THR1066.N-BS2:SER721.O 62.75%
CS1:TYR396.OH-AS1:PRO230.O 64.36%
CS2:THR883.OG1-CS2:ALA879.O 61.54%
AS2:THR1066.OG1-AS2:LYS1045.O 62.75%
BS2:THR1066.OG1-BS2:LYS1045.O 63.37%
BS1:TYR313.N-BS1:VAL597.O 61.54%
BS1:TYR612.N-BS1:CYS649.O 62.75%
CS2:PHE1062.N-CS2:GLU725.O 63.37%
BS1:LEU611.N-BS1:SER596.O 61.54%
BS1:ASN460.N-BS1:ASP420.OD2 62.75%
BS2:TYR695.OH-BS1:GLU661.O 63.37%
BS1:LEU585.N-BS1:VAL576.O 61.54%
BS2:VAL1096.N-BS2:PHE1103.O 62.75%
BS1:LEU650.N-BS1:PHE643.O 63.37%
BS1:TYR380.N-BS1:GLY431.O 61.54%
CS1:ARG44.NH2-CS1:ASP40.OD2 62.75%
BS1:LEU223.N-BS1:VAL36.O 63.37%
BS1:VAL127.N-BS1:VAL120.O 61.54%
BS1:LEU223.N-BS1:VAL36.O 62.75%
BS1:LEU585.N-BS1:VAL576.O 62.38%
CS1:VAL511.N-CS1:ILE434.O 61.54%
CS1:TYR380.N-CS1:GLY431.O 62.75%
BS1:TYR37.OH-BS1:LEU54.O 62.38%
AS1:TYR266.N-AS1:ALA93.O 61.54%
BS1:ARG44.NH2-BS1:ASP40.OD2 62.75%
BS1:VAL127.N-BS1:VAL120.O 62.38%
AS1:CYS336.N-AS1:VAL362.O 61.54%
AS1:LYS202.N-AS1:LYS195.O 61.76%
AS2:THR1077.OG1-AS2:PHE1095.O 62.38%
CS2:TYR1067.N-CS2:TYR1047.O 61.54%
BS1:ARG509.NH2-BS1:ASP442.OD1 61.76%
(continued)
Supplementary Information
383
Table 10.4 (continued) Replica 1
Replica 2
Replica 3
BS1:TYR313.OH-BS1:GLU309.O 62.38%
AS1:ASP578.N-AS1:GLU583.O 61.54%
AS1:VAL512.N-AS1:ASP398.O 61.76%
CS1:ASP442.N-CS1:SER438.O 62.38%
AS2:THR1066.OG1-AS2:LYS1045.O 60.58%
BS2:PHE1075.N-BS2:ILE712.O 61.76%
BS2:GLU1031.N-BS2:THR1027.O 61.39%
CS2:SER1051.OG-CS2:HSE1064.ND1 60.58%
AS1:VAL127.N-AS1:VAL120.O 61.76%
BS2:ASN777.N-BS2:GLU773.O 61.39%
BS2:LYS733.NZ-BS2:ASP775.OD2 60.58%
AS1:ILE598.N-AS1:ALA609.O 61.76%
AS1:PHE543.N-AS1:LEU546.O 61.39%
AS1:PHE275.N-AS1:THR51.O 60.58%
CS1:VAL551.N-CS1:THR588.O 61.76%
CS1:TYR91.N-CS1:GLY268.O 61.39%
CS1:TYR91.N-CS1:GLY268.O 60.58%
CS2:HSD1088.N-CS2:ILE1081.O 60.78%
BS1:LEU84.N-BS1:PHE238.O 61.39%
BS1:LYS202.N-BS1:LYS195.O 60.58%
BS2:PHE1062.N-BS2:GLU725.O 60.78%
CS1:ARG355.NH2-CS1:ASP398.OD2 61.39%
BS2:ILE742.N-BS2:CYS738.O 60.58%
CS1:PHE275.N-CS1:THR51.O 60.78%
BS2:THR1231.OG1-BS2:ILE1227.O 61.39%
CS1:GLN271.N-CS1:PHE55.O 60.58%
BS1:LEU117.N-BS1:PHE106.O 60.78%
CS2:THR1077.OG1-CS2:PHE1095.O 61.39%
CS1:VAL362.N-CS1:ASN334.O 60.58%
BS1:TYR396.N-BS1:SER514.O 60.78%
BS2:ASN928.N-BS2:ALA924.O 61.39%
CS2:VAL1096.N-CS2:PHE1103.O 60.58%
AS1:ILE434.N-AS1:VAL511.O 60.78%
BS1:ILE587.N-BS1:ASP574.O 61.39%
AS1:LEU189.N-AS1:THR208.O 60.58%
CS1:ALA163.N-CS1:GLU132.O 60.78%
AS1:VAL512.N-AS1:ASP398.O 61.39% CS1:LEU611.N-CS1:SER596.O 60.4% BS1:VAL362.N-BS1:ASN334.O 60.4% AS1:VAL511.N-AS1:ILE434.O 60.4% BS1:LEU277.N-BS1:HSE49.O 60.4% AS1:PHE92.N-AS1:PHE192.O 60.4% BS1:TYR396.N-BS1:SER514.O 60.4% BS1:PHE275.N-BS1:THR51.O 60.4%
Table 10.5 The HBs with more than 60% occupancy rates of the N165A and N234A mutant from the analyses of the 400 ns’ (replicas 4–6) MD trajectories of [55] Replica 4
Replica 5
Replica 6
AS1:LEU650.N-AS1:PHE643.O 85.71%
CS1:TYR91.N-CS1:GLY268.O 90.24%
CS1:ARG646.NE-CS1:ASP614.OD1 85.71%
CS1:TYR38.OH-CS1:GLY283.O 85.71%
AS2:GLU1031.N-AS2:THR1027.O 82.93%
BS1:LEU611.N-BS1:SER596.O 80.95%
BS1:LEU585.N-BS1:VAL576.O 83.33%
AS1:ARG683.NH1-AS2:ASP950.OD1 82.93%
AS1:TYR313.OH-AS1:GLU309.O 78.57%
CS1:TYR91.OH-CS1:GLU191.OE1 80.95%
BS2:THR1077.OG1-BS2:PHE1095.O 82.93%
AS1:ARG44.NH2-AS1:ASP40.OD1 78.57%
AS1:ARG34.NE-AS1:GLU191.OE1 80.95%
AS1:LEU277.N-AS1:HSE49.O 80.49%
AS1:ARG357.NH2-AS1:GLU516.OE1 78.57%
AS1:ARG509.NE-AS1:ASP442.OD2 80.95%
CS1:ILE434.N-CS1:VAL511.O 80.49%
CS2:SER1051.OG-CS2:HSE1064.ND1 76.19%
AS1:ARG683.NH2-AS2:ASP950.OD2 80.95%
AS1:PHE106.N-AS1:LEU117.O 78.05%
BS2:THR1066.OG1-BS2:LYS1045.O 76.19%
BS1:TYR91.N-BS1:GLY268.O 78.57%
AS1:LEU611.N-AS1:SER596.O 75.61%
BS1:LEU118.N-BS1:LYS129.O 76.19%
AS1:VAL511.N-AS1:ILE434.O 78.57%
CS1:ARG355.NE-CS1:ASP398.OD1 75.61%
AS1:LEU650.N-AS1:PHE643.O 73.81%
AS1:LEU277.N-AS1:HSE49.O 78.57%
CS1:TRP64.N-CS1:ALA27.O 75.61%
AS1:ILE598.N-AS1:ALA609.O 73.81%
AS2:THR887.OG1-AS2:SER884.O 76.19%
CS1:TYR380.N-CS1:GLY431.O 75.61%
AS1:TYR91.N-AS1:GLY268.O 73.81%
AS1:ARG683.NH1-AS2:ASP950.OD1 76.19%
CS2:THR1077.OG1-CS2:PHE1095.O 73.17%
BS1:PHE43.N-AS1:PHE565.O 73.81%
BS1:LEU611.N-BS1:SER596.O 76.19%
BS1:LEU585.N-BS1:VAL576.O 73.17%
AS1:VAL127.N-AS1:VAL120.O 73.81%
CS1:ARG646.NH2-CS1:ASP614.OD1 76.19%
BS1:VAL362.N-BS1:ASN334.O 73.17%
AS1:THR393.OG1-AS1:GLU516.OE1 73.81%
AS1:CYS336.N-AS1:VAL362.O 76.19%
AS1:CYS336.N-AS1:VAL362.O 73.17%
BS1:TYR508.N-BS1:ILE402.O 73.81%
BS1:VAL511.N-BS1:ILE434.O 76.19%
AS1:VAL551.N-AS1:THR588.O 73.17%
CS1:TYR508.N-CS1:ILE402.O 73.81%
BS1:VAL127.N-BS1:VAL120.O 76.19%
CS1:TYR423.OH-CS1:ASP398.OD2 73.17%
AS1:VAL511.N-AS1:ILE434.O 73.81%
CS2:SER1051.OG-CS2:HSE1064.ND1 73.81%
CS2:ASN928.N-CS2:ALA924.O 70.73%
AS1:PHE43.N-CS1:PHE565.O 73.81%
AS1:LEU611.N-AS1:SER596.O 73.81%
CS2:GLY885.N-CS2:GLY880.O 70.73%
CS2:VAL1068.N-CS2:THR719.O 71.43%
AS1:LEU585.N-AS1:VAL576.O 73.81%
CS2:TYR1067.N-CS2:TYR1047.O 70.73%
BS1:ILE598.N-BS1:ALA609.O 71.43%
CS1:TYR91.N-CS1:GLY268.O 73.81%
AS2:THR1066.OG1-AS2:LYS1045.O 70.73%
CS1:TYR91.N-CS1:GLY268.O 71.43%
CS1:TYR380.N-CS1:GLY431.O 73.81%
AS2:ASN777.N-AS2:GLU773.O 70.73%
CS1:ALA163.N-CS1:GLU132.O 71.43%
CS1:SER151.OG-CS1:TRP104.O 73.81%
CS1:LEU585.N-CS1:VAL576.O 70.73%
CS2:THR1066.OG1-CS2:LYS1045.O 69.05%
BS1:ILE128.N-BS1:TYR170.O 73.81%
BS1:TRP64.N-BS1:ALA27.O 70.73%
BS2:TYR695.OH-BS1:GLU661.O 69.05%
BS2:LEU1218.N-BS2:TRP1214.O 71.43%
BS1:PHE92.N-BS1:PHE192.O 70.73%
AS1:LEU611.N-AS1:SER596.O 69.05%
AS2:THR1066.N-AS2:SER721.O 71.43%
AS1:PHE194.N-AS1:VAL90.O 70.73%
BS1:TYR313.N-BS1:VAL597.O 69.05%
CS1:THR284.N-CS1:ASN280.OD1 71.43%
CS1:LEU513.N-CS1:CYS432.O 70.73%
BS1:TYR612.N-BS1:CYS649.O 69.05%
CS1:VAL551.N-CS1:THR588.O 71.43%
AS1:VAL512.N-AS1:ASP398.O 70.73%
AS1:ARG44.NH1-AS1:ASP40.OD2 69.05%
AS1:ARG34.NH2-AS1:GLU191.OE2 71.43%
CS2:PHE1089.N-CS2:PHE1121.O 70.73%
BS1:ILE587.N-BS1:ASP574.O 69.05%
AS1:TYR91.N-AS1:GLY268.O 71.43%
AS2:THR791.OG1-CS2:VAL705.O 70.73%
AS1:LEU84.N-AS1:PHE238.O 69.05%
CS1:VAL511.N-CS1:ILE434.O 71.43%
AS1:ARG685.NH2-AS2:ASP830.OD2 70.73%
AS1:LEU118.N-AS1:LYS129.O 69.05%
BS1:TYR380.N-BS1:GLY431.O 71.43%
CS1:VAL510.N-CS1:PHE400.O 70.73%
BS1:TYR266.N-BS1:ALA93.O 69.05%
AS1:PHE106.N-AS1:LEU117.O 71.43%
AS1:VAL511.N-AS1:ILE434.O 70.73%
BS1:LEU117.N-BS1:PHE106.O 69.05%
BS2:TYR1215.OH-CS2:ILE1210.O 69.05%
BS2:GLU1195.N-BS2:LYS1191.O 68.29%
BS1:CYS336.N-BS1:VAL362.O 69.05%
AS2:ASN928.N-AS2:ALA924.O 69.05%
AS2:HSD1088.N-AS2:ILE1081.O 68.29%
AS1:VAL512.N-AS1:ASP398.O 69.05%
AS2:THR1066.OG1-AS2:LYS1045.O 69.05%
AS1:TYR313.OH-AS1:GLU309.O 68.29%
BS1:TYR91.OH-BS1:GLU191.OE2 69.05%
AS2:SER1051.OG-AS2:HSE1064.ND1 69.05%
BS1:PHE43.N-AS1:PHE565.O 68.29%
BS1:ILE434.N-BS1:VAL511.O 69.05%
(continued)
384
10 Spike (S) Glycoprotein N165A and N234A Mutant
Table 10.5 (continued) Replica 4
Replica 5
Replica 6
BS2:ARG1039.NE-BS2:GLU1031.OE2 69.05%
BS1:VAL511.N-BS1:ILE434.O 68.29%
AS2:THR716.OG1-AS2:GLN1071.O 69.05%
AS2:VAL729.N-AS2:HSD1058.O 69.05%
AS1:ILE434.N-AS1:VAL511.O 68.29%
AS2:THR1231.OG1-AS2:ILE1227.O 66.67%
CS1:ARG646.NE-CS1:ASP614.OD2 69.05%
AS2:MET902.N-AS2:PHE898.O 68.29%
CS2:HSD1088.N-CS2:ILE1081.O 66.67%
BS1:LEU277.N-BS1:HSE49.O 69.05%
AS1:TYR91.N-AS1:GLY268.O 68.29%
AS2:THR1077.OG1-AS2:PHE1095.O 66.67%
CS1:ARG34.NH1-CS1:GLU191.OE1 69.05%
CS1:ASP578.N-CS1:GLU583.O 68.29%
AS2:TYR1067.N-AS2:TYR1047.O 66.67%
CS1:HSD69.N-CS1:PHE79.O 69.05%
AS1:PHE92.N-AS1:PHE192.O 68.29%
CS2:GLU1031.N-CS2:THR1027.O 66.67%
BS1:LEU84.N-BS1:PHE238.O 69.05%
AS2:SER1051.OG-AS2:HSE1064.ND1 68.29%
BS2:PHE1062.N-BS2:GLU725.O 66.67%
BS1:ILE119.N-BS1:TRP104.O 69.05%
CS1:ARG454.NE-CS1:ASP467.OD1 68.29%
BS2:ASP737.N-BS2:GLY857.O 66.67%
BS1:PHE106.N-BS1:LEU117.O 69.05%
AS2:ILE1221.N-AS2:TRP1217.O 65.85%
AS1:TYR266.N-AS1:ALA93.O 66.67%
BS1:CYS336.N-BS1:VAL362.O 69.05%
AS2:CYS1082.N-AS2:VAL1133.O 65.85%
AS1:VAL576.N-AS1:LEU585.O 66.67%
CS2:CYS1082.N-CS2:VAL1133.O 69.05%
CS2:PHE1075.N-CS2:ILE712.O 65.85%
CS1:TYR37.OH-CS1:LEU54.O 66.67%
CS2:ARG1039.NH1-AS2:SER1030.OG 69.05%
AS2:PHE1062.N-AS2:GLU725.O 65.85%
BS1:ILE326.N-BS1:ASN540.O 66.67%
AS1:TYR612.N-AS1:CYS649.O 69.05%
BS1:CYS671.N-BS2:TYR695.O 65.85%
CS1:TYR380.N-CS1:GLY431.O 66.67%
AS2:PHE1089.N-AS2:PHE1121.O 69.05%
AS2:ARG1019.NH1-AS2:ASN777.OD1 65.85%
BS1:VAL433.N-BS1:LYS378.O 66.67%
AS2:CYS1082.N-AS2:VAL1133.O 66.67%
AS1:LEU585.N-AS1:VAL576.O 65.85%
BS2:VAL1096.N-BS2:PHE1103.O 66.67%
AS2:MET902.N-AS2:PHE898.O 66.67%
AS1:TYR91.OH-AS1:GLU191.OE1 65.85%
CS1:VAL551.N-CS1:THR588.O 66.67%
BS2:THR1066.OG1-BS2:LYS1045.O 66.67%
AS1:TYR37.OH-AS1:LEU54.O 65.85%
CS1:ARG44.NH2-CS1:ASP40.OD2 66.67%
BS2:SER1037.OG-BS2:GLU1031.OE2 66.67%
AS1:LEU229.N-AS1:PHE201.O 65.85%
BS1:TYR91.N-BS1:GLY268.O 66.67%
BS2:TYR695.N-BS1:CYS671.O 66.67%
BS1:TYR380.N-BS1:GLY431.O 65.85%
AS2:THR883.OG1-AS2:ALA879.O 66.67%
AS1:TYR313.OH-AS1:GLU309.O 66.67%
BS1:CYS336.N-BS1:VAL362.O 65.85%
AS2:ASN777.N-AS2:GLU773.O 66.67%
CS1:LEU277.N-CS1:HSE49.O 66.67%
BS1:LEU118.N-BS1:LYS129.O 65.85%
BS2:ILE742.N-BS2:CYS738.O 66.67%
AS1:GLN271.N-AS1:PHE55.O 66.67%
AS1:LEU118.N-AS1:LYS129.O 65.85%
BS2:THR1077.OG1-BS2:PHE1095.O 64.29%
CS1:TYR269.OH-CS1:PRO85.O 66.67%
CS2:PHE1052.N-CS2:LEU1063.O 65.85%
CS2:ASN777.N-CS2:GLU773.O 64.29%
AS1:LEU241.N-AS1:GLY103.O 66.67%
AS1:ARG319.NH1-AS1:CYS590.O 65.85%
AS1:TYR313.N-AS1:VAL597.O 64.29%
CS1:VAL433.N-CS1:LYS378.O 66.67%
BS1:LYS202.N-BS1:LYS195.O 65.85%
AS1:PHE275.N-AS1:THR51.O 64.29%
CS1:VAL130.N-CS1:GLU169.OE2 66.67%
CS1:VAL362.N-CS1:ASN334.O 65.85%
CS1:ASN536.N-CS1:LEU552.O 64.29%
AS1:VAL551.N-AS1:THR588.O 66.67%
CS1:CYS671.N-CS2:TYR695.O 65.85%
AS1:PHE192.N-AS1:PHE92.O 64.29%
CS1:LEU585.N-CS1:VAL576.O 66.67%
AS1:PHE392.N-AS1:VAL524.O 65.85%
BS1:ARG44.NH2-BS1:ASP40.OD2 64.29%
BS1:VAL433.N-BS1:LYS378.O 66.67%
BS2:THR1238.OG1-BS2:LEU1234.O 63.41%
BS1:LEU585.N-BS1:VAL576.O 64.29%
BS1:LEU560.N-BS1:GLN563.OE1 66.67%
CS2:CYS1082.N-CS2:VAL1133.O 63.41%
AS1:LEU241.N-AS1:GLY103.O 64.29%
AS2:TYR1067.N-AS2:TYR1047.O 64.29%
BS2:VAL1096.N-BS2:PHE1103.O 63.41%
BS1:LEU223.N-BS1:VAL36.O 64.29%
AS2:ALA879.N-AS2:SER875.O 64.29%
AS2:PHE1075.N-AS2:ILE712.O 63.41%
CS1:VAL362.N-CS1:ASN334.O 64.29%
CS2:ARG1039.NE-CS2:GLU1031.OE2 64.29%
CS2:SER884.OG-CS2:LEU894.O 63.41%
AS1:PHE392.N-AS1:VAL524.O 64.29%
CS2:ILE788.N-BS2:ALA701.O 64.29%
CS2:THR883.OG1-CS2:ALA879.O 63.41%
BS1:VAL511.N-BS1:ILE434.O 64.29%
CS2:GLU1031.N-CS2:THR1027.O 64.29%
BS2:THR1066.N-BS2:SER721.O 63.41%
BS2:SER1051.OG-BS2:HSE1064.ND1 64.29%
CS2:TYR695.OH-CS1:GLU661.O 64.29%
AS2:PHE1052.N-AS2:LEU1063.O 63.41%
BS2:ALA879.N-BS2:SER875.O 64.29%
BS2:VAL729.N-BS2:HSD1058.O 64.29%
BS1:TYR612.N-BS1:CYS649.O 63.41%
BS1:LEU277.N-BS1:HSE49.O 64.29%
AS2:ASN777.N-AS2:GLU773.O 64.29%
CS1:GLN271.N-CS1:PHE55.O 63.41%
AS1:PHE92.N-AS1:PHE192.O 64.29%
BS1:PHE92.N-BS1:PHE192.O 64.29%
AS1:GLN271.N-AS1:PHE55.O 63.41%
CS1:LYS202.N-CS1:LYS195.O 64.29%
BS1:LEU118.N-BS1:LYS129.O 64.29%
CS1:PHE65.N-CS1:TYR265.O 63.41%
AS1:ILE128.N-AS1:TYR170.O 64.29%
AS1:LEU118.N-AS1:LYS129.O 64.29%
CS1:LYS202.N-CS1:LYS195.O 63.41%
AS1:TYR396.N-AS1:SER514.O 64.29%
BS2:CYP1241.N-BS2:CYS1236.O 64.29%
BS1:ILE358.N-BS1:VAL395.O 63.41%
AS2:MET1229.N-AS2:ILE1225.O 61.9%
CS1:ILE587.N-CS1:ASP574.O 64.29%
BS2:PHE802.N-BS2:LYS795.O 63.41%
AS2:PHE1089.N-AS2:PHE1121.O 61.9%
CS1:SER555.OG-CS1:ASP586.OD2 64.29%
CS1:TYR37.OH-CS1:LEU54.O 63.41%
AS2:LEU1034.N-AS2:MET1029.O 61.9%
BS1:ILE434.N-BS1:VAL511.O 64.29%
BS2:TYR695.OH-BS1:SER673.O 63.41%
BS2:ASN928.N-BS2:ALA924.O 61.9%
BS1:VAL512.N-BS1:ASP398.O 64.29%
CS2:ASP737.N-CS2:GLY857.O 63.41%
BS2:LEU1034.N-BS2:MET1029.O 61.9%
AS1:TYR451.OH-AS1:ASP442.OD1 64.29%
BS1:TYR91.N-BS1:GLY268.O 63.41%
CS2:LEU1063.N-CS2:PHE1052.O 61.9%
AS1:SER438.OG-AS1:ASP442.OD2 64.29%
CS1:LEU611.N-CS1:SER596.O 63.41%
BS2:GLN1054.N-BS2:VAL1061.O 61.9%
BS2:GLU1195.N-BS2:LYS1191.O 61.9%
BS1:CYS617.N-BS1:GLN644.OE1 63.41%
CS1:ALA668.N-AS2:PRO863.O 61.9%
AS2:VAL1096.N-AS2:PHE1103.O 61.9%
AS2:ASN928.N-AS2:ALA924.O 60.98%
AS1:CYS671.N-AS2:TYR695.O 61.9%
CS2:ALA879.N-CS2:SER875.O 61.9%
BS2:TYR1067.N-BS2:TYR1047.O 60.98%
CS1:ARG646.NH2-CS1:ASP614.OD2 61.9%
AS2:GLU1031.N-AS2:THR1027.O 61.9%
CS2:THR1066.N-CS2:SER721.O 60.98%
AS1:LEU277.N-AS1:HSE49.O 61.9%
AS2:ARG1019.NH1-AS2:ASN777.OD1 61.9%
AS2:THR883.OG1-AS2:ALA879.O 60.98%
CS2:ILE997.N-CS2:ILE993.O 61.9%
BS1:TYR313.N-BS1:VAL597.O 61.9%
AS2:ALA879.N-AS2:SER875.O 60.98%
AS1:PHE543.N-AS1:LEU546.O 61.9%
CS1:TYR313.N-CS1:VAL597.O 61.9%
CS2:LEU938.N-CS2:ILE934.O 60.98%
BS1:PHE92.N-BS1:PHE192.O 61.9%
AS2:SER1003.OG-AS2:GLY999.O 61.9%
CS1:TYR313.OH-CS1:GLU309.O 60.98%
BS1:LYS202.N-BS1:LYS195.O 61.9%
AS1:ARG567.NE-AS1:ASP571.OD2 61.9%
BS1:ILE598.N-BS1:ALA609.O 60.98%
BS1:TRP64.N-BS1:ALA27.O 61.9%
AS1:TYR266.N-AS1:ALA93.O 61.9%
AS1:ILE598.N-AS1:ALA609.O 60.98%
BS1:LEU84.N-BS1:PHE238.O 61.9%
BS1:ILE358.N-BS1:VAL395.O 61.9%
BS2:VAL1008.N-BS2:LEU1004.O 60.98%
CS2:THR1077.OG1-CS2:PHE1095.O 61.9%
AS1:ILE128.N-AS1:TYR170.O 61.9%
CS1:LEU277.N-CS1:HSE49.O 60.98%
BS2:VAL1061.N-BS2:GLN1054.O 61.9%
BS1:LEU117.N-BS1:PHE106.O 61.9%
CS1:ARG273.N-CS1:ASP53.O 60.98%
AS2:ALA1022.N-AS2:ILE1018.O 61.9%
CS1:ASP398.N-CS1:VAL512.O 61.9%
AS1:ARG34.NH2-AS1:GLU191.OE2 60.98%
AS1:PHE318.N-AS1:GLY593.O 61.9%
CS1:ARG355.NE-CS1:ASP398.OD1 61.9%
AS1:ARG44.NH2-AS1:ASP40.OD2 60.98%
BS1:TYR37.OH-BS1:LEU54.O 61.9%
CS1:VAL362.N-CS1:ASN334.O 61.9%
AS1:THR323.N-AS1:CYS538.O 60.98%
CS2:SER875.OG-CS2:ALA871.O 61.9%
CS1:CYS336.N-CS1:VAL362.O 61.9%
CS1:TYR269.OH-CS1:PRO85.O 60.98%
CS2:VAL729.N-CS2:HSD1058.O 61.9%
(continued)
Supplementary Information
385
Table 10.5 (continued) Replica 4
Replica 5
Replica 6
AS1:ILE434.N-AS1:VAL511.O 61.9%
BS1:ILE119.N-BS1:TRP104.O 60.98%
CS1:VAL597.N-CS1:TYR313.O 61.9%
BS2:VAL1104.N-BS2:GLN1113.O 61.9%
CS1:GLN493.N-CS1:TYR453.O 60.98%
CS1:PHE92.N-CS1:PHE192.O 61.9%
CS2:ASN928.N-CS2:ALA924.O 61.9%
AS2:VAL1096.N-AS2:PHE1103.O 60.98%
AS1:GLN493.N-AS1:TYR453.O 61.9%
BS1:ILE598.N-BS1:ALA609.O 61.9%
CS2:HSE1064.N-CS2:THR723.O 60.98%
CS1:LEU513.N-CS1:CYS432.O 61.9%
AS1:LEU189.N-AS1:THR208.O 61.9%
CS1:VAL511.N-CS1:ILE434.O 60.98%
BS2:ASN928.N-BS2:ALA924.O 61.9%
BS2:THR883.OG1-BS2:ALA879.O 60.98%
BS1:THR299.OG1-BS1:PRO295.O 61.9%
BS1:LEU611.N-BS1:SER596.O 60.98%
CS1:THR523.OG1-CS1:THR393.O 61.9%
AS1:ASP578.N-AS1:GLU583.O 60.98% BS1:PHE194.N-BS1:VAL90.O 60.98%
Table 10.6 The HBs with more than 60% occupancy rates of the wild-type from the analyses of the 1 μs’ (replicas 1–3) MD trajectories of [55] Replica 1
Replica 2
Replica 3
CS2:TYR695.OH-CS1:GLU661.O 77.23%
CS1:ARG355.NE-CS1:ASP398.OD1 86.14%
BS2:TYR695.OH-BS1:GLU661.O 78.22%
CS1:ASP420.N-CS1:GLY416.O 73.27%
AS1:ILE598.N-AS1:ALA609.O 80.2%
BS1:PHE43.N-AS1:PHE565.O 77.23%
BS1:ARG44.NH2-BS1:ASP40.OD2 73.27%
CS1:TYR351.OH-CS1:ASP467.OD2 78.22%
BS1:LEU118.N-BS1:LYS129.O 77.23%
BS2:SER1051.OG-BS2:HSE1064.ND1 72.28%
AS1:TYR37.OH-AS1:LEU54.O 76.24%
AS1:LEU277.N-AS1:HSE49.O 74.26%
CS2:SER1051.OG-CS2:HSE1064.ND1 72.28%
BS1:ARG567.NH2-CS2:ASP979.OD1 76.24%
BS1:TYR91.OH-BS1:GLU191.OE1 74.26%
AS1:LEU611.N-AS1:SER596.O 72.28%
BS2:TYR695.OH-BS1:GLU661.O 74.26%
CS1:TYR91.N-CS1:GLY268.O 74.26%
BS1:LYS202.N-BS1:LYS195.O 72.28%
BS2:SER1051.OG-BS2:HSE1064.ND1 73.27%
AS1:LEU118.N-AS1:LYS129.O 74.26%
BS1:ILE598.N-BS1:ALA609.O 71.29%
CS1:VAL511.N-CS1:ILE434.O 73.27%
BS1:VAL511.N-BS1:ILE434.O 74.26%
BS1:TYR91.N-BS1:GLY268.O 71.29%
BS1:ILE598.N-BS1:ALA609.O 72.28%
AS1:VAL511.N-AS1:ILE434.O 73.27%
AS1:PHE543.N-AS1:LEU546.O 71.29%
AS1:VAL127.N-AS1:VAL120.O 72.28%
BS2:SER1051.OG-BS2:HSE1064.ND1 73.27%
CS1:SER151.OG-CS1:TRP104.O 71.29%
BS1:LEU118.N-BS1:LYS129.O 72.28%
BS1:ILE598.N-BS1:ALA609.O 71.29%
CS1:ARG454.N-CS1:ASN422.OD1 71.29%
AS1:LEU513.N-AS1:CYS432.O 72.28%
BS1:LEU277.N-BS1:HSE49.O 70.3%
BS1:LEU611.N-BS1:SER596.O 71.29%
AS1:PHE43.N-CS1:PHE565.O 71.29%
BS1:LEU611.N-BS1:SER596.O 70.3%
AS1:SER438.OG-AS1:ASP442.OD2 71.29%
CS1:LEU585.N-CS1:VAL576.O 71.29%
CS1:VAL511.N-CS1:ILE434.O 70.3%
AS1:TYR37.OH-AS1:LEU54.O 70.3%
BS1:LEU611.N-BS1:SER596.O 71.29%
CS1:ILE598.N-CS1:ALA609.O 69.31%
CS1:VAL511.N-CS1:ILE434.O 70.3%
CS1:TYR37.OH-CS1:LEU54.O 71.29%
BS1:TYR508.N-BS1:ILE402.O 69.31%
BS2:TYR695.OH-BS1:GLU661.O 69.31%
CS1:PHE275.N-CS1:THR51.O 70.3%
AS1:TYR91.N-AS1:GLY268.O 67.33%
CS1:LEU277.N-CS1:HSE49.O 69.31%
BS1:ARG403.NH2-BS1:ASP405.OD2 70.3%
BS2:THR1066.OG1-BS2:LYS1045.O 67.33%
BS1:PHE43.N-AS1:PHE565.O 69.31%
BS2:THR1066.OG1-BS2:LYS1045.O 70.3%
CS1:TYR313.OH-CS1:GLU309.O 67.33%
CS2:THR883.OG1-CS2:ALA879.O 69.31%
CS2:SER1051.OG-CS2:HSE1064.ND1 70.3%
CS1:LEU585.N-CS1:VAL576.O 67.33%
AS1:VAL551.N-AS1:THR588.O 68.32%
AS1:ARG158.NE-AS1:GLU156.OE1 70.3%
AS1:PHE106.N-AS1:LEU117.O 66.34%
AS1:PHE43.N-CS1:PHE565.O 68.32%
BS2:VAL1008.N-BS2:LEU1004.O 69.31%
AS2:SER1051.OG-AS2:HSE1064.ND1 66.34%
BS1:TYR37.OH-BS1:LEU54.O 68.32%
BS1:ARG457.N-BS1:ASP420.OD1 69.31%
AS1:ILE598.N-AS1:ALA609.O 66.34%
BS1:TYR380.N-BS1:GLY431.O 68.32%
CS1:ARG408.NH1-BS1:ASP405.OD1 69.31%
BS2:ILE742.N-BS2:CYS738.O 66.34%
AS1:LEU118.N-AS1:LYS129.O 68.32%
CS2:THR1066.N-CS2:SER721.O 68.32%
CS2:CYS1082.N-CS2:VAL1133.O 66.34%
BS1:SER673.OG-BS1:ASP663.OD1 68.32%
BS1:TRP64.N-BS1:ALA27.O 68.32%
BS2:THR1066.N-BS2:SER721.O 65.35%
BS1:VAL511.N-BS1:ILE434.O 68.32%
AS1:TYR91.N-AS1:GLY268.O 68.32%
AS1:ILE651.N-AS1:VAL610.O 65.35%
AS2:ASN928.N-AS2:ALA924.O 67.33%
AS2:ASN777.N-AS2:GLU773.O 68.32%
BS1:PHE106.N-BS1:LEU117.O 65.35%
AS1:ILE598.N-AS1:ALA609.O 67.33%
AS1:LEU277.N-AS1:HSE49.O 68.32%
AS2:THR1066.OG1-AS2:LYS1045.O 65.35%
AS1:ILE651.N-AS1:VAL610.O 67.33%
AS1:ARG509.NH2-AS1:ASP442.OD2 68.32%
CS2:SER1051.OG-CS2:HSE1064.ND1 65.35%
CS2:TYR1067.N-CS2:TYR1047.O 67.33%
AS1:VAL511.N-AS1:ILE434.O 67.33%
AS1:LEU611.N-AS1:SER596.O 65.35%
AS2:ASN777.N-AS2:GLU773.O 67.33%
BS1:ILE128.N-BS1:TYR170.O 67.33%
CS1:VAL551.N-CS1:THR588.O 65.35%
AS1:VAL511.N-AS1:ILE434.O 67.33%
CS1:ARG355.NH2-CS1:ASP398.OD2 67.33%
BS1:ARG34.NH2-BS1:GLU191.OE2 65.35%
AS1:TYR451.OH-AS1:ASP442.OD1 66.34%
CS1:SER366.OG-CS1:ASP364.OD2 67.33%
AS2:THR1066.N-AS2:SER721.O 64.36%
AS2:SER1051.OG-AS2:HSE1064.ND1 66.34%
AS1:LEU611.N-AS1:SER596.O 67.33%
AS2:GLU1031.N-AS2:THR1027.O 64.36%
AS1:LEU277.N-AS1:HSE49.O 66.34%
CS1:ARG34.NH2-CS1:GLU191.OE1 67.33%
AS1:TYR380.N-AS1:GLY431.O 64.36%
CS1:LEU585.N-CS1:VAL576.O 66.34%
CS2:ALA879.N-CS2:SER875.O 66.34%
AS1:LEU585.N-AS1:VAL576.O 64.36%
AS1:PHE65.N-AS1:TYR265.O 66.34%
CS2:THR1066.OG1-CS2:LYS1045.O 66.34%
BS1:LEU585.N-BS1:VAL576.O 64.36%
BS1:VAL512.N-BS1:ASP398.O 66.34%
CS2:ASN777.N-CS2:GLU773.O 66.34%
BS1:ARG34.NE-BS1:GLU191.OE1 64.36%
AS2:ALA879.N-AS2:SER875.O 66.34%
AS1:LEU585.N-AS1:VAL576.O 66.34%
CS2:THR1066.OG1-CS2:LYS1045.O 63.37%
BS2:THR883.OG1-BS2:ALA879.O 65.35%
AS1:LEU118.N-AS1:LYS129.O 66.34%
BS2:ILE997.N-BS2:ILE993.O 63.37%
CS2:ILE923.N-CS2:ASN919.O 64.36%
AS1:TYR313.N-AS1:VAL597.O 65.35%
CS1:TRP64.N-CS1:ALA27.O 63.37%
BS1:LEU118.N-BS1:LYS129.O 64.36%
CS1:TYR91.OH-CS1:GLU191.OE2 65.35%
AS1:ASP578.N-AS1:GLU583.O 63.37%
BS2:CYS1082.N-BS2:VAL1133.O 64.36%
AS1:ILE128.N-AS1:TYR170.O 65.35%
CS1:VAL510.N-CS1:PHE400.O 63.37%
BS1:TYR612.N-BS1:CYS649.O 64.36%
BS1:CYS336.N-BS1:VAL362.O 65.35%
CS1:LEU277.N-CS1:HSE49.O 63.37%
(continued)
386
10 Spike (S) Glycoprotein N165A and N234A Mutant
Table 10.6 (continued) Replica 1
Replica 2
Replica 3
CS2:THR1077.OG1-CS2:PHE1095.O 64.36%
AS1:ARG328.NE-AS1:ASP578.OD2 65.35%
AS1:PHE65.N-AS1:TYR265.O 63.37%
AS1:ARG44.NH2-AS1:ASP40.OD2 63.37%
CS1:ARG34.NE-CS1:GLU191.OE2 65.35%
AS2:THR1077.OG1-AS2:PHE1095.O 63.37%
AS1:TYR91.N-AS1:GLY268.O 63.37%
CS2:GLU1031.N-CS2:THR1027.O 64.36%
BS2:LYS733.NZ-BS2:ASP775.OD2 62.38%
AS1:ILE434.N-AS1:VAL511.O 63.37%
AS2:VAL1008.N-AS2:LEU1004.O 64.36%
CS1:SER596.N-CS1:LEU611.O 62.38%
AS1:TYR508.N-AS1:ILE402.O 63.37%
AS1:PHE275.N-AS1:THR51.O 64.36%
AS1:TYR37.OH-AS1:LEU54.O 62.38%
CS1:TYR313.OH-CS1:GLU309.O 63.37%
CS1:PHE543.N-CS1:LEU546.O 64.36%
BS1:PHE543.N-BS1:LEU546.O 62.38%
AS1:ASP578.N-AS1:GLU583.O 63.37%
BS1:VAL362.N-BS1:ASN334.O 64.36%
CS1:LYS202.N-CS1:LYS195.O 62.38%
BS2:ALA1022.N-BS2:ILE1018.O 63.37%
AS2:THR1066.OG1-AS2:LYS1045.O 64.36%
CS1:VAL433.N-CS1:LYS378.O 62.38%
AS1:ARG509.NE-AS1:ASP442.OD2 63.37%
AS1:PHE106.N-AS1:LEU117.O 64.36%
BS2:THR1077.OG1-BS2:PHE1095.O 62.38%
AS1:LYS202.N-AS1:LYS195.O 62.38%
CS1:TYR313.N-CS1:VAL597.O 63.37%
AS2:ALA879.N-AS2:SER875.O 62.38%
BS1:VAL127.N-BS1:VAL120.O 62.38%
BS1:ILE358.N-BS1:VAL395.O 63.37%
AS2:PHE1052.N-AS2:LEU1063.O 62.38%
BS1:CYS336.N-BS1:VAL362.O 62.38%
BS1:VAL512.N-BS1:ASP398.O 63.37%
BS1:TYR380.N-BS1:GLY431.O 62.38%
AS1:PHE106.N-AS1:LEU117.O 62.38%
AS1:ILE434.N-AS1:VAL511.O 63.37%
CS1:ILE434.N-CS1:VAL511.O 62.38%
BS2:ALA879.N-BS2:SER875.O 62.38%
BS1:TYR91.N-BS1:GLY268.O 63.37%
AS2:TYR1067.N-AS2:TYR1047.O 61.39%
BS1:LEU277.N-BS1:HSE49.O 62.38%
BS2:ILE693.N-BS1:SER673.O 63.37%
BS1:TYR612.N-BS1:CYS649.O 61.39%
CS2:GLU1031.N-CS2:THR1027.O 61.39%
BS1:ARG567.NH1-CS2:ASP979.OD2 63.37%
BS1:TYR37.OH-BS1:LEU54.O 61.39%
CS2:ASN777.N-CS2:GLU773.O 61.39%
BS2:THR1077.OG1-BS2:PHE1095.O 62.38%
BS1:PHE275.N-BS1:THR51.O 61.39%
BS1:ILE651.N-BS1:VAL610.O 61.39%
BS2:TYR1067.N-BS2:TYR1047.O 62.38%
CS1:ARG102.N-CS1:LEU241.O 61.39%
CS1:ILE587.N-CS1:ASP574.O 61.39%
BS2:THR883.OG1-BS2:ALA879.O 62.38%
AS1:GLY381.N-CS1:PHE490.O 61.39%
CS1:ASP578.N-CS1:GLU583.O 61.39%
BS2:GLU1031.N-BS2:THR1027.O 62.38%
BS2:THR1231.OG1-BS2:ILE1227.O 60.4%
CS2:LEU1063.N-CS2:PHE1052.O 61.39%
BS1:VAL267.N-BS1:THR63.O 62.38%
CS2:HSD1088.N-CS2:ILE1081.O 60.4%
AS1:LEU585.N-AS1:VAL576.O 61.39%
BS1:TYR313.OH-BS1:GLU309.O 62.38%
CS2:ASN928.N-CS2:ALA924.O 60.4%
BS1:PHE106.N-BS1:LEU117.O 61.39%
BS1:VAL551.N-BS1:THR588.O 62.38%
AS1:TYR313.N-AS1:VAL597.O 60.4%
BS2:VAL1096.N-BS2:PHE1103.O 61.39%
BS1:VAL433.N-BS1:LYS378.O 62.38%
AS1:VAL551.N-AS1:THR588.O 60.4%
BS2:ASN928.N-BS2:ALA924.O 61.39%
BS1:ARG102.N-BS1:LEU241.O 62.38%
BS1:VAL62.N-BS1:THR29.O 60.4%
AS1:PHE92.N-AS1:PHE192.O 61.39%
AS1:ARG509.NE-AS1:ASP442.OD1 62.38%
AS1:GLN493.N-AS1:TYR453.O 60.4%
BS2:THR1066.N-BS2:SER721.O 60.4%
AS2:VAL1096.N-AS2:PHE1103.O 61.39%
BS2:LEU1063.N-BS2:PHE1052.O 60.4%
CS1:TYR269.OH-CS1:PRO85.O 60.4%
AS2:GLU1031.N-AS2:THR1027.O 61.39%
AS2:LEU1063.N-AS2:PHE1052.O 60.4%
AS2:VAL1096.N-AS2:PHE1103.O 60.4%
AS1:VAL512.N-AS1:ASP398.O 61.39%
CS1:TYR313.N-CS1:VAL597.O 60.4%
BS1:ASP578.N-BS1:GLU583.O 60.4%
CS2:VAL1096.N-CS2:PHE1103.O 61.39%
CS1:ILE128.N-CS1:TYR170.O 60.4%
CS1:PHE92.N-CS1:PHE192.O 60.4%
BS1:LEU277.N-BS1:HSE49.O 61.39%
BS1:LYS202.N-BS1:LYS195.O 60.4%
CS1:ASP398.N-CS1:VAL512.O 60.4%
CS2:SER974.OG-CS2:ASP979.OD2 61.39%
CS2:LEU1063.N-CS2:PHE1052.O 60.4%
BS1:GLN271.N-BS1:PHE55.O 60.4%
BS1:ARG454.N-BS1:ASN422.OD1 61.39%
CS1:TYR91.OH-CS1:GLU191.OE1 60.4%
BS1:TYR380.N-BS1:GLY431.O 61.39%
BS1:ARG44.NH2-BS1:ASP40.OD2 60.4%
CS1:LEU513.N-CS1:CYS432.O 61.39% BS2:ILE997.N-BS2:ILE993.O 61.39% AS1:ILE587.N-AS1:ASP574.O 60.4% AS1:THR323.N-AS1:CYS538.O 60.4% BS2:THR1238.OG1-BS2:LEU1234.O 60.4% AS2:TYR1067.N-AS2:TYR1047.O 60.4% CS1:TYR313.OH-CS1:GLU309.O 60.4% CS1:LEU277.N-CS1:HSE49.O 60.4% BS2:ILE1232.N-BS2:VAL1228.O 60.4% AS2:CYS1082.N-AS2:VAL1133.O 60.4% BS2:PHE1062.N-BS2:GLU725.O 60.4% BS1:TYR269.OH-BS1:PRO85.O 60.4%
Supplementary Information
387
Table 10.7 The HBs with more than 60% occupancy rates of the wild-type from the analyses of the 400 ns’ (replicas 4–6) MD trajectories of [55] Replica 4
Replica 5
Replica 6
CS1:THR581.OG1-CS1:ASP578.OD1 85.37%
BS2:TYR695.OH-BS1:GLU661.O 82.93%
CS1:ARG355.NE-CS1:ASP398.OD1 85.37%
CS1:SER316.OG-AS2:ASP737.OD2 82.93%
BS1:PHE43.N-AS1:PHE565.O 82.93%
AS1:VAL127.N-AS1:VAL120.O 80.49%
AS1:VAL511.N-AS1:ILE434.O 82.93%
BS2:SER1051.OG-BS2:HSE1064.ND1 78.05%
CS2:SER1051.OG-CS2:HSE1064.ND1 78.05%
BS2:TYR695.OH-BS1:GLU661.O 80.49%
BS1:LEU118.N-BS1:LYS129.O 78.05%
CS1:TYR351.OH-CS1:ASP467.OD2 78.05%
CS2:SER974.OG-CS2:ASP979.OD1 78.05%
CS1:TYR91.OH-CS1:GLU191.OE2 75.61%
AS1:THR323.N-AS1:CYS538.O 75.61%
BS1:ARG509.NH1-BS1:ASP442.OD1 78.05%
AS1:PHE106.N-AS1:LEU117.O 75.61%
BS1:PHE43.N-AS1:PHE565.O 75.61%
AS1:ILE598.N-AS1:ALA609.O 75.61%
BS1:GLN493.N-BS1:TYR453.O 75.61%
CS1:TYR37.OH-CS1:LEU54.O 75.61%
BS1:ILE598.N-BS1:ALA609.O 75.61%
BS2:ASN928.N-BS2:ALA924.O 73.17%
AS1:VAL510.N-AS1:PHE400.O 75.61%
AS1:LEU277.N-AS1:HSE49.O 75.61%
AS2:THR1066.OG1-AS2:LYS1045.O 73.17%
AS1:ARG509.NE-AS1:ASP442.OD1 75.61%
CS1:ARG328.NH2-CS1:ASP578.OD1 75.61%
AS1:TYR313.OH-AS1:GLU309.O 73.17%
CS1:ILE128.N-CS1:TYR170.O 75.61%
AS2:THR1077.OG1-AS2:PHE1095.O 75.61%
BS1:TYR37.OH-BS1:LEU54.O 73.17%
AS2:VAL1096.N-AS2:PHE1103.O 73.17%
BS1:ARG44.NH2-BS1:ASP40.OD2 75.61%
AS1:TYR396.N-AS1:SER514.O 73.17%
CS2:THR1066.OG1-CS2:LYS1045.O 73.17%
AS1:ARG509.NE-AS1:ASP442.OD1 75.61%
AS1:VAL511.N-AS1:ILE434.O 73.17%
CS2:GLU1031.N-CS2:THR1027.O 73.17%
BS2:HSD1088.N-BS2:ILE1081.O 73.17%
CS2:PHE1089.N-CS2:PHE1121.O 73.17%
AS1:ILE651.N-AS1:VAL610.O 73.17%
BS2:TYR1067.N-BS2:TYR1047.O 73.17%
CS1:LEU585.N-CS1:VAL576.O 73.17%
AS1:LEU585.N-AS1:VAL576.O 73.17%
BS2:PHE1062.N-BS2:GLU725.O 73.17%
BS2:THR1077.OG1-BS2:PHE1095.O 70.73%
CS1:LEU585.N-CS1:VAL576.O 73.17%
BS2:ILE693.N-BS1:SER673.O 73.17%
AS1:PHE92.N-AS1:PHE192.O 70.73%
BS2:PHE1062.N-BS2:GLU725.O 70.73%
CS1:LEU585.N-CS1:VAL576.O 73.17%
CS1:TYR91.N-CS1:GLY268.O 70.73%
AS1:PHE275.N-AS1:THR51.O 70.73%
BS1:ARG567.NH2-CS2:ASP979.OD2 73.17%
AS1:CYS336.N-AS1:VAL362.O 70.73%
BS1:VAL62.N-BS1:THR29.O 70.73%
AS1:TYR508.N-AS1:ILE402.O 73.17%
BS1:CYS336.N-BS1:VAL362.O 70.73%
AS1:TYR91.N-AS1:GLY268.O 70.73%
BS2:CYS1082.N-BS2:VAL1133.O 70.73%
BS2:THR1066.OG1-BS2:LYS1045.O 68.29%
BS1:ARG567.NH2-CS2:ASP979.OD1 70.73%
CS2:PHE1089.N-CS2:PHE1121.O 70.73%
CS2:THR1066.OG1-CS2:LYS1045.O 68.29%
BS1:TYR269.OH-BS1:PRO85.O 70.73%
AS2:GLU918.N-AS2:ASN914.O 70.73%
AS1:ARG44.NH2-AS1:ASP40.OD2 68.29%
CS1:VAL511.N-CS1:ILE434.O 70.73%
BS2:GLU1031.N-BS2:THR1027.O 70.73%
AS1:TYR37.OH-AS1:LEU54.O 68.29%
AS1:VAL511.N-AS1:ILE434.O 70.73%
AS2:VAL729.N-AS2:HSD1058.O 70.73%
AS1:PHE65.N-AS1:TYR265.O 68.29%
AS1:TYR91.OH-AS1:GLU191.OE1 70.73%
CS1:GLN613.N-CS1:GLY594.O 70.73%
AS1:LYS77.NZ-AS1:ASP138.OD1 68.29%
BS1:ARG567.NH1-CS2:ASP979.OD2 70.73%
BS1:PHE43.N-AS1:PHE565.O 70.73%
CS1:TYR396.N-CS1:SER514.O 68.29%
BS2:ALA1022.N-BS2:ILE1018.O 70.73%
AS1:THR323.N-AS1:CYS538.O 70.73%
CS1:ILE434.N-CS1:VAL511.O 68.29%
AS2:GLU918.N-AS2:ASN914.O 68.29%
BS1:GLN271.N-BS1:PHE55.O 70.73%
AS1:TYR508.N-AS1:ILE402.O 68.29%
BS2:GLU1031.N-BS2:THR1027.O 68.29%
BS1:TYR266.N-BS1:ALA93.O 70.73%
AS1:LEU650.N-AS1:PHE643.O 68.29%
AS2:ALA879.N-AS2:SER875.O 68.29%
BS1:VAL511.N-BS1:ILE434.O 70.73%
CS1:VAL511.N-CS1:ILE434.O 68.29%
BS2:TYR695.OH-BS1:GLU661.O 68.29%
BS2:GLN1036.NE2-BS2:HSE1048.O 70.73%
BS1:LEU611.N-BS1:SER596.O 68.29%
CS2:ASN777.N-CS2:GLU773.O 68.29%
BS1:VAL551.N-BS1:THR588.O 70.73%
CS1:TRP64.N-CS1:ALA27.O 68.29%
AS1:LEU650.N-AS1:PHE643.O 68.29%
AS1:TYR91.N-AS1:GLY268.O 70.73%
CS2:ASN928.N-CS2:ALA924.O 65.85%
BS1:LEU650.N-BS1:PHE643.O 68.29%
BS1:LEU585.N-BS1:VAL576.O 70.73%
AS2:ALA879.N-AS2:SER875.O 65.85%
BS1:ILE598.N-BS1:ALA609.O 68.29%
CS1:ARG328.NH1-CS1:ASP578.OD2 70.73%
BS2:ARG1019.NH1-BS2:ASN777.OD1 65.85%
AS1:LEU277.N-AS1:HSE49.O 68.29%
CS1:ARG457.NH2-CS1:GLU465.OE1 70.73%
AS1:LEU611.N-AS1:SER596.O 65.85%
AS1:PHE43.N-CS1:PHE565.O 68.29%
AS1:PHE592.N-AS1:PHE318.O 70.73%
BS1:TYR612.N-BS1:CYS649.O 65.85%
AS1:PHE192.N-AS1:PHE92.O 68.29%
CS2:PHE1062.N-CS2:GLU725.O 68.29%
AS1:ILE587.N-AS1:ASP574.O 65.85%
BS1:TYR266.N-BS1:ALA93.O 68.29%
AS2:ARG1019.NH1-AS2:ASN777.OD1 68.29%
AS2:ILE997.N-AS2:ILE993.O 65.85%
BS1:VAL267.N-BS1:THR63.O 68.29%
BS1:LEU277.N-BS1:HSE49.O 68.29%
AS1:ARG44.NH1-AS1:ASP40.OD1 65.85%
AS1:LEU118.N-AS1:LYS129.O 68.29%
AS1:VAL267.N-AS1:THR63.O 68.29%
CS1:LEU223.N-CS1:VAL36.O 65.85%
AS1:ILE358.N-AS1:VAL395.O 68.29%
AS1:PHE43.N-CS1:PHE565.O 68.29%
BS1:TRP64.N-BS1:ALA27.O 65.85%
AS1:ALA397.N-AS1:LYS356.O 68.29%
AS1:PHE65.N-AS1:TYR265.O 68.29%
BS1:PHE106.N-BS1:LEU117.O 65.85%
BS1:LEU611.N-BS1:SER596.O 68.29%
CS1:VAL62.N-CS1:THR29.O 68.29%
CS1:TYR380.N-CS1:GLY431.O 65.85%
CS1:TYR423.OH-CS1:ASP398.OD2 68.29%
CS1:TYR91.OH-CS1:GLU191.OE1 68.29%
AS1:VAL120.N-AS1:VAL127.O 65.85%
BS1:ASN354.N-BS1:ASP398.OD2 68.29%
AS1:LYS202.N-AS1:LYS195.O 68.29%
BS1:VAL362.N-BS1:ASN334.O 65.85%
AS2:ASN960.N-AS2:ALA956.O 68.29%
CS1:ASP420.N-CS1:GLY416.O 68.29%
CS1:TYR489.OH-AS1:GLY381.O 65.85%
CS1:TYR91.N-CS1:GLY268.O 68.29%
BS1:ILE434.N-BS1:VAL511.O 68.29%
AS1:VAL512.N-AS1:ASP398.O 65.85%
CS2:ILE923.N-CS2:ASN919.O 65.85%
CS1:ARG454.N-CS1:ASN422.OD1 68.29%
BS1:TYR508.N-BS1:ILE402.O 65.85%
BS2:MET902.N-BS2:PHE898.O 65.85%
AS1:TYR313.N-AS1:VAL597.O 68.29%
BS2:THR1066.N-BS2:SER721.O 65.85%
CS2:ALA879.N-CS2:SER875.O 65.85%
CS1:TYR269.OH-CS1:PRO85.O 68.29%
BS2:MET697.N-BS1:GLY669.O 65.85%
CS2:LEU938.N-CS2:ILE934.O 65.85%
CS2:THR716.OG1-CS2:GLN1071.O 65.85%
AS1:VAL362.N-AS1:ASN334.O 65.85%
BS2:ILE693.N-BS1:SER673.O 65.85%
BS1:LEU611.N-BS1:SER596.O 65.85%
AS2:GLU918.N-AS2:ASN914.O 65.85%
CS1:LEU611.N-CS1:SER596.O 65.85%
BS1:LYS202.N-BS1:LYS195.O 65.85%
BS1:LEU277.N-BS1:HSE49.O 65.85%
BS1:VAL551.N-BS1:THR588.O 65.85%
CS1:VAL511.N-CS1:ILE434.O 65.85%
BS1:TYR91.N-BS1:GLY268.O 65.85%
AS1:TYR37.OH-AS1:LEU54.O 65.85%
BS1:ARG509.NH2-BS1:ASP442.OD2 65.85%
BS2:THR1238.OG1-BS2:LEU1234.O 63.41%
BS1:PHE194.N-BS1:VAL90.O 65.85%
CS2:SER1051.OG-CS2:HSE1064.ND1 65.85%
BS2:TYR1067.N-BS2:TYR1047.O 63.41%
BS1:ILE128.N-BS1:TYR170.O 65.85%
CS2:HSE1064.N-CS2:THR723.O 65.85%
BS2:ALA879.N-BS2:SER875.O 63.41%
BS1:PHE106.N-BS1:LEU117.O 65.85%
(continued)
388
10 Spike (S) Glycoprotein N165A and N234A Mutant
Table 10.7 (continued) Replica 4
Replica 5
Replica 6
AS1:ILE587.N-AS1:ASP574.O 65.85%
BS1:TYR313.N-BS1:VAL597.O 63.41%
CS1:ARG457.NH2-CS1:ASP467.OD1 65.85%
CS1:PHE92.N-CS1:PHE192.O 65.85%
AS2:ASN960.N-AS2:ALA956.O 63.41%
BS1:ARG246.NH2-BS1:ASP80.OD2 65.85%
CS1:LEU277.N-CS1:HSE49.O 65.85%
CS1:LEU611.N-CS1:SER596.O 63.41%
AS1:ARG158.NE-AS1:GLU156.OE1 65.85%
AS1:TYR451.OH-AS1:ASP442.OD2 65.85%
AS1:VAL551.N-AS1:THR588.O 63.41%
AS2:VAL729.N-AS2:HSD1058.O 65.85%
BS2:THR1077.OG1-BS2:PHE1095.O 63.41%
BS1:ASP568.N-BS1:THR572.O 63.41%
CS2:GLN957.N-CS2:ASN953.O 65.85%
CS2:MET902.N-CS2:PHE898.O 63.41%
AS1:PHE543.N-AS1:LEU546.O 63.41%
CS1:ILE598.N-CS1:ALA609.O 65.85%
CS2:GLU1031.N-CS2:THR1027.O 63.41%
CS1:LYS202.N-CS1:LYS195.O 63.41%
AS1:GLN271.N-AS1:PHE55.O 65.85%
AS1:PHE643.N-AS1:LEU650.O 63.41%
AS1:THR523.OG1-AS1:THR393.O 63.41%
BS1:VAL511.N-BS1:ILE434.O 65.85%
BS1:TYR37.OH-BS1:LEU54.O 63.41%
AS1:LEU118.N-AS1:LYS129.O 63.41%
CS1:ILE434.N-CS1:VAL511.O 65.85%
CS1:TYR37.OH-CS1:LEU54.O 63.41%
BS1:VAL512.N-BS1:ASP398.O 63.41%
AS2:LEU1218.N-AS2:TRP1214.O 63.41%
AS1:LEU229.N-AS1:PHE201.O 63.41%
BS1:ARG457.N-BS1:ASP420.OD1 63.41%
AS2:ILE1216.N-AS2:LYS1211.O 63.41%
AS1:VAL127.N-AS1:VAL120.O 63.41%
AS1:ILE434.N-AS1:VAL511.O 63.41%
CS2:ASN1173.N-CS2:ILE1169.O 63.41%
AS1:LEU118.N-AS1:LYS129.O 63.41%
AS2:VAL1096.N-AS2:PHE1103.O 63.41%
BS2:THR883.OG1-BS2:ALA879.O 63.41%
AS1:ILE358.N-AS1:VAL395.O 63.41%
AS2:THR1066.N-AS2:SER721.O 63.41%
AS2:SER1051.OG-AS2:HSE1064.ND1 63.41%
CS1:ILE358.N-CS1:VAL395.O 63.41%
BS2:VAL729.N-BS2:HSD1058.O 63.41%
BS2:ALA1026.N-BS2:ALA1022.O 63.41%
CS1:ALA397.N-CS1:LYS356.O 63.41%
AS1:LEU585.N-AS1:VAL576.O 63.41%
BS1:SER673.OG-BS1:ASP663.OD2 63.41%
CS1:GLN493.N-CS1:TYR453.O 63.41%
CS1:LEU277.N-CS1:HSE49.O 63.41%
AS2:LYS733.NZ-AS2:ASP775.OD2 63.41%
CS2:ASN928.N-CS2:ALA924.O 63.41%
BS1:TYR396.N-BS1:SER514.O 63.41%
CS1:VAL597.N-CS1:TYR313.O 63.41%
AS2:ASN777.N-AS2:GLU773.O 63.41%
AS1:THR572.OG1-BS2:ASP848.OD2 63.41%
CS1:TRP64.N-CS1:ALA27.O 63.41%
AS1:PHE59.N-AS1:PHE32.O 63.41%
AS2:GLN1005.N-AS2:LEU1001.O 63.41%
BS1:ALA363.N-BS1:CYS525.O 63.41%
CS1:ASP578.N-CS1:GLU583.O 63.41%
CS2:THR1077.OG1-CS2:PHE1095.O 60.98%
BS1:LEU244.N-BS1:PRO139.O 63.41%
AS2:THR883.OG1-AS2:ALA879.O 63.41%
CS2:THR1105.OG1-CS2:GLN1106.O 60.98%
BS1:ARG78.NH2-BS1:ASP80.OD1 63.41%
CS2:SER1055.OG-CS2:GLU819.OE1 63.41%
CS2:SER1037.OG-CS2:GLU1031.OE1 60.98%
BS1:ARG78.NE-BS1:ASP80.OD2 63.41%
CS1:LYS202.N-CS1:LYS195.O 63.41%
BS2:GLN1054.N-BS2:VAL1061.O 60.98%
AS1:LEU513.N-AS1:CYS432.O 63.41%
AS2:ASN1023.N-AS2:ARG1019.O 63.41%
AS2:VAL729.N-AS2:HSD1058.O 60.98%
AS2:THR1231.OG1-AS2:ILE1227.O 63.41%
CS2:THR1231.OG1-CS2:ILE1227.O 60.98%
BS1:ILE598.N-BS1:ALA609.O 60.98%
AS2:THR1066.N-AS2:SER721.O 63.41%
CS2:THR1077.OG1-CS2:PHE1095.O 60.98%
CS1:TYR313.OH-CS1:GLU309.O 60.98%
AS2:ASN777.N-AS2:GLU773.O 63.41%
CS2:THR791.OG1-CS2:PRO807.O 60.98%
AS1:VAL62.N-AS1:THR29.O 60.98%
BS2:VAL1008.N-BS2:LEU1004.O 63.41%
BS1:ILE651.N-BS1:VAL610.O 60.98%
BS1:VAL539.N-BS1:GLY550.O 60.98%
BS1:ARG509.NH2-BS1:ASP442.OD1 63.41%
BS2:ARG1000.NH1-BS2:ILE742.O 60.98%
CS1:VAL62.N-CS1:THR29.O 60.98%
AS1:THR208.N-AS1:LEU189.O 63.41%
AS1:TYR37.OH-AS1:LEU54.O 60.98%
BS1:PHE92.N-BS1:PHE192.O 60.98%
BS1:LEU585.N-BS1:VAL576.O 63.41%
AS1:PHE92.N-AS1:PHE192.O 60.98%
CS1:PHE194.N-CS1:VAL90.O 60.98%
AS2:THR883.OG1-AS2:ALA879.O 63.41%
AS1:LEU84.N-AS1:PHE238.O 60.98%
AS1:LEU229.N-AS1:PHE201.O 60.98%
BS1:ILE434.N-BS1:VAL511.O 63.41%
BS2:THR1027.OG1-BS2:ASN1023.O 60.98%
AS1:TYR380.N-AS1:GLY431.O 60.98%
AS2:PHE1075.N-AS2:ILE712.O 60.98%
AS1:VAL551.N-AS1:THR588.O 60.98%
AS1:TYR495.OH-AS1:VAL401.O 60.98%
CS2:THR1066.N-CS2:SER721.O 60.98%
BS1:TYR91.N-BS1:GLY268.O 60.98%
AS2:THR716.OG1-AS2:GLN1071.O 60.98%
AS2:GLU1031.N-AS2:THR1027.O 60.98%
CS1:TYR266.N-CS1:ALA93.O 60.98%
CS2:SER1051.OG-CS2:HSE1064.ND1 60.98%
BS2:LEU1063.N-BS2:PHE1052.O 60.98%
BS1:TYR380.N-BS1:GLY431.O 60.98%
CS2:GLN1011.N-CS2:TYR1007.O 60.98%
AS2:LEU938.N-AS2:ILE934.O 60.98%
CS1:ASN121.N-CS1:SER155.O 60.98%
CS1:TYR37.OH-CS1:LEU54.O 60.98%
BS2:ASN777.N-BS2:GLU773.O 60.98%
BS1:GLN493.N-BS1:TYR453.O 60.98%
CS1:TYR269.OH-CS1:PRO85.O 60.98%
AS1:LEU611.N-AS1:SER596.O 60.98%
CS2:THR1066.OG1-CS2:LYS1045.O 60.98%
BS2:THR1231.OG1-BS2:ILE1227.O 60.98%
AS1:VAL610.N-AS1:ILE651.O 60.98%
BS2:ASP737.N-BS2:GLY857.O 60.98%
BS2:VAL1068.N-BS2:THR719.O 60.98%
CS1:SER596.N-CS1:LEU611.O 60.98%
AS2:ASN928.N-AS2:ALA924.O 60.98%
AS2:LEU822.N-AS2:ILE818.O 60.98%
BS1:ARG319.NH1-BS1:ASN317.OD1, CS1:VAL551.N-CS1:THR588.O 60.98%
AS2:SER1051.OG-AS2:HSE1064.ND1 60.98%
CS2:ARG847.NH1-BS1:ASP568.OD2 60.98%
AS1:ARG273.N-AS1:ASP53.O, CS1:PHE543.N-CS1:LEU546.O 60.98%
BS1:VAL130.N-BS1:PHE168.O 60.98%
CS1:VAL551.N-CS1:THR588.O 60.98%
AS1:ILE128.N-AS1:TYR170.O, BS1:CYS336.N-BS1:VAL362.O 60.98%
BS1:PHE65.N-BS1:TYR265.O 60.98%
BS1:LYS202.N-BS1:LYS195.O 60.98%
CS1:ARG454.N-CS1:ASN422.OD1, BS1:SER443.OG-BS1:TYR495.O 60.98%
AS1:ARG44.NH2-AS1:ASP40.OD1 60.98%
AS1:ARG509.NE-AS1:ASP442.OD1 60.98%
AS2:THR1077.OG1-AS2:PHE1095.O, BS1:CYS649.N-BS1:TYR612.O 60.98%
BS2:CYS1082.N-BS2:VAL1133.O 60.98%
AS1:PHE58.N-AS1:ASP290.OD1, CS1:TYR279.N-CS1:VAL47.O 60.98%
BS1:LEU585.N-BS1:VAL576.O 60.98%
BS1:TYR91.N-BS1:GLY268.O, CS2:ASP1153.N-CS2:PHE1148.O 60.98%
BS1:ARG328.NE-BS1:ASP578.OD1 60.98%
AS2:TYR695.OH-AS1:SER673.O, AS2:CYS760.N-AS2:TYR756.O 60.98%
BS1:VAL511.N-BS1:ILE434.O 60.98%
AS1:PHE106.N-AS1:LEU117.O, AS1:SER438.OG-AS1:ASP442.OD1 60.98%
CS1:ARG355.NE-CS1:ASP398.OD2 60.98%
BS1:LEU118.N-BS1:LYS129.O, AS1:PHE347.N-AS1:ASP442.OD2 60.98%
Supplementary Information
389
Table 10.8 The 20 SBs (Sect. 7.3.2) of the wild-type from the analyses of the 175 ns’ continuous MD trajectory of SARS-CoV-2 glycosylated spike opening [339] ASP820-ARG815
A:ASP820-A:ARG815, B:ASP820-B:ARG815, C:ASP820-C:ARG815
ASP820-LYS811
A:ASP820-A:LYS811, C:ASP820-C:LYS811
ASP578-ARG328
A:ASP578-A:ARG328, B:ASP578-B:ARG328, C:ASP578-C:ARG328
ASP467-ARG454
A:ASP467-A:ARG454, C:ASP467-C:ARG454 C:ASP467-C:LYS458
ASP53-LYS195
A:ASP53-A:LYS195, B:ASP53-B:LYS195, C:ASP53-C:LYS195
ASP663-LYS310
A:ASP663-A:LYS310, B:ASP663-B:LYS310, C:ASP663-C:LYS310 B:ASP663-B:ARG683 B:ASP663-B:ARG685
GLU583-LYS535
A:GLU583-A:LYS535, B:GLU583-B:LYS535, C:GLU583-C:LYS535 A:GLU583-A:ARG328 A:GLU583-A:LYS558, C:GLU583-C:LYS558
ASP775-LYS733
A:ASP775-A:LYS733, B:ASP775-B:LYS733, C:ASP775-C:LYS733
GLU773-ARG1019
A:GLU773-A:ARG1019, B:GLU773-B:ARG1019 B:GLU773-B:LYS776, C:GLU773-C:LYS776 B:GLU773-A:LYS947
GLU340-LYS356
A:GLU340-A:LYS356, B:GLU340-B:LYS356, C:GLU340-C:LYS356
ASP574-LYS557
A:ASP574-A:LYS557, B:ASP574-B:LYS557, C:ASP574-C:LYS557 A:ASP574-B:LYS854, B:ASP574-C:LYS854, C:ASP574-A:LYS854 C:ASP574-A:ARG847
ASP40-ARG44
A:ASP40-A:ARG44, B:ASP40-B:ARG44, C:ASP40-C:ARG44
GLU725-HIS1064
A:GLU725-A:LYS1028, B:GLU725-B:LYS1028, C:GLU725-C:LYS1028
ASP1084-LYS1086
A:ASP1084-A:LYS1086, B:ASP1084-B:LYS1086, C:ASP1084-C:LYS1086
ASP571-ARG567
A:ASP571-A:ARG567, B:ASP571-B:ARG567 B:ASP571-C:LYS964 C:ASP571-A:ARG44
ASP405-ARG403
A:ASP405-A:ARG408, B:ASP405-B:ARG408, B:ASP405-C:ARG408, C:ASP405-A:ARG408 A:ASP405-A:LYS417 B:ASP405-C:LYS378
GLU465-ARG457
A:GLU465-A:LYS462, B:GLU465-B:LYS462, C:GLU465-C:LYS462
GLU191-ARG34
A:GLU191-A:ARG34, B:GLU191-B:ARG34, C:GLU191-C:ARG34
GLU1031-ARG1039
A:GLU1031-A:ARG1039, B:GLU1031-B:ARG1039, C:GLU1031-C:ARG1039 A:GLU1031-C:ARG1039, C:GLU1031-A:ARG1039, B:GLU1031-A:ARG1039, C:GLU1031-B:ARG1039
ASP405-ARG403
A:ASP405-A:ARG408, B:ASP405-B:ARG408, B:ASP405-C:ARG408, C:ASP405-A:ARG408 A:ASP405-A:LYS417 B:ASP405-C:LYS378
ASP574-LYS854
A:ASP574-B:LYS854, B:ASP574-C:LYS854, C:ASP574-A:LYS854
ASP442-ARG509
A:ASP442-A:ARG509, B:ASP442-B:ARG509, C:ASP442-C:ARG509 B:ASP442-B:ARG346, C:ASP442-C:ARG346
ASP398-ARG355
A:ASP398-A:ARG355, B:ASP398-B:ARG355, C:ASP398-C:ARG355
CS1:LYS558.NZ-CS1:GLU583.OE1 10.40%
AS2:LYS733.NZ-AS2:ASP775.OD2 24.86%, AS2:LYS733.NZ-AS2:ASP775.OD1 20.81%,
GLU583-LYS558
ASP775-LYS733
CS2:LYS776.NZ-CS2:GLU773.OE2 10.40%
BS1:LYS356.NZ-BS1:GLU340.OE1 17.34%
AS2:LYS854.NZ-CS1:ASP574.OD1 16.76%, BS2:LYS854.NZ-AS1:ASP574.OD2 39.31%
AS2:ARG847.NH2-CS1:ASP574.OD2 12.72%
AS1:ARG44.NH2-AS1:ASP40.OD1 67.05%, AS1:ARG44.NH1-AS1:ASP40.OD2 56.65%, AS1:ARG44.NH2-AS1:ASP40.OD2 11.56%, AS1:ARG44.NH1-AS1:ASP40.OD1 10.98%
GLU773-LYS776
GLU340-LYS356
ASP574-LYS854
ASP574-ARG847
ASP40-ARG44
CS1:ARG44.NH2-CS1:ASP40.OD2 77.46%, CS1:ARG44.NH1-CS1:ASP40.OD1 56.07%
BS1:ARG44.NH2-BS1:ASP40.OD2 74.57%, BS1:ARG44.NH1-BS1:ASP40.OD1 60.12%,
AS2:ARG1019.NE-AS2:GLU773.OE2 34.68%, AS2:ARG1019.NH2-AS2:GLU773.OE1 32.95%, AS2:ARG1019.NE-AS2:GLU773.OE1 30.64%, AS2:ARG1019.NH2-AS2:GLU773.OE2 26.01%
GLU773-ARG1019
CS2:LYS733.NZ-CS2:ASP775.OD2 40.46%, CS2:LYS733.NZ-CS2:ASP775.OD1 10.40%
BS2:LYS733.NZ-BS2:ASP775.OD1 32.95%, BS2:LYS733.NZ-BS2:ASP775.OD2 19.65%,
BS1:ARG683.NH2-BS1:ASP663.OD2 15.03%, BS1:ARG683.NH1-BS1:ASP663.OD1 13.87%
ASP663-ARG683
CS1:LYS310.NZ-CS1:ASP663.OD2 43.93%
BS1:LYS310.NZ-BS1:ASP663.OD2 18.50%, BS1:LYS310.NZ-BS1:ASP663.OD1 10.40%,
AS1:LYS310.NZ-AS1:ASP663.OD1 20.23%, AS1:LYS310.NZ-AS1:ASP663.OD2 18.50%,
CS1:LYS195.NZ-CS1:ASP53.OD1 16.18%, CS1:LYS195.NZ-CS1:ASP53.OD2 12.72%
BS1:LYS195.NZ-BS1:ASP53.OD1 13.29%,
AS1:LYS195.NZ-AS1:ASP53.OD1 15.03%,
ASP663-LYS310
CS1:LYS458.NZ-CS1:ASP467.OD2 31.79%, CS1:LYS458.NZ-CS1:ASP467.OD1 22.54%
ASP53-LYS195
CS1:ARG454.NH1-CS1:ASP467.OD1 42.20%
AS1:ARG454.NH2-AS1:ASP467.OD2 21.97%, AS1:ARG454.NH2-AS1:ASP467.OD1 17.92%, AS1:ARG454.NH1-AS1:ASP467.OD2 16.18%, AS1:ARG454.NH1-AS1:ASP467.OD1 15.03%
CS1:ARG328.NH1-CS1:ASP578.OD2 27.75%, CS1:ARG328.NH1-CS1:ASP578.OD1 24.86%, CS1:ARG328.NH2-CS1:ASP578.OD1 11.56%
ASP467-LYS458
ASP467-ARG454
BS1:ARG328.NH1-BS1:ASP578.OD2 26.01%, BS1:ARG328.NH1-BS1:ASP578.OD1 31.21%,
AS1:ARG328.NH1-AS1:ASP578.OD2 34.68%, AS1:ARG328.NH1-AS1:ASP578.OD1 16.18%,
CS2:ARG815.NE-CS2:ASP820.OD1 16.76%, CS2:ARG815.NE-CS2:ASP820.OD2 13.29%, CS2:ARG815.NH2-CS2:ASP820.OD1 10.40%
BS2:ARG815.NE-BS2:ASP820.OD1 34.10%, BS2:ARG815.NE-BS2:ASP820.OD2 23.70%,
AS2:ARG815.NH1-AS2:ASP820.OD2 12.14%,
ASP820-ARG815
ASP578-ARG328
HBs of the SB
SB
Table 10.9 HBs of the 20 SBs (Sect. 7.3.2) of the wild-type from the analyses of the 175 ns’ continuous MD trajectory of SARS-CoV-2 glycosylated spike (where AS1 is (chain A, 16–685), AS2 is (chain A, 686–1140), BS1 is (chain B, 16–685), BS2 is (chain B, 686–1140), CS1 is (chain C, 16–685), and CS2 is (chain C, 686–1140)) opening [339]
390 10 Spike (S) Glycoprotein N165A and N234A Mutant
AS1:ARG509.NE-AS1:ASP442.OD2 78.03%, AS1:ARG509.NH2-AS1:ASP442.OD1 49.13%,
ASP398-ARG355
AS2:LYS854.NZ-CS1:ASP574.OD1 16.76%, BS2:LYS854.NZ-AS1:ASP574.OD2 39.31%
ASP442-ARG509
CS1:ARG355.NH1-CS1:ASP398.OD2 25.43%, CS1:ARG355.NH1-CS1:ASP398.OD1 17.92%, CS1:ARG355.NH2-CS1:ASP398.OD1 14.45%, CS1:ARG355.NH2-CS1:ASP398.OD2 12.72%
BS1:ARG355.NH1-BS1:ASP398.OD2 41.04%, BS1:ARG355.NH1-BS1:ASP398.OD1 35.84%,
AS1:ARG355.NH1-AS1:ASP398.OD2 69.94%, AS1:ARG355.NH1-AS1:ASP398.OD1 10.40%,
CS1:ARG509.NE-CS1:ASP442.OD2 75.72%, CS1:ARG509.NH2-CS1:ASP442.OD1 60.12%
BS1:ARG509.NE-BS1:ASP442.OD1 50.87%, BS1:ARG509.NH2-BS1:ASP442.OD2 36.99%, BS1:ARG509.NH2-BS1:ASP442.OD1 14.45%, BS1:ARG509.NE-BS1:ASP442.OD2 13.87%,
AS1:LYS417.NZ-AS1:ASP405.OD2 23.12%, AS1:LYS417.NZ-AS1:ASP405.OD1 11.56%
ASP574-LYS854
CS1:ARG408.NH1-BS1:ASP405.OD2 17.34%, CS1:ARG408.NH2-BS1:ASP405.OD1 15.03%, CS1:ARG408.NH1-BS1:ASP405.OD1 14.45%, CS1:ARG408.NE-BS1:ASP405.OD2 10.98%
AS1:ARG408.NH1-CS1:ASP405.OD1 13.29%
AS1:ARG408.NH2-AS1:ASP405.OD1 25.43%, AS1:ARG408.NH2-AS1:ASP405.OD2 14.45%,
CS2:ARG1039.NE-AS2:GLU1031.OE1 24.28%, CS2:ARG1039.NE-AS2:GLU1031.OE2 13.29%
AS2:ARG1039.NH2-CS2:GLU1031.OE1 30.06%, AS2:ARG1039.NH2-CS2:GLU1031.OE2 21.39%,
AS2:ARG1039.NE-BS2:GLU1031.OE2 23.12%, AS2:ARG1039.NH2-BS2:GLU1031.OE2 20.81%,
CS2:ARG1039.NH1-CS2:GLU1031.OE1 15.61%,
BS2:ARG1039.NE-BS2:GLU1031.OE1 82.66%, BS2:ARG1039.NH2-BS2:GLU1031.OE2 52.60%,
AS2:ARG1039.NH1-AS2:GLU1031.OE2 12.72%,
CS1:ARG34.NH1-CS1:GLU191.OE1 38.73%
ASP405-LYS417
ASP405-ARG408
GLU1031-ARG1039
AS1:ARG34.NH1-AS1:GLU191.OE2 35.84%,
BS1:ARG34.NE-BS1:GLU191.OE1 79.19%, BS1:ARG34.NH2-BS1:GLU191.OE2 76.88%,
AS1:LYS417.NZ-AS1:ASP405.OD2 23.12%, AS1:LYS417.NZ-AS1:ASP405.OD1 11.56%
GLU191-ARG34
CS1:ARG567.NH1-CS1:ASP571.O 14.45%
AS1:ARG567.NH1-AS1:ASP571.O 23.70%,
CS2:LYS1028.NZ-CS2:GLU725.OE2 21.39%, CS2:LYS1028.NZ-CS2:GLU725.OE1 16.18%
BS2:LYS1028.NZ-BS2:GLU725.OE2 21.97%, BS2:LYS1028.NZ-BS2:GLU725.OE1 15.03%,
AS2:LYS1028.NZ-AS2:GLU725.OE2 29.48%, AS2:LYS1028.NZ-AS2:GLU725.OE1 23.12%,
ASP405-LYS417
ASP571-ARG567
GLU725-LYS1028
Supplementary Information 391
392 Table 10.10 The HBs with more than 66% occupancy rates of the wild-type from the analyses of the 175 ns’ continuous MD trajectory of SARS-CoV-2 glycosylated spike (where AS1 is (chain A, 16–685), AS2 is (chain A, 686–1140), BS1 is (chain B, 16–685), BS2 is (chain B, 686–1140), CS1 is (chain C, 16–685), and CS2 is (chain C, 686–1140)) opening [339]
10 Spike (S) Glycoprotein N165A and N234A Mutant HBs: BS2:ARG1039.NE-BS2:GLU1031.OE1 82.66% AS1:SER366.OG-AS1:ASP364.OD1 80.35% BS1:ARG34.NE-BS1:GLU191.OE1 79.19% AS1:ARG509.NE-AS1:ASP442.OD2 78.03% CS1:ARG44.NH2-CS1:ASP40.OD2 77.46% BS1:ARG34.NH2-BS1:GLU191.OE2 76.88% BS1:THR393.OG1-BS1:GLU516.OE1 76.88% BS1:TYR37.OH-BS1:LEU54.O 76.30% CS1:ILE101.N-CS1:GLU96.OE1 76.30% CS1:ILE100.N-CS1:GLU96.OE1 76.30% AS2:SER1051.OG-AS2:HSE1064.ND1 75.72% AS1:LEU229.N-AS1:PHE201.O 75.72% CS1:ARG509.NE-CS1:ASP442.OD2 75.72% BS2:SER1051.OG-BS2:HSE1064.ND1 75.14% BS1:TYR396.OH-BS1:GLU516.OE2 75.14% BS1:ARG44.NH2-BS1:ASP40.OD2 74.57% AS1:TYR37.OH-AS1:LEU54.O 74.57% CS1:LEU611.N-CS1:SER596.O 74.57% AS1:LEU611.N-AS1:SER596.O 73.99% CS1:TYR37.OH-CS1:LEU54.O 73.99% CS1:SER438.OG-CS1:ASP442.OD2 73.99% AS2:THR883.OG1-AS2:ALA879.O 73.41% AS1:SER221.OG-AS1:GLU191.OE1 72.83% BS1:TYR91.N-BS1:GLY268.O 72.25% CS1:TYR451.OH-CS1:ASP442.OD1 72.25% AS2:ASN777.N-AS2:GLU773.O 72.25% BS2:THR883.OG1-BS2:ALA879.O 72.25% CS1:SER673.OG-CS1:ASP663.OD1 71.68% CS1:ILE598.N-CS1:ALA609.O 71.68% BS1:VAL511.N-BS1:ILE434.O 71.68% AS2:THR1066.OG1-AS2:LYS1045.O 71.10% BS1:LEU611.N-BS1:SER596.O 70.52% BS1:LEU277.N-BS1:HSE49.O 70.52% CS1:LEU277.N-CS1:HSE49.O 70.52% BS1:LEU585.N-BS1:VAL576.O 70.52% AS1:ARG190.NE-AS1:GLU96.OE1 70.52% BS1:ILE651.N-BS1:VAL610.O 70.52% AS1:VAL511.N-AS1:ILE434.O 70.52% BS1:PHE106.N-BS1:LEU117.O 69.94% AS1:ARG355.NH1-AS1:ASP398.OD2 69.94% BS2:TYR695.OH-BS1:GLU661.O 69.94% BS1:ILE598.N-BS1:ALA609.O 69.94% CS1:TYR91.N-CS1:GLY268.O 69.94% CS2:TYR695.OH-CS1:GLU661.O 69.36% AS1:ILE651.N-AS1:VAL610.O 69.36% BS1:LEU242.N-BS1:PRO139.O 69.36% AS1:TYR91.N-AS1:GLY268.O 68.79% AS1:LYS202.N-AS1:LYS195.O 68.79% CS1:VAL512.N-CS1:ASP398.O 68.79% AS1:LEU585.N-AS1:VAL576.O 68.21% BS1:THR114.OG1-BS1:ASP111.OD1 68.21% CS1:TRP64.N-CS1:ALA27.O 68.21% CS1:VAL511.N-CS1:ILE434.O 68.21% AS1:ILE598.N-AS1:ALA609.O 67.63% BS2:THR1077.OG1-BS2:PHE1095.O67.05% CS1:ILE651.N-CS1:VAL610.O 67.05% AS1:ARG44.NH2-AS1:ASP40.OD1 67.05% AS1:ILE434.N-AS1:VAL511.O 67.05% BS1:VAL512.N-BS1:ASP398.O 67.05% AS1:TYR508.N-AS1:ILE402.O 67.05% AS2:GLU918.N-AS2:ASN914.O 66.47% BS2:SER1037.OG-BS2:GLU1031.OE1 66.47% CS1:LYS202.N-CS1:LYS195.O 66.47% CS1:LEU118.N-CS1:LYS129.O 66.47% BS1:ASN121.N-BS1:ARG102.O66.47% AS2:VAL1096.N-AS2:PHE1103.O 66.47%
Chapter 11
SARS (SARS-CoV-1)
Abstract Coronavirus SARS-CoV-2 spike (S) glycoproteins promote entry into cells and are the main target of antibodies and inhibitors. Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for SARS-CoV-2 and is an antiviral drug target against SARS-CoV-2. In Chap. 7, we found a strong polar contact LYS417ASP30 between the receptor-binding domain (RBD) of SARS-CoV-2 S and the human ACE2, keeping during 10 .μs of molecular dynamics (MD) simulations. Is this polar contact “unique” for SARS-CoV-2 or “common” for all coronavirus (such as SARS, MERS, etc.)? This chapter is to answer this question. The answer is that the strong polar contact LYS417-ASP30 is uniquely existing during 10 .μs only for SARS-CoV-2, but not for all coronavirus—this might be an important clue against COVID-19. As by-products, we found a strong salt bridge (with weak hydrogen bonds) GLU329-ARG426 and a strong hydrogen bond ASP355.OD2-THR486.OG1 (with occupancy rate 64.01%) between human ACE2 and SARS-CoV-1 S RBD. Keywords CoV · SARS-CoV-2 S RBD · SARS-CoV-1 RBD · MERS RBD · Human ACE2 · Polar contact LYS417-ASP30
11.1 Introduction “Coronavirus” (CoV) is an umbrella term for a family virus that shares similar properties. Some coronaviruses have been behind concerning disease outbreaks, namely, SARS (i.e., SARS-CoV-1), MERS, and SARS-CoV-2. The SARS-CoV-2 “severe acute respiratory syndrome (SARS) coronavirus 2” is the disease at the center of our current global health crisis of COVID-19. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE2, is a type I integral membrane protein of 805 amino acids that contains 1 HEXXH + E zincbinding consensus sequence, and it has been implicated in the regulation of heart function and also as a functional receptor for coronavirus such as SARS and SARSCoV-2 [359]. SARS-CoV-2 and SARS recognize the same ACE2 in humans. The © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_11
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11 SARS (SARS-CoV-1)
structure of SARS RBD complexed with ACE2 is the one with PDB entry 2AJF. This brief chapter is to do molecular dynamics (MD) computations of this structure to confirm the polar contact LYS417-ASP30 is unique for SARS-CoV-2 or common for all coronavirus (such as SARS, MERS, etc.) too.
11.2 Materials and Methods The MD materials and methods can be seen from [321]: MD trajectory was initiated from ACE2 in complex with the RBD of spike protein from SARS-CoV-1 (PDB entry 2AJF). AE chains of 2AJF.pdb are used, where A chain aa SER19ASP615 is human ACE2 and E chain aa CYS323-GLU502 is RBD of SARS-CoV-1 S. “The simulations used the Amber ff99SB-ILDN force field for proteins, the CHARMM TIP3P model for water, and the generalized Amber force field for glycosylated asparagine. The C- and A- peptide termini, including those exposed due to missing loops in the published structural models, are capped with amide and acetyl groups respectively. The system was neutralized and salted with NaCl, with a final concentration of 0.15 M. The interval between frames is 1.2 ns. The simulations were conducted at 310 K in the NPT ensemble.” The MD trajectory can be downloaded under the Creative Commons Attribution 4.0 International Public License from [321], and the data ID is DESRES-ANTON-10875755 (2AJF.pdb). We denote the model as the 2AJF model. In the below, (i) firstly, AE chains of 2AJF.pdb will be optimized into a much more stable transition state—the hybrid strategy [405] of mathematical optimization’s neighboring different (local search) algorithms is used in the optimization; (ii) secondly, we will present some important structural bioinformatics from the structure optimized; and (iii) we then prove the structural bioinformatics of (ii) from the analyses of the MD data of [321]. The noncovalent interactions of hydrogen bonds (HBs), salt bridges (SBs), van der Waals (vdWs) contacts, and hydrophobic (HYD) interactions are driving a protein to be able to perform its biological functions. This chapter will find out the HBs, SBs, HYD interactions, and vdWs contacts of each model from the large MD trajectory data and evaluate the reliability of the MD trajectory data.
11.3 New Structural Bioinformatics We optimized the AE chains of 2AJF.pdb and got an optimized structure (denoted as 2AJF-AEchains-Optimized ) with 2.102410 Å of RMSD value from its original structure. For the 2AJF-AEchains-Optimized structure, we found 1 SB A:GLU329E:ARG426 between A chain and E chain, 2 SBs E:ASP429-E:ARG495 and E:ASP385-E:ARG342 in E chain, and 17 SBs in A chain, A:ASP201-A:ARG219, A:GLU208-A:ARG219, A:GLU37-A:ARG393, A:GLU457-A:ARG460, A:ASP509-A:LYS187,
11.3 New Structural Bioinformatics
395
A:GLU406-A:HIS374, A:ASP355-A:ARG357, A:ASP431-A:LYS288, A:GLU435-A:HIS540, A:GLU310-A:ARG306, A:GLU402-A:HIS378 (GLU402-HIS374), A:GLU435-A:LYS541, A:GLU402-A:HIS374, A:ASP597-A:LYS600, A:GLU182-A:ARG115 (here, GLU189LYS112 of Chap. 7 was replaced), A:GLU227-A:LYS458, and A:ASP543-A:HIS417 (here,
GLU495-ARG177 and GLU181-ARG177 of Chap. 7 were lost); 87 HBs; 10 π -cations E:LYS323.N-E:PHE325, E:TYR383-E:ARG342.NH2-E:PHE451, E:ARG453.NH2-
.
E:TRP340, A:ARG357.NH2-A:TYR48, A:ARG273.NH2-A:TYR515, A:ARG169.NH2A:TRP165, A:ARG204.NH2-A:TRP461 (2), and A:LYS174.NZ-A:TYR497; 28 .π -.π stackings E:TYR202-E:TYR196, E:PHE460-E:HIS445, E:TYR410-E:TRP340 (2), E:TYR484E:TYR41, E:TRP69-E:PHE40, A:TYR255-A:HIS265 (2), A:TRP459-A:TRP477-A:TRP478 (2), A:PHE504-A:HIS505-A:PHE512/A:TYR515, A:TYR48-A:TRP349 (2), A:TYR497-A:HIS493, A:PHE523-A:TYR587-A:PHE588, A:TYR385-A:TYR381, A:TYR217-A:TRP566, A:PHE400A:PHE525, A:PHE315-A:PHE314-A:HIS373-A:PHE369, A:PHE327-A:TRP328 (2), and A:TYR127-A:TRP168; and its Poison-Boltzmann electrostatic potential surface,
hydrophobic/hydrophilic surface, secondary structure, SASA, etc.; we know that E chain (i.e., RBD of spike) has high Psi degrees and low Phi degrees. For the 10 .μs MD simulation trajectory data [321], there are 8335 frames with frame interval 1.2 ns. From the 8335 frames, we got 189 SBs and 4696 HBs (we list the HBs with more than 50% occupancy rates during the 10 .μs’ MD simulations (Figs. 11.2 and 11.3) for the 2AJF-model in Table 11.6). We can confirm a strong polar contact E:ASP429-E:ARG495 in chain E (i.e., the RBD of spike) (Fig. 11.3) (HBs E:ARG495.NE-E:ASP429.OD2 is with 56.12% occupancy rate, and E:ARG495.NH2-E:ASP429.OD1 is with 51.34% occupancy rate); the strong SBs ASP431-LYS288 (with HBs LYS288.NZ-ASP431.OD2 (15.87%) and LYS288.NZ-ASP431.OD1 (15.60%)—where in the bracket are the HB occupancy rates), ASP509-LYS187 (with HBs LYS187.NZ-ASP509.OD1 (18.21%) and LYS187.NZ-ASP509.OD2 (12.86%)), GLU435-LYS541 (with HBs LYS541.NZ-GLU435.OE1 (12.97%) and LYS541.NZGLU435.OE2 (12.37%)), ASP201-ARG219 (with HBs ARG219.NE-ASP201.OD2 (26.55%), ARG219.NH2-ASP201.OD1 (23.78%), ARG219.NE-ASP201.OD1 (13.32%), ARG219.NH2ASP201.OD2 (10.39%), and ARG219.NE-ASP201.CG (0.05%)), GLU182-ARG115 (with HBs ARG115.NH1-GLU182.OE1 (22.27%), ARG115.NH1-GLU182.OE2 (21.55%), ARG115.NEGLU182.OE2 (20.02%), and ARG115.NE-GLU182.OE1 (19.53%)), ASP355-ARG357 (with HBs ARG357.NH1-ASP355.OD2 (64.24%) and ARG357.NE-ASP355.OD1 (57.47%)), ASP597LYS600 (with HBs LYS600.NZ-ASP597.OD1 (11.97%) and LYS600.NZ-ASP597.OD2 (11.66%)), and GLU227-LYS458 in chain A (i.e., human ACE2) (Fig. 11.3); and a
strong SB A:GLU329-E:ARG426 between chain A and chain E (but with weak HBs E:ARG426.NH2-A:GLU329.OE1 (6.42%), E:ARG426.NH2-A:GLU329.OE2 (6.23%), E:ARG426.NH1-A:GLU329.OE2 (4.27%), and E:ARG426.NH1-
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11 SARS (SARS-CoV-1)
A:GLU329.OE1 (4.01%)) of the 2AJF-AEchains-Optimized model; we illuminate some important SBs in Fig. 11.1, where we know the SB A:GLU329-E:ARG426 is very strong and A:GLU23-E:LYS465 and A:GLU37-E:LYS390 are very weak (HBs E:LYS465.NZ-A:GLU23.OE2, E:LYS465.NZ-A:GLU23.OE1, E:LYS390.NZA:GLU37.OE1, and E:LYS390.NZ-A:GLU37.OE2 are also very weak with low occupancy rates 0.17%, 0.13%, 0.32%, and 0.28%, respectively). In Chap. 7, we found at GLU329 of human ACE2, there is a very strong polar contact linking to the residue ARG439 of SARS-CoV-2 S RBD—where the structure of 6VW1.pdb was determined based on SARS’ template so that we found the polar contact GLU329-ARG439. At position 417 for SARS-CoV-1 is a strictly hydrophobic residue MET417 (2AJF.pdb). For SARS-CoV-1, we cannot find a strong polar contact at 417 of spike RBD linking to ASP30 of human ACE2.For MERS-CoV, its host binding to is the DPP4 receptor, not the ACE2; thus, here, we cannot do a comparison for the ACE2 between MERS-CoV-1 and SARS-CoV-2. For SARSCoV-1, from Table 11.6, we found a strong HB E:THR486.OG1-A:ASP355.OD2 with occupancy rate 64.01% during the whole 10 .μs of MD.
For the MD, during the 10 .μs starting from about the 2450th frame, RMSD values (Fig. 11.2) equilibrate around 4.2 Å, and the whole RMSD values of 8335 frames (whose frame interval is 1.2 ns) vary within about 2 Å—this implies to us the MD is very reliable; larger RMSF values (Fig. 11.2) are mainly at segments 129–139, 336–346, 371–381, and 461–471 and the C-terminal around residue 609. The secondary structure developments have no significant changes in 10 .μs, but the segments 77–82, 146–147, 171–175, 249–252, 275–281, 332–342, 422–431, 492–509, and 607–615 of human ACE2 and the segments 323–334, 345–358, 367– 382, and 418–501 of the spike have changes during the 10 .μs of MD (Figs. 11.4 and 11.2).
11.3 New Structural Bioinformatics
397
Fig. 11.1 Important SBs A:GLU329-E:ARG426, AGLU23-ELYS465, AGLU37-ELYS390, etc. of the 2AJF model between the SARS-CoV-1 spike and the human ACE2 confirmed by MD data in [321]
Fig. 11.2 The RMSD and RMSF performances of the MD of the 2AJF model for SARS-CoV-1
11.3.1 SARS-CoV-1 Spike in Folding@home We got the SARS-CoV-1 spike (trimer, 5x58.pdb) 741 .μs’ MD free data of Folding@home (https://foldingathome.org/) from website https://osf.io/fs2yv/file [439]. The spike trimer has AB chains (ARG18-ARG667, SER668-VAL1104), CD chains (ARG18-ARG667, SER668-VAL1104), and EF chains (ARG18ARG667, SER668-VAL1104). In the optimized AB chains, i.e., the spike monomer, we found .π -cations B:TRP868-B:ARG887.NH2+-B:TRP868, B:ARG1021.NH2+B:PHE1024-B:LYS1010.NZ+, A:ARG453.NH2+-A:TRP340, A:LYS221.NZ+-A:PHE193, A:PHE59-A:LYS188.NZ+-A:TYR195, A:ARG183.NH2+-A:HIS181, and A:ARG207.NH2+A:HIS70 and .π -.π stackings B:TRP868-B:TYR886-B:TRP868, B:TYR771-B:PHE870, B:PHE784-B:PHE779, B:PHE1034-B:PHE784-B:PHE880-B:PHE782-B:PHE909, A:TRP423A:PHE361-A:PHE329, A:TYR646-B:TYR677, A:TYR440-A:TYR481-A:PHE483, A:TRP340A:TYR410-A:TRP340, A:PHE89-A:TRP101-A:PHE185, A:HIS70-A:PHE253-A:HIS33, and A:PHE22-A:PHE76-A:TRP245. The optimized trimer has the following SBs:
◦ B:ASP1023-B:LYS1027, D:ASP1023-D:LYS1027, F:ASP1023-F:LYS1027 ◦ B:ASP1100-F:ARG1073, D:ASP1100-B:ARG1073, F:ASP1100-D:ARG1073
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11 SARS (SARS-CoV-1)
E:ASP134-E:ARG232 A:ASP171-A:LYS175, C:ASP171-C:LYS175, E:ASP171-E:LYS175 A:ASP191-A:LYS190, C:ASP191-C:LYS190, E:ASP191-E:LYS190 C:ASP267-C:LYS265 A:ASP277-A:ARG620, C:ASP277-C:ARG620, E:ASP277-E:ARG620 A:ASP376-A:LYS373, A:ASP376-A:LYS514, C:ASP376-C:LYS514, E:ASP376-E:LYS514 A:ASP385-A:ARG342, C:ASP385-C:ARG342, E:ASP385-E:ARG342 A:ASP392-A:ARG395, C:ASP392-C:LYS390, E:ASP392-E:ARG395, A:ASP393-A:LYS390, E:ASP393-E:LYS390 C:ASP407-C:LYS411, E:ASP407-E:LYS411, E:ASP407-E:LYS447 A:ASP414-A:LYS411 A:ASP415-C:LYS190, C:ASP415-E:LYS190, E:ASP415-A:LYS190 A:ASP429-A:ARG495, C:ASP429-C:ARG495, E:ASP429-E:ARG495 A:ASP44-A:ARG48, C:ASP44-C:ARG48, E:ASP44-E:ARG48 A:ASP454-A:ARG441, C:ASP454-C:ARG441, E:ASP454-E:ARG441, A:ASP454-A:ARG444, C:ASP454-C:ARG444, E:ASP454-E:ARG444 A:ASP463-A:LYS465, C:ASP463-C:LYS465, E:ASP463-E:LYS465 A:ASP480-A:LYS439, C:ASP480-C:LYS439, E:ASP480-E:LYS439 A:ASP50-A:LYS265, E:ASP50-E:LYS265 A:ASP554-D:LYS836, C:ASP554-F:LYS836, E:ASP554-B:LYS836 A:ASP557-D:ARG982, C:ASP557-F:ARG982, E:ASP557-B:ARG982 A:ASP560-A:LYS543, C:ASP560-C:LYS543, E:ASP560-E:LYS543, A:ASP560-D:LYS836 A:ASP57-A:LYS188, C:ASP57-C:LYS188, E:ASP57-E:LYS188 A:ASP649-A:LYS297, C:ASP649-C:LYS297, E:ASP649-E:LYS297 B:ASP757-B:ARG761, D:ASP757-D:ARG761, F:ASP757-F:ARG761 B:ASP790-B:LYS777, D:ASP790-D:LYS777, F:ASP790-F:LYS777 B:ASP802-B:ARG797 D:ASP802-D:LYS793, F:ASP802-F:LYS793 F:ASP812-F:LYS817 F:ASP825-F:ARG829 B:ASP830-B:ARG829, D:ASP830-D:ARG829 D:ASP849-D:ARG797, F:ASP849-F:ARG797 A:ASP85-A:LYS84, C:ASP85-A:ARG449, E:ASP85-C:ARG449 B:ASP850-B:LYS796, D:ASP850-D:ARG797, D:ASP850-D:LYS796, F:ASP850-F:ARG797, F:ASP850-F:LYS796 B:ASP932-B:LYS929, D:ASP932-D:LYS929, F:ASP932-F:LYS929 B:ASP961-B:ARG965, D:ASP961-D:ARG965, F:ASP961-F:ARG965 B:ASP976-F:ARG977, D:ASP976-B:ARG977, F:ASP976-D:ARG977 B:GLU1013-B:ARG1021, B:GLU1013-F:ARG1021, D:GLU1013-B:ARG1021, D:GLU1013-D:ARG1021, F:GLU1013-D:ARG1021, F:GLU1013-F:ARG1021 D:GLU1054-D:ARG1055 B:GLU1066-B:HIS1065, D:GLU1066-D:HIS1065, F:GLU1066-F:HIS1065 B:GLU1074-B:ARG1089, D:GLU1074-D:ARG1089, F:GLU1074-F:ARG1089
11.3 New Structural Bioinformatics
◦ ◦ .◦ .◦ .◦ .◦ .◦ .◦ .◦ .◦ .◦ . .
◦ ◦ .◦ .◦ .◦ .◦ . .
399
E:GLU162-E:ARG126 A:GLU174-A:LYS142, C:GLU174-C:LYS142, E:GLU174-E:LYS142 A:GLU184-A:ARG38, C:GLU184-C:ARG38, E:GLU184-E:ARG38 A:GLU268-E:ARG544, C:GLU268-A:ARG544, E:GLU268-C:ARG544 A:GLU294-A:LYS287, C:GLU294-C:LYS287, E:GLU294-E:LYS287 A:GLU327-A:LYS343, C:GLU327-C:LYS343, E:GLU327-E:LYS343 A:GLU502-C:LYS221, C:GLU502-E:LYS221, E:GLU502-A:LYS221 A:GLU593-A:ARG667 A:GLU640-F:LYS672 A:GLU647-D:LYS768, C:GLU647-F:LYS768, E:GLU647-B:LYS768 B:GLU707-B:LYS1010, D:GLU707-D:LYS1010, F:GLU707-F:LYS1010, F:GLU707-F:HIS1046 B:GLU730-B:LYS968, D:GLU730-D:LYS968, F:GLU730-F:LYS968 B:GLU755-B:ARG1001, D:GLU755-D:ARG1001, F:GLU755-F:ARG1001 B:GLU762-B:ARG758, F:GLU762-F:ARG758, F:GLU762-F:ARG761 B:GLU900-F:LYS1068, D:GLU900-B:LYS1068, F:GLU900-D:LYS1068 A:GLU93-A:ARG99, C:GLU93-C:ARG99, E:GLU93-E:ARG99 B:GLU999-D:ARG1001, D:GLU999-F:ARG1001, F:GLU999-B:ARG1001.
The HBs of MD of 5x58 SARS-CoV-1 spike trimer with occupancy rates .≥30% during the 741 .μs’ MD are listed in Tables 11.1 and 11.2.
11.3.2 HCoV-NL63 Spike in Folding@home SARS-CoV-1 caused an outbreak in 2003 with a high case fatality rate but has not become a pandemic. NL63 was discovered in the following year and continues to spread around the globe but is substantially less lethal than either SARS virus [381]. Human coronavirus 229E and OC43 are another two human coronaviruses. We got the HCoV-NL63 spike (trimer) 651 .μs’ MD free data of Folding@home (https://foldingathome.org/) from website https://osf.io/fs2yv/file [439]. The trimer has ABC chains; in each chain, there are 1202 residues ALA23PHE1224. In the optimized A chain, we get .π -cations ARG1204.NH2+-TYR1153, ARG1105.NH2+-PHE1108-LYS1094.NZ+, ARG870.NH2+-PHE878, ALA23.N+TYR204, LYS311.NZ+-PHE342, and LYS390.NZ+-TYR587 and .π -.π stackings PHE840-PHE835, PHE848-PHE950-TYR851, HIS71-TYR176, TYR893-
400
11 SARS (SARS-CoV-1)
TYR910, PHE230-TRP235, TYR298-PHE402-PHE142, PHE317-PHE384, TRP600-PHE552-TRP600, PHE560-TYR473, PHE493-TRP541-TRP585-HIS586, and TRP541-TRP585-TRP541. The optimized trimer has the following SBs: ◦ ◦ .◦ .◦ .◦ . .
◦ ◦ .◦ .◦ .◦ .◦ . .
◦ ◦ .◦ .◦ .◦ . .
◦ ◦ .◦ .◦ .◦ .◦ .◦ .◦ . .
◦
.
◦ ◦ .◦ .◦ . .
◦ ◦ .◦ .◦ .◦ . .
A:ASP1048-B:LYS629, B:ASP1048-C:LYS629, C:ASP1048-A:LYS629 A:ASP1051-B:LYS556, B:ASP1051-C:LYS556, C:ASP1051-A:LYS556 A:ASP1150-A:ARG1204, B:ASP1150-B:ARG1204, C:ASP1150-C:ARG1204 A:ASP1167-A:ARG1172, B:ASP1167-B:ARG1172, C:ASP1167-C:ARG1172 A:ASP1188-B:ARG1158, B:ASP1188-C:ARG1158, C:ASP1188-A:ARG1158, A:ASP1188-A:ARG1182, B:ASP1188-B:ARG1182, C:ASP1188-C:ARG1182 A:ASP125-A:LYS107, B:ASP125-B:LYS107, C:ASP125-C:LYS107 A:ASP223-A:ARG225, B:ASP223-B:ARG225, C:ASP223-C:ARG225 A:ASP393-A:LYS390, B:ASP393-B:LYS390, C:ASP393-C:LYS390 A:ASP411-A:LYS311, B:ASP411-B:LYS311, C:ASP411-C:LYS311 A:ASP422-A:ARG250, B:ASP422-B:ARG250, C:ASP422-C:ARG250 A:ASP439-A:ARG225, B:ASP439-B:ARG225, C:ASP439-C:ARG225, A:ASP439-A:ARG256, B:ASP439-B:ARG256, C:ASP439-C:ARG256 A:ASP466-C:ARG799, C:ASP466-B:ARG799 A:ASP484-A:ARG525, B:ASP484-B:ARG525, C:ASP484-C:ARG525 A:ASP634-A:LYS562, B:ASP634-B:LYS562, C:ASP634-C:LYS562 A:ASP682-A:ARG702, B:ASP682-B:ARG702, C:ASP682-C:ARG702 A:ASP816-A:ARG819, B:ASP816-B:ARG819, C:ASP816-C:ARG819, A:ASP816-A:LYS812, B:ASP816-B:LYS812, C:ASP816-C:LYS812 A:ASP828-A:ARG1088, B:ASP828-B:ARG1088, C:ASP828-C:ARG1088 A:ASP83-A:LYS167, B:ASP83-B:LYS167, C:ASP83-C:LYS167 A:ASP850-A:LYS973, B:ASP850-B:LYS973, C:ASP850-C:LYS973 B:ASP875-B:ARG870 A:ASP892-A:LYS894, B:ASP892-B:LYS894, C:ASP892-C:LYS894 C:ASP922-C:ARG925 A:GLU1002-A:ARG748, B:GLU1002-B:ARG748, C:GLU1002-C:ARG748 A:GLU1083-A:LYS1080, B:GLU1083-B:LYS1080, C:GLU1083-C:LYS1080, A:GLU1083-C:ARG1089 A:GLU1097-A:ARG1105, A:GLU1097-B:ARG1105, B:GLU1097-B: ARG1105, B:GLU1097-C:ARG1105, C:GLU1097-A:ARG1105, C:GLU1097C:ARG1105 A:GLU1223-A:LYS1219, B:GLU1223-B:LYS1219, C:GLU1223-C:LYS1219 A:GLU375-A:ARG297, B:GLU375-B:ARG297, C:GLU375-C:ARG297 A:GLU398-A:LYS318, B:GLU398-B:LYS318, C:GLU398-C:LYS318 A:GLU448-A:ARG250, B:GLU448-B:ARG250, C:GLU448-C:ARG250, A:GLU448-C:LYS801, B:GLU448-A:LYS801, C:GLU448-B:LYS801 A:GLU471-A:LYS629, B:GLU471-B:LYS629, C:GLU471-C:LYS629 A:GLU582-A:LYS546, B:GLU582-B:LYS546, C:GLU582-C:LYS546 A:GLU602-C:ARG1049, B:GLU602-A:ARG1049, C:GLU602-B:ARG1049 A:GLU618-A:ARG617, B:GLU618-B:ARG617, C:GLU618-C:ARG617 A:GLU700-A:ARG702, B:GLU700-B:ARG702, C:GLU700-C:ARG702
Supplementary Information
401
◦ A:GLU776-A:HIS1130, B:GLU776-B:HIS1130, C:GLU776-C:HIS1130, A:GLU776-A:LYS1094, B:GLU776-B:LYS1094, C:GLU776-C:LYS1094 .◦ A:GLU825-A:ARG1085, B:GLU825-B:ARG1085, C:GLU825-C:ARG1085, A:GLU825-A:ARG1088, B:GLU825-B:ARG1088, C:GLU825-C:ARG1088 .◦ A:GLU924-A:ARG746 .◦ A:GLU94-A:ARG72, B:GLU94-B:ARG72, C:GLU94-C:ARG72. .
The HBs of MD of HCoV-NL63 spike trimer with occupancy rates .≥30% during the 651 .μs’ MD are listed in Tables 11.3, 11.4, and 11.5.
11.4 Concluding Remarks In Chap. 7, we found a strong polar contact LYS417-ASP30 between the RBD of SARS-CoV-2 S and the human ACE2, keeping during 10 .μs of MD. Is this polar contact “unique” for SARS-CoV-2 or “common” for all coronavirus (such as SARS, MERS, etc.)? This chapter answered this question. The answer is: the strong polar contact LYS417-ASP30 is uniquely existing during 10 .μs only for SARS-CoV-2, but not for all coronavirus such as SARS and MERS. As by-products, we found a strong SB (with weak HBs) GLU329-ARG426 and a strong HB ASP355.OD2THR486.OG1 (with occupancy rate 64.01%) between the human ACE2 and the RBD of SARS-CoV-1 S (Table 11.6).
Supplementary Information
402
11 SARS (SARS-CoV-1)
Fig. 11.3 Some strong SBs of the 2AJF model confirmed by MD trajectory data in [321]
Supplementary Information
403
Fig. 11.4 The secondary structure developments of the MD of the 2AJF model for SARS-CoV-1 (where the frame interval is 12 ns)
404
Fig. 11.4 (continued)
11 SARS (SARS-CoV-1)
D:SER701.N-D:VAL1050.O 54.10%
B:SER703.N-B:THR1048.O 54.10%
F:GLN756.NE2-F:ILE752.O 54.10%
F:THR991.OG1-F:GLN987.O 54.10%
C:ILE573.N-C:ASP560.O 54.10%
A:VAL525.N-A:GLY536.O 54.10%
C:VAL124.N-C:ILE117.O 54.10%
D:VAL1076.N-D:THR1087.O 54.10%
F:VAL1076.N-F:THR1087.O 54.10%
C:ASP429.N-C:THR425.O 54.10%
F:GLU1013.N-F:THR1009.O 54.10%
D:THR921.OG1-D:GLN917.O 54.10%
D:THR988.OG1-D:GLN984.O 54.10%
E:TYR88.N-E:GLY255.O 54.10%
A:ILE115.N-A:ARG126.O 54.10%
D:VAL1078.N-D:PHE1085.O 52.46%
B:THR863.OG1-B:LEU859.O 52.46%
B:THR760.OG1-B:GLN756.O 52.46%
F:VAL675.N-E:SER659.O 52.46%
B:VAL675.N-A:SER659.O 52.46%
E:VAL290.N-E:LEU286.O 52.46%
A:ALA237.N-A:PHE138.O 52.46%
E:ALA237.N-E:PHE138.O 52.46%
C:TYR438.OH-C:ASP429.OD1 52.46%
E:ASP267.N-E:THR271.O 52.46%
A:GLY552.N-A:SER561.O 52.46%
E:VAL642.N-F:ALA676.O 52.46%
F:THR980.N-F:ASP976.O 52.46%
C:ALA237.N-C:PHE138.O 52.46%
A:ILE116.N-A:TRP101.O 52.46%
B:THR865.OG1-B:SER861.O 50.82%
B:GLU1013.N-B:THR1009.O 50.82%
D:MET770.N-B:ALA683.O 50.82%
B:SER798.N-B:GLU801.OE1 50.82%
E:LYS287.N-E:LEU283.O 50.82%
D:VAL945.N-D:LEU941.O 50.82%
D:ARG982.NH1-D:ILE724.O 50.82%
A:ASP564.N-A:GLU569.O 50.82%
E:ILE125.N-E:TYR163.O 50.82%
D:THR922.OG1-D:GLU918.O 50.82%
A:VAL497.N-A:LEU421.O 81.97%
F:VAL990.N-F:LEU986.O 80.33%
B:VAL1043.N-B:GLN1036.O 80.33%
F:VAL1043.N-F:GLN1036.O 73.77%
E:VAL124.N-E:ILE117.O 73.77%
E:VAL497.N-E:LEU421.O 73.77%
B:VAL860.N-B:THR856.O 72.13%
C:VAL254.N-C:THR67.O 72.13%
A:TYR41.OH-A:LEU58.O 70.49%
F:THR865.OG1-F:SER861.O 68.85%
F:VAL860.N-F:THR856.O 68.85%
F:THR856.OG1-F:GLU801.OE2 68.85%
A:ASP267.N-A:THR271.O 68.85%
A:VAL124.N-A:ILE117.O 68.85%
C:VAL498.N-C:ASP385.O 68.85%
C:VAL497.N-C:LEU421.O 68.85%
D:VAL1043.N-D:GLN1036.O 67.21%
E:VAL496.N-E:PHE387.O 67.21%
E:VAL254.N-E:THR67.O 67.21%
E:VAL498.N-E:ASP385.O 67.21%
F:SER798.N-F:GLU801.OE1 65.57%
D:VAL711.N-D:HIS1040.O 65.57%
B:VAL990.N-B:LEU986.O 65.57%
A:VAL537.N-A:SER574.O 65.57%
C:VAL537.N-C:SER574.O 65.57%
A:VAL102.N-A:ARG232.O 65.57%
A:VAL114.N-A:PHE103.O 65.57%
B:VAL1050.N-B:SER701.O 65.57%
D:VAL1050.N-D:SER701.O 65.57%
F:ILE979.N-F:ILE975.O 63.93%
B:VAL711.N-B:HIS1040.O 63.93%
D:VAL990.N-D:LEU986.O 63.93%
D:THR865.OG1-D:SER861.O 63.93%
F:GLN1018.NE2-F:HIS1030.O 62.30%
F:ALA1004.N-F:ILE1000.O 62.30%
D:ALA1004.N-D:ILE1000.O 62.30%
E:PHE47.N-C:PHE551.O 62.30%
A:VAL254.N-A:THR67.O 62.30%
E:VAL102.N-E:ARG232.O 62.30%
A:VAL498.N-A:ASP385.O 62.30%
A:SER279.OG-A:ASP277.OD2 44.26%
D:ILE1000.N-D:ARG996.O 44.26%
F:THR760.OG1-F:GLN756.O 44.26%
B:VAL1042.N-B:MET709.O 44.26%
C:SER113.N-C:CYS128.O 44.26%
A:ALA127.N-A:PHE161.O 44.26%
C:VAL420.N-C:LYS365.O 44.26%
C:LYS142.N-C:SER239.O 44.26%
E:ILE573.N-E:ASP560.O 44.26%
D:SER717.N-D:THR841.O 44.26%
F:ILE1000.N-F:ARG996.O 44.26%
B:TYR677.OH-A:GLU647.O 44.26%
D:THR856.OG1-D:GLU801.OE2 44.26%
D:GLU1013.N-D:THR1009.O 44.26%
B:SER1052.N-B:ASN699.O 44.26%
F:PHE1057.N-F:ILE694.O 44.26%
E:ASP429.N-E:THR425.O 45.90%
E:CYS635.N-E:GLN599.O 45.90%
F:TYR677.OH-E:GLU647.O 45.90%
A:PHE460.N-A:TYR475.O 45.90%
E:THR229.N-E:GLY104.O 45.90%
C:ILE116.N-C:TRP101.O 45.90%
C:LEU194.N-C:LEU222.O 45.90%
F:SER750.N-F:ASN746.O 45.90%
B:PHE1044.N-B:GLU707.O 45.90%
C:ASP385.N-C:VAL498.O 45.90%
A:CYS133.N-A:ILE152.O 45.90%
A:VAL140.N-A:ALA237.O 45.90%
A:LYS258.N-A:PHE59.O 45.90%
E:TYR88.OH-E:GLU184.OE2 45.90%
E:ASP572.N-E:THR539.O 45.90%
F:PHE1044.N-F:GLU707.O 45.90%
D:SER798.N-D:GLU801.OE1 45.90%
B:THR1048.N-B:SER703.O 45.90%
B:VAL1047.N-B:MET1032.O 45.90%
E:VAL66.N-E:HIS33.O 45.90%
A:PHE262.N-A:THR55.O 45.90%
C:THR608.OG1-C:THR604.O 45.90%
D:ALA1008.N-D:ALA1004.O 45.90%
B:TYR1049.N-B:TYR1029.O 45.90%
Table 11.1 The HBs of MD of 5x58 SARS-CoV-1 spike trimer with occupancy rates ≥30% during the 741 μs’ MD
(continued)
A:GLU93.N-A:HIS181.O 40.98%
C:PHE47.N-A:PHE551.O 40.98%
A:LEU571.N-A:VAL562.O 40.98%
B:THR980.N-B:ASP976.O 40.98%
D:THR991.OG1-D:GLN987.O 40.98%
D:ALA676.N-C:GLU640.O 40.98%
D:GLN931.N-D:LEU927.O 40.98%
F:VAL1042.N-F:MET709.O 40.98%
F:MET770.N-D:ALA683.O 40.98%
D:PHE909.N-D:ILE905.O 40.98%
D:PHE1085.N-D:VAL1078.O 40.98%
D:ILE1086.N-D:GLN1095.O 40.98%
C:ILE81.N-C:PHE231.O 42.62%
A:GLU184.N-A:GLY199.O 42.62%
E:SER607.OG-E:CYS603.O 42.62%
E:VAL314.N-E:ASN528.O 42.62%
A:ILE203.N-A:LYS180.O 42.62%
D:GLN984.N-D:THR980.O 42.62%
E:TYR266.N-E:THR51.O 42.62%
A:LYS287.N-A:LEU283.O 42.62%
D:GLN936.N-D:ASP932.O 42.62%
C:GLU184.N-C:GLY199.O 42.62%
C:VAL276.N-C:MET263.O 42.62%
A:TYR266.N-A:THR51.O 42.62%
F:SER861.N-F:ALA857.O 42.62%
F:GLN883.NE2-F:THR863.O 42.62%
E:GLU131.N-E:ASN155.O 42.62%
A:PHE47.N-E:PHE551.O 42.62%
C:MET263.N-C:VAL276.O 42.62%
A:SER289.OG-A:GLU285.O 42.62%
C:LYS287.N-C:LEU283.O 42.62%
E:CYS657.N-F:TYR677.O 42.62%
D:THR1048.N-D:SER703.O 42.62%
C:ARG495.NH2-C:ASP429.OD1 42.62%
E:ILE116.N-E:TRP101.O 42.62%
A:LYS142.N-A:SER239.O 42.62%
C:TYR195.N-C:LYS188.O 42.62%
F:GLN987.N-F:LEU983.O 42.62%
B:ARG747.N-B:THR743.O 42.62%
A:CYS657.N-B:TYR677.O 42.62%
Supplementary Information 405
D:THR863.OG1-D:LEU859.O 50.82%
C:VAL307.N-C:GLN614.O 50.82%
A:SER461.N-A:LYS465.O 50.82%
E:CYS133.N-E:ILE152.O 50.82%
F:SER798.OG-F:GLN1036.OE1 50.82%
D:SER798.OG-D:GLN1036.OE1 49.18%
B:TYR723.N-B:ASP719.O 49.18%
C:TYR266.N-C:THR51.O 49.18%
E:VAL562.N-E:LEU571.O 49.18%
B:LEU735.N-B:CYS731.O 49.18%
A:TYR88.N-A:GLY255.O 49.18%
A:VAL97.N-A:GLU93.OE1 49.18%
C:ALA127.N-C:PHE161.O 49.18%
D:LEU966.N-D:ILE962.O 49.18%
A:SER141.N-A:THR146.O 49.18%
C:SER141.N-C:THR146.O 49.18%
E:SER113.N-E:CYS128.O 49.18%
C:SER461.N-C:LYS465.O 49.18%
C:GLU131.N-C:ASN155.O 49.18%
E:THR425.OG1-E:ASP429.OD2 49.18%
B:MET770.N-F:ALA683.O 47.54%
C:VAL290.N-C:LEU286.O 62.30%
C:VAL114.N-C:PHE103.O 62.30%
B:GLN756.NE2-B:ILE752.O 60.66%
C:ASP572.N-C:THR539.O 60.66%
F:VAL1078.N-F:PHE1085.O 59.02%
F:GLN931.N-F:LEU927.O 59.02%
F:VAL945.N-F:LEU941.O 59.02%
E:VAL537.N-E:SER574.O 59.02%
E:VAL114.N-E:PHE103.O 59.02%
B:VAL1078.N-B:PHE1085.O 59.02%
B:SER701.N-B:VAL1050.O 57.38%
B:THR856.OG1-B:GLU801.OE2 57.38%
F:ALA1037.N-F:GLU801.OE2 57.38%
B:ALA1004.N-B:ILE1000.O 57.38%
F:ASN759.N-F:GLU755.O 57.38%
A:VAL642.N-B:ALA676.O 57.38%
A:ASP572.N-A:THR539.O 57.38%
B:ILE979.N-B:ILE975.O 57.38%
E:ILE115.N-E:ARG126.O 57.38%
C:VAL642.N-D:ALA676.O 57.38%
B:VAL945.N-B:LEU941.O 57.38%
A:PHE231.N-A:ILE81.O 47.54%
A:SER113.N-A:CYS128.O 47.54%
A:VAL66.N-A:HIS33.O 55.74%
A:GLU131.N-A:ASN155.O 55.74%
A:GLN546.N-A:GLN549.OE1 47.54%
E:VAL98.N-E:GLU93.OE1 47.54%
B:LEU966.N-B:ILE962.O 47.54%
E:TYR438.OH-E:ASP429.OD1 55.74%
B:ILE1000.N-B:ARG996.O 55.74%
A:VAL496.N-A:PHE387.O 55.74%
D:GLN1036.NE2-D:PRO1035.O 47.54%
B:THR922.OG1-B:GLU918.O 47.54%
E:ASP564.N-E:GLU569.O 55.74%
D:ILE979.N-D:ILE975.O 55.74%
C:ASP564.N-C:GLU569.O 47.54%
A:VAL98.N-A:GLU93.OE2 47.54%
C:PHE262.N-C:THR55.O 55.74%
C:VAL525.N-C:GLY536.O 55.74%
A:THR608.OG1-A:THR604.O 47.54%
F:SER1019.OG-F:GLU1013.OE1 50.82%
D:VAL675.N-C:SER659.O 62.30%
D:LEU735.N-D:CYS731.O 47.54%
C:LEU499.N-C:CYS419.O 50.82%
C:VAL496.N-C:PHE387.O 62.30%
F:THR863.OG1-F:LEU859.O 55.74%
E:VAL420.N-E:LYS365.O 50.82%
F:VAL711.N-F:HIS1040.O 62.30%
D:GLN987.N-D:LEU983.O 55.74%
E:VAL140.N-E:ALA237.O 50.82%
F:VAL1050.N-F:SER701.O 62.30%
B:ALA1037.N-B:GLU801.OE2 47.54%
E:PHE262.N-E:THR55.O 50.82%
C:TYR88.N-C:GLY255.O 62.30%
D:TYR677.OH-C:GLU647.O 47.54%
B:THR988.OG1-B:GLN984.O 50.82%
C:ASP267.N-C:THR271.O 62.30%
C:VAL66.N-C:HIS33.O 57.38%
C:CYS657.N-D:TYR677.O 50.82%
A:VAL290.N-A:LEU286.O 62.30%
F:GLN1036.NE2-F:PRO1035.O 57.38%
D:VAL1042.N-D:MET709.O 50.82%
D:VAL860.N-D:THR856.O 62.30%
Table 11.1 (continued)
C:SER289.OG-C:GLU285.O 47.54%
A:VAL596.N-A:ILE584.O 47.54%
E:SER141.N-E:THR146.O 47.54%
E:VAL97.N-E:GLU93.OE1 47.54%
C:VAL98.N-C:GLU93.OE1 47.54%
F:THR943.OG1-F:GLN939.O 47.54%
F:GLN1018.NE2-F:ARG887.O 47.54%
A:ASP429.N-A:THR425.O 47.54%
D:GLN993.N-D:TYR989.O 44.26%
F:SER1003.OG-F:GLU999.O 44.26%
D:VAL1047.N-D:MET1032.O 44.26%
F:VAL1047.N-F:MET1032.O 44.26%
C:PHE89.N-C:PHE185.O 44.26%
F:ILE1086.N-F:GLN1095.O 44.26%
C:ASP154.N-C:GLU131.O 44.26%
F:LEU966.N-F:ILE962.O 44.26%
C:LEU216.N-C:VAL40.O 44.26%
A:ILE573.N-A:ASP560.O 44.26%
F:THR921.OG1-F:GLN917.O 44.26%
D:SER703.N-D:THR1048.O 44.26%
F:SER1052.N-F:ASN699.O 44.26%
E:ARG495.NH2-E:ASP429.OD1 44.26%
E:ASP385.N-E:VAL498.O 44.26%
E:LEU499.N-E:CYS419.O 44.26%
C:THR229.N-C:GLY104.O 44.26%
C:PHE231.N-C:ILE81.O 44.26%
E:ASP560.N-E:GLY552.O 40.98%
E:PHE231.N-E:ILE81.O 40.98%
E:ILE203.N-E:LYS180.O 40.98%
E:VAL606.N-E:ASN602.O 40.98%
C:ILE584.N-C:VAL596.O 40.98%
D:ALA997.N-D:GLN993.O 40.98%
B:ILE913.N-B:PHE909.O 40.98%
A:ILE428.N-A:THR425.O 40.98%
E:ALA91.N-E:ARG183.O 40.98%
C:ARG495.NE-C:ASP429.OD2 40.98%
C:VAL97.N-C:GLU93.OE1 40.98%
A:ILE584.N-A:VAL596.O 40.98%
B:SER750.N-B:ASN746.O 40.98%
B:SER717.N-B:THR841.O 40.98%
B:ALA906.N-B:GLN902.O 40.98%
B:THR1059.OG1-B:PHE1077.O 40.98%
C:THR425.OG1-C:ASP429.OD2 40.98%
A:LEU499.N-A:CYS419.O 40.98%
A:VAL420.N-A:LYS365.O 40.98%
E:LEU194.N-E:LEU222.O 40.98%
C:PHE187.N-C:ILE87.O 40.98%
406 11 SARS (SARS-CoV-1)
E:CYS278.N-E:THR261.O 31.15% E:SER279.OG-E:ASP277.OD1 31.15% A:ASP560.N-A:GLY552.O 31.15% D:THR980.N-D:ASP976.O 31.15%
A:ILE219.N-A:VAL196.O 34.43% A:LEU194.N-A:LEU222.O 34.43% A:ILE125.N-A:TYR163.O 34.43% A:ASN409.ND2-A:ILE405.O 34.43%
B:THR943.N-B:GLN939.O 37.70%
D:THR943.OG1-D:GLN939.O 37.70%
A:LEU216.N-A:VAL40.O 37.70%
C:VAL98.N-C:GLU93.OE2 37.70%
E:THR425.N-E:PRO493.O 37.70%
B:ILE694.N-B:PHE1057.O 37.70%
D:ILE694.N-D:PHE1057.O 37.70%
C:ILE115.N-C:ARG126.O 39.34%
C:GLN492.NE2-C:THR487.O 39.34%
D:ALA906.N-D:GLN902.O 39.34%
D:MET884.N-D:PHE880.O 39.34%
F:PHE909.N-F:ILE905.O 39.34%
F:SER703.N-F:THR1048.O 39.34%
D:SER1012.N-D:ALA1008.O 37.70%
E:ASN119.N-E:ASN122.O 37.70%
D:GLN883.NE2-D:THR863.O 37.70%
C:VAL606.N-C:ASN602.O 37.70%
E:TYR41.OH-E:LEU58.O 39.34%
E:ILE81.N-E:PHE231.O 39.34%
A:GLY104.N-A:ASN230.O 39.34%
A:THR425.N-A:PRO493.O 37.70%
C:THR92.N-C:ALA251.O 39.34%
A:PHE187.N-A:ILE87.O 39.34%
E:LEU636.N-E:PHE629.O 37.70%
B:ALA695.N-D:GLN877.O 37.70%
E:SER289.OG-E:GLU285.O 39.34%
E:SER461.N-E:LYS465.O 37.70%
E:ALA384.N-E:LYS343.O 37.70%
C:VAL596.N-C:ILE584.O 39.34%
F:THR988.OG1-F:GLN984.O 39.34%
C:SER370.N-F:ARG965.O 37.70%
B:ALA1008.N-B:ALA1004.O 39.34%
B:THR991.OG1-B:GLN987.O 39.34%
E:TRP101.N-E:ILE116.O 37.70%
B:GLN1036.NE2-B:PRO1035.O 37.70%
D:THR922.N-D:GLU918.O 37.70%
C:THR71.N-C:ALA250.O 39.34%
A:MET151.N-A:PHE137.O 39.34%
F:VAL767.N-F:PHE764.O 39.34%
A:ILE621.N-A:GLN280.O 34.43%
D:PHE1057.N-D:ILE694.O 37.70%
E:PHE253.N-E:ALA90.O 39.34%
E:VAL596.N-E:ILE584.O 37.70%
B:ILE696.N-B:ARG1055.O 37.70%
A:LEU182.N-A:GLN201.O 39.34%
E:GLU184.N-E:GLY199.O 37.70%
C:VAL140.N-C:ALA237.O 37.70%
E:GLY552.N-E:SER561.O 39.34%
A:ALA384.N-A:LYS343.O 39.34%
B:PHE1057.N-B:ILE694.O 31.15%
F:GLN992.N-F:THR988.O 34.43% E:ILE621.N-E:GLN280.O 34.43%
A:SER370.N-D:ARG965.O 37.70%
F:GLN993.N-F:TYR989.O 39.34%
D:ILE696.N-D:ARG1055.O 39.34%
C:ASN435.ND2-C:ASP429.O 31.15%
D:SER750.N-D:ASN746.O 34.43%
E:LEU571.N-E:VAL562.O 37.70%
F:THR922.OG1-F:GLU918.O 39.34%
B:ILE905.N-B:ASN901.O 34.43%
C:TYR383.N-C:SER500.O 34.43%
A:ASN118.N-A:ARG99.O 34.43%
E:THR148.N-E:ALA139.O 34.43%
C:ASN189.N-C:ASP85.O 34.43%
A:VAL186.N-A:TYR197.O 34.43%
B:SER964.OG-B:ASN960.O 34.43%
C:LYS258.N-C:PHE59.O 34.43%
A:VAL562.N-A:LEU571.O 34.43%
C:LEU571.N-C:VAL562.O 34.43%
C:VAL562.N-C:LEU571.O 34.43%
A:LEU264.N-A:TYR53.O 34.43%
F:ALA1007.N-F:SER1003.O 34.43%
D:ILE916.N-D:ALA912.O 34.43%
D:GLN1018.NE2-D:HIS1030.O 34.43%
B:VAL1076.N-B:THR1087.O 34.43%
F:PHE1085.N-F:VAL1078.O 34.43%
(continued)
B:VAL897.N-B:THR894.O 31.15%
A:ARG441.N-A:ASN409.OD1 31.15%
E:TYR383.N-E:SER500.O 31.15%
E:ASN189.N-E:ASP85.O 31.15%
C:PHE253.N-C:ALA90.O 31.15%
B:THR980.OG1-B:ASP976.O 31.15%
D:THR988.N-D:GLN984.O 31.15%
F:THR988.N-F:GLN984.O 31.15%
A:VAL606.N-A:ASN602.O 31.15%
A:SER607.OG-A:CYS603.O 31.15%
F:TYR677.N-E:CYS657.O 31.15%
D:LEU1045.N-D:PHE1034.O 31.15%
D:SER1052.N-D:ASN699.O 31.15%
B:PHE888.N-B:MET884.O 31.15%
A:VAL389.N-A:TYR494.O 31.15%
C:PHE460.N-C:TYR475.O 31.15%
A:TYR367.N-A:GLY418.O 31.15%
E:TYR195.N-E:LYS188.O 31.15%
E:LEU222.N-E:LEU194.O 31.15%
E:GLY255.N-E:TYR88.O 31.15%
A:LYS265.N-A:ASP274.O 37.70%
F:LYS1010.N-F:LEU1006.O 39.34%
C:ASN479.N-C:TYR440.O 34.43%
D:LYS1010.N-D:LEU1006.O 37.70%
B:THR943.OG1-B:GLN939.O 37.70%
F:ILE913.N-F:PHE909.O 39.34%
B:LEU840.N-B:ASN838.OD1 31.15%
A:SER582.N-A:TYR598.O 31.15%
B:GLN992.N-B:THR988.O 31.15%
F:GLN939.N-F:ASN935.O 31.15%
B:LEU843.N-B:LYS715.O 31.15%
D:THR1048.OG1-D:LYS1027.O 39.34%
E:VAL98.N-E:GLU93.OE2 34.43%
E:LYS258.N-E:PHE59.O 34.43%
A:GLY68.N-A:THR31.O 34.43%
F:ILE724.N-F:CYS720.O 34.43%
C:SER607.OG-C:CYS603.O 34.43%
F:ALA754.N-F:SER750.O 31.15%
A:VAL583.N-A:TYR300.O 37.70%
A:TYR383.N-A:SER500.O 39.34%
D:ALA1037.N-D:GLU801.OE2 31.15%
D:ILE975.N-D:ALA971.O 39.34%
F:SER717.N-F:THR841.O 34.43% B:THR988.N-B:GLN984.O 34.43%
F:ARG761.N-F:ASP757.O 37.70%
B:GLN993.N-B:TYR989.O 37.70%
B:THR921.OG1-B:GLN917.O 31.15%
D:GLY862.N-D:ALA858.O 31.15%
F:VAL897.N-F:THR894.O 31.15%
F:THR1059.OG1-F:PHE1077.O 31.15%
F:THR1059.OG1-F:PHE1077.O 31.15%
E:LEU182.N-E:GLN201.O 39.34%
E:VAL583.N-E:TYR300.O 34.43%
B:ARG761.N-B:ASP757.O 34.43%
D:SER919.OG-D:GLN915.O 34.43%
F:GLY867.N-F:GLY862.O 34.43%
F:GLY867.N-F:GLY862.O 34.43%
E:PHE187.N-E:ILE87.O 39.34%
D:GLU900.N-D:ASN896.O 37.70%
D:HIS1046.N-D:THR705.O 37.70%
B:PHE1085.N-B:VAL1078.O 37.70%
E:MET263.N-E:VAL276.O 39.34%
E:VAL276.N-E:MET263.O 39.34%
B:TYR1070.N-B:ILE1063.O 37.70%
D:LEU983.N-D:ILE979.O 39.34%
B:TYR1070.N-B:ILE1063.O 37.70%
E:LYS265.N-E:ASP274.O 39.34%
E:LYS265.N-E:ASP274.O 39.34%
Table 11.2 The HBs of MD 5x58 SARS-CoV-1 spike trimer with occupancy rates ≥30% during the 741 μs’ MD (continuation)
Supplementary Information 407
E:ASN435.N-E:PHE483.O 34.43% D:ILE724.N-D:CYS720.O 34.43% A:PHE83.N-A:THR229.O 34.43% C:LEU222.N-C:LEU194.O 34.43% E:ARG441.N-E:ASN409.OD1 34.43% D:SER861.N-D:ALA857.O 34.43% F:GLN984.N-F:THR980.O 34.43% D:THR943.N-D:GLN939.O 34.43% A:TYR163.N-A:ILE125.O 34.43% E:ARG495.NE-E:ASP429.OD2 34.43% B:GLN987.N-B:LEU983.O 34.43% D:TYR1070.N-D:ILE1063.O 32.79% B:GLN1018.NE2-B:HIS1030.O 32.79% F:TYR1049.N-F:TYR1029.O 32.79% D:ASN759.N-D:GLU755.O 32.79% D:THR980.OG1-D:ASP976.O 32.79% E:PHE83.N-E:THR229.O 32.79% D:ALA885.N-D:ALA881.O 32.79% D:TYR1049.N-D:TYR1029.O 32.79% B:SER1019.OG-B:GLU1013.OE1 32.79%
D:THR1059.OG1-D:PHE1077.O 36.07%
F:ILE905.N-F:ASN901.O 36.07%
F:MET884.N-F:PHE880.O 36.07%
F:ALA912.N-F:GLN908.O 36.07%
F:ALA1008.N-F:ALA1004.O 36.07%
B:ASN759.N-B:GLU755.O 36.07%
F:ALA676.N-E:GLU640.O 36.07%
F:VAL934.N-F:LEU930.O 36.07%
D:TYR723.N-D:ASP719.O 36.07%
A:MET263.N-A:VAL276.O 36.07%
E:GLU93.N-E:HIS181.O 36.07%
E:LYS198.N-E:LYS217.O 36.07%
B:THR705.N-B:HIS1046.O 36.07%
F:THR1048.N-F:SER703.O 36.07%
B:HIS1046.N-B:THR705.O 36.07%
B:SER798.OG-B:GLN1036.OE1 36.07%
B:VAL934.N-B:LEU930.O 36.07%
C:ILE652.N-C:ILE656.O 36.07%
A:ILE117.N-A:VAL124.O 36.07%
A:ASP154.N-A:GLU131.O 36.07%
D:VAL897.N-D:THR894.O 36.07%
F:ALA906.N-F:GLN902.O 36.07%
E:LYS142.N-E:SER239.O 39.34%
C:TYR41.OH-C:LEU58.O 39.34%
C:GLN546.N-C:GLN549.OE1 34.43%
F:LEU983.N-F:ILE979.O 34.43%
B:ALA676.N-A:GLU640.O 34.43%
B:ILE1086.N-B:GLN1095.O 36.07%
C:ASN230.N-C:GLY104.O 39.34%
F:SER701.N-F:VAL1050.O 34.43%
F:THR980.OG1-F:ASP976.O 37.70%
D:VAL808.N-D:LEU804.O 39.34%
A:THR229.N-A:GLY104.O 39.34%
Table 11.2 (continued)
C:TYR197.N-C:VAL186.O 31.15%
B:GLN931.N-B:LEU927.O 31.15%
C:SER353.OG-C:ASP351.OD1 31.15%
E:ALA127.N-E:PHE161.O 31.15%
A:CYS128.N-A:SER113.O 31.15%
B:THR841.N-B:SER717.O 31.15%
E:ILE584.N-E:VAL596.O 31.15%
D:PHE1044.N-D:GLU707.O 31.15%
A:THR487.OG1-A:TYR484.O 31.15%
D:PHE888.N-D:MET884.O 31.15%
D:SER964.OG-D:ASN960.O 31.15%
E:THR92.N-E:ALA251.O 31.15%
C:ILE203.N-C:LYS180.O 31.15%
F:ASP719.N-F:GLY839.O 31.15%
B:ASN942.N-B:ALA938.O 31.15%
B:LEU1045.N-B:PHE1034.O 31.15%
A:ARG495.NH2-A:ASP429.OD1 31.15%
C:CYS128.N-C:SER113.O 31.15%
D:ASP967.N-A:SER370.OG 31.15%
A:ASN189.N-A:ASP85.O 31.15%
A:VAL314.N-A:ASN528.O 31.15%
A:SER64.OG-A:PRO61.O 31.15%
D:THR760.OG1-D:GLN756.O 31.15%
D:ILE905.N-D:ASN901.O 31.15%
408 11 SARS (SARS-CoV-1)
F:THR991.N-F:GLN987.O 31.15%
C:ALA284.N-C:ASN281.OD1 32.79% C:VAL102.N-C:ARG232.O 32.79% E:ASP154.N-E:GLU131.O 32.79% E:ILE428.N-E:THR425.O 32.79% C:ILE428.N-C:THR425.O 32.79% B:LYS1010.N-B:LEU1006.O 32.79% F:LEU843.N-F:LYS715.O 32.79% D:THR991.N-D:GLN987.O 32.79% E:LEU264.N-E:TYR53.O 32.79% E:PHE103.N-E:VAL114.O 32.79% C:VAL382.N-C:ILE345.O 32.79% F:HIS1046.N-F:THR705.O 32.79% E:THR608.OG1-E:THR604.O 32.79%
A:THR567.OG1-A:ASP564.OD1 36.07%
E:SER370.N-B:ARG965.O 36.07%
E:CYS128.N-E:SER113.O 36.07%
C:CYS133.N-C:ILE152.O 36.07%
E:SER35.N-E:SER64.O 36.07%
A:GLN549.N-A:GLN546.O 36.07%
A:TYR440.N-A:ASN479.O 36.07%
D:LEU843.N-D:LYS715.O 36.07%
A:TRP101.N-A:ILE116.O 36.07%
A:PHE103.N-A:VAL114.O 36.07%
B:ALA1007.N-B:SER1003.O 36.07%
C:ASN435.N-C:PHE483.O 36.07%
B:SER861.OG-B:ALA857.O 36.07%
B:ASP719.N-B:GLY839.O 32.79%
F:THR841.N-F:SER717.O 32.79%
A:ARG342.NE-A:ASP385.OD1 32.79%
A:VAL98.N-A:GLU93.OE1 32.79%
C:GLY552.N-C:SER561.O 32.79%
F:ILE752.N-F:ALA748.O 32.79%
C:HIS181.N-C:GLU93.O 32.79%
A:ILE81.N-A:PHE231.O 32.79%
C:SER292.N-C:LYS287.O 32.79%
C:VAL581.N-C:THR302.O 32.79%
F:ASN1080.N-F:SER1083.O 32.79%
A:ASN119.N-A:ASN122.O 32.79%
F:LEU735.N-F:CYS731.O 32.79%
A:VAL394.N-A:LYS390.O 31.15%
B:TYR677.N-A:CYS657.O 32.79%
A:ALA284.N-A:ASN281.OD1 36.07%
Supplementary Information 409
B:VAL593.N-B:LEU581.O 63.93%
B:PHE326.N-B:ILE315.O 63.93%
A:VAL314.N-A:ASN403.O 63.93%
B:VAL609.N-B:PHE522.O 63.93%
C:TYR437.OH-C:LEU255.O 63.93%
A:ASN285.ND2-A:ILE39.O 63.93%
A:THR41.OG1-A:ILE217.O 63.93%
B:ILE640.N-B:THR676.O 63.93%
A:VAL675.N-A:LEU662.O 63.93%
C:VAL675.N-C:LEU662.O 63.93%
B:SER26.N-B:GLN29.OE1 63.93%
C:THR930.N-C:MET926.O 63.93%
C:SER932.OG-C:MET928.O 63.93%
C:VAL1149.N-C:TYR1153.O 63.93%
B:VAL517.N-B:ILE566.O 63.93%
B:VAL1059.N-B:ALA1055.O 63.93%
C:VAL1007.N-C:ALA1003.O 63.93%
A:ILE632.N-A:TYR635.O 62.30%
B:VAL194.N-B:THR38.O 62.30%
A:VAL427.N-A:GLY247.O 62.30%
C:LEU1127.N-C:ASN1120.O 62.30%
B:SER932.OG-B:MET928.O 62.30%
B:ILE983.N-B:PHE979.O 62.30%
A:ILE983.N-A:PHE979.O 62.30%
C:VAL362.N-C:SER355.O 62.30%
C:THR584.OG1-C:SER589.O 62.30%
A:VAL32.N-A:MET27.O 62.30%
B:ALA1055.N-B:ASP1051.O 60.66%
B:TYR437.OH-B:LEU255.O 60.66%
B:VAL686.N-B:GLY457.O 60.66%
B:GLN1015.N-B:LEU1011.O 60.66%
A:VAL1059.N-A:ALA1055.O 60.66%
B:VAL1132.N-B:SER772.O 85.25%
A:VAL1132.N-A:SER772.O 85.25%
C:VAL425.N-C:SER249.O 81.97%
B:VAL425.N-B:SER249.O 80.33%
C:VAL378.N-C:MET296.O 78.69%
B:VAL162.N-B:GLU147.O 78.69%
A:VAL162.N-A:GLU147.O 78.69%
A:VAL1084.N-A:LYS1080.O 78.69%
C:VAL1132.N-C:SER772.O 78.69%
A:VAL598.N-A:CYS577.O 77.05%
B:VAL378.N-B:MET296.O 77.05%
B:VAL192.N-B:VAL40.O 77.05%
A:VAL1074.N-A:LEU1070.O 77.05%
C:VAL786.N-C:MET915.O 77.05%
C:VAL829.N-C:GLU825.O 77.05%
B:VAL1185.N-B:ASP1188.OD2 77.05%
A:VAL366.N-A:CYS351.O 75.41%
A:VAL316.N-A:ASN401.O 75.41%
C:VAL987.N-C:ILE983.O 75.41%
A:VAL1185.N-A:ASP1188.OD2 75.41%
A:VAL1141.N-A:LEU763.O 75.41%
B:VAL1074.N-B:LEU1070.O 73.77%
A:VAL686.N-A:GLY457.O 73.77%
A:VAL829.N-A:GLU825.O 73.77%
C:GLU1097.N-C:GLN1093.O 73.77%
C:VAL1141.N-C:LEU763.O 73.77%
A:VAL378.N-A:MET296.O 73.77%
B:VAL149.N-B:PHE160.O 73.77%
C:THR41.OG1-C:ILE217.O 72.13%
B:VAL1141.N-B:LEU763.O 72.13%
C:VAL1173.N-C:ARG1182.O 72.13%
B:VAL1173.N-B:ARG1182.O 72.13%
C:PHE326.N-C:ILE315.O 57.38%
A:ASP1150.N-A:ILE1202.O 57.38%
B:VAL1190.N-B:VAL1156.O 57.38%
B:VAL32.N-B:MET27.O 57.38%
B:VAL598.N-B:CYS577.O 57.38%
A:VAL1149.N-A:TYR1153.O 57.38%
A:SER978.OG-A:ILE974.O 57.38%
C:HIS1130.N-C:GLN774.O 57.38%
C:GLN1015.N-C:LEU1011.O 57.38%
C:LEU77.N-C:ILE89.O 57.38%
C:VAL173.N-C:SER56.O 57.38%
B:VAL717.N-B:ALA694.O 57.38%
B:LEU151.N-B:ARG158.O 57.38%
B:ILE674.N-B:ARG642.O 57.38%
C:VAL194.N-C:THR38.O 57.38%
C:MET296.N-C:VAL378.O 57.38%
A:PHE326.N-A:ILE315.O 57.38%
C:VAL598.N-C:CYS577.O 59.02%
C:VAL609.N-C:PHE522.O 59.02%
C:ILE983.N-C:PHE979.O 59.02%
A:ARG1088.NH1-A:ILE780.O 59.02%
C:VAL717.N-C:ALA694.O 59.02%
B:VAL293.N-B:PHE275.O 59.02%
A:TYR1155.N-A:ILE1147.O 59.02%
B:ALA1091.N-B:SER1087.O 59.02%
A:VAL173.N-A:SER56.O 59.02%
B:VAL786.N-B:MET915.O 59.02%
A:LYS444.N-A:SER440.O 59.02%
A:THR196.OG1-A:PRO33.O 59.02%
B:MET296.N-B:VAL378.O 59.02%
A:VAL609.N-A:PHE522.O 59.02%
C:VAL316.N-C:ASN401.O 59.02%
Table 11.3 The HBs of MD of HCoV-NL63 spike trimer with occupancy rates ≥30% during the 651 μs’ MD B:VAL202.N-B:THR195.O 54.10%
A:VAL91.N-A:PHE75.O 52.46%
C:LYS107.N-C:ASP125.O 52.46%
C:LEU151.N-C:ARG158.O 52.46%
C:VAL32.N-C:MET27.O 52.46%
B:VAL421.N-B:GLN253.O 52.46%
A:ILE376.N-A:TYR298.O 52.46%
A:PHE352.N-A:TYR327.O 52.46%
A:LEU1134.N-A:THR770.O 52.46%
B:VAL101.N-B:PHE132.O 52.46%
B:VAL91.N-B:PHE75.O 52.46%
C:CYS737.N-C:SER741.O 52.46%
A:VAL717.N-A:ALA694.O 52.46%
B:VAL186.N-B:GLY62.O 52.46%
A:ASN625.N-A:ILE641.O 52.46%
C:VAL423.N-C:LEU251.O 52.46%
C:ASN285.ND2-C:ILE39.O 52.46%
B:LEU238.N-B:GLN253.OE1 52.46%
B:LYS564.N-B:SER601.O 52.46%
B:LEU581.N-B:GLY594.O 52.46%
C:ALA1091.N-C:SER1087.O 54.10%
B:SER249.N-B:VAL425.O 54.10%
C:VAL1018.N-C:ILE1014.O 54.10%
A:VAL793.N-A:CYS789.O 54.10%
B:TYR792.OH-B:ARG1066.O 54.10%
A:GLN433.N-A:ASN426.O 54.10%
C:THR1209.OG1-C:GLU1206.O 54.10%
B:VAL745.N-B:ASN733.O 54.10%
A:THR102.N-A:THR92.O 54.10%
B:VAL173.N-B:SER56.O 54.10%
C:LEU171.N-C:TYR58.O 54.10%
A:LEU151.N-A:ARG158.O 54.10%
410 11 SARS (SARS-CoV-1)
C:VAL91.N-C:PHE75.O 52.46%
A:VAL415.N-A:TRP261.O 52.46%
B:GLY735.N-B:ILE743.O 50.82% A:PHE1128.N-A:GLU776.O 50.82%
C:TYR298.N-C:ILE376.O 54.10% C:VAL377.N-C:TYR385.O 54.10% C:ASN285.N-C:LEU260.O 54.10% C:VAL474.N-C:ASN631.O 54.10% A:VAL194.N-A:THR38.O 54.10% B:PHE673.N-B:PHE664.O 54.10%
C:ALA583.N-C:THR591.O 65.57%
C:ILE632.N-C:TYR635.O 65.57%
A:ILE674.N-A:ARG642.O 65.57%
B:VAL829.N-B:GLU825.O 65.57%
A:VAL192.N-A:VAL40.O 65.57%
A:ILE736.N-A:MET729.O 50.82%
C:ARG1182.NH2-C:ASP1188.OD1 50.82%
C:LEU257.N-C:GLY224.O 50.82%
B:VAL362.N-B:SER355.O 50.82%
C:SER767.N-C:ASP1137.O 50.82%
A:MET928.N-A:GLU924.O 50.82%
B:THR196.N-B:SER36.O 50.82% C:VAL793.N-C:CYS789.O 50.82%
B:VAL314.N-B:ASN403.O 54.10%
C:ILE640.N-C:THR676.O 65.57%
B:ARG1088.NH1-B:ILE780.O 65.57%
C:VAL192.N-C:VAL40.O 65.57%
C:VAL1084.N-C:LYS1080.O 50.82% A:ILE357.N-A:THR360.O 50.82%
B:THR584.OG1-B:SER589.O 54.10%
B:ILE376.N-B:TYR298.O 50.82% C:TRP261.N-C:VAL415.O 50.82% C:SER172.N-C:ALA76.O 50.82%
B:HIS1130.N-B:GLN774.O 55.74% C:VAL517.N-C:ILE566.O 55.74%
A:VAL1173.N-A:ARG1182.O 67.21%
B:THR1209.OG1-B:GLU1206.O 67.21%
B:ILE1211.N-B:LEU1207.O 50.82% A:VAL377.N-A:TYR385.O 50.82%
A:VAL728.N-A:ILE736.O 55.74% C:THR1008.OG1-C:ILE1004.O 55.74%
C:ARG1088.NH1-C:ILE780.O 67.21%
B:VAL987.N-B:ILE983.O 67.21%
C:VAL427.N-C:GLY247.O 65.57%
C:ASN959.N-C:GLN955.O 50.82% C:VAL1163.N-C:THR1174.O 50.82%
A:VAL517.N-A:ILE566.O 55.74% B:MET695.N-B:GLN683.O 55.74%
A:VAL149.N-A:PHE160.O 67.21%
C:ILE674.N-C:ARG642.O 50.82% A:GLN774.N-A:HIS1130.O 50.82%
A:SER932.OG-A:MET928.O 55.74% B:GLU1097.N-B:GLN1093.O 55.74%
A:TYR437.OH-A:LEU255.O 67.21%
B:ILE632.N-B:TYR635.O 67.21%
A:VAL786.N-A:MET915.O 67.21%
C:VAL421.N-C:GLN253.O 50.82% B:LEU804.N-B:CYS800.O 50.82%
C:VAL728.N-C:ILE736.O 55.74% B:THR930.N-B:MET926.O 55.74%
C:VAL1074.N-C:LEU1070.O 68.85%
C:VAL366.N-C:CYS351.O 67.21%
B:TYR298.N-B:ILE376.O 50.82% A:ASN285.N-A:LEU260.O 50.82%
A:TYR716.OH-A:GLY740.O 55.74% C:THR102.N-C:THR92.O 55.74%
A:VAL362.N-A:SER355.O 68.85%
A:ASN387.N-A:GLU375.O 68.85%
B:ILE340.N-B:LYS311.O 52.46% B:ALA583.N-B:THR591.O 50.82%
C:ASN625.N-C:ILE641.O 55.74% B:ASN625.N-B:ILE641.O 55.74% B:THR196.OG1-B:PRO33.O 55.74%
C:VAL162.N-C:GLU147.O 68.85%
A:VAL1190.N-A:VAL1156.O 68.85%
B:VAL675.N-B:LEU662.O 68.85%
B:THR92.OG1-B:SER73.O 52.46% A:LEU1133.N-A:THR1113.O 52.46%
A:MET296.N-A:VAL378.O 55.74% C:THR196.OG1-C:PRO33.O 55.74%
B:VAL316.N-B:ASN401.O 68.85%
C:VAL1059.N-C:ALA1055.O 68.85%
A:VAL1018.N-A:ILE1014.O 52.46%
C:VAL593.N-C:LEU581.O 55.74% B:PHE352.N-B:TYR327.O 55.74%
B:VAL1149.N-B:TYR1153.O 60.66%
B:VAL728.N-B:ILE736.O 60.66%
A:VAL421.N-A:GLN253.O 70.49%
B:VAL366.N-B:CYS351.O 68.85%
A:LYS564.N-A:SER601.O 52.46% C:VAL882.N-C:PHE878.O 52.46%
A:HIS78.N-A:LYS170.O 57.38% B:ILE1192.N-B:GLY1154.O 57.38%
B:VAL1018.N-B:ILE1014.O 60.66%
A:GLU1097.N-A:GLN1093.O 60.66%
A:VAL182.N-A:ILE66.O 70.49%
C:VAL1185.N-C:ASP1188.OD2 70.49%
B:SER978.OG-B:ILE974.O 52.46% C:VAL1190.N-C:VAL1156.O 52.46%
C:VAL149.N-C:PHE160.O 57.38% B:ARG150.N-B:THR143.O 57.38%
B:VAL1084.N-B:LYS1080.O 60.66%
A:VAL1163.N-A:THR1174.O 60.66%
A:VAL425.N-A:SER249.O 70.49%
A:VAL987.N-A:ILE983.O 70.49%
A:ALA1091.N-A:SER1087.O 52.46% C:SER978.OG-C:ILE974.O 52.46%
A:TYR298.N-A:ILE376.O 57.38% A:LEU238.N-A:GLN253.OE1 57.38%
B:ASN285.ND2-B:ILE39.O 60.66%
C:VAL686.N-C:GLY457.O 60.66%
C:VAL182.N-C:ILE66.O 72.13%
B:VAL182.N-B:ILE66.O 72.13%
Supplementary Information 411
A:LEU257.N-A:GLY224.O 45.90%
C:SER36.OG-C:ASP34.O 45.90%
C:MET695.N-C:GLN683.O 45.90%
A:SER184.OG-A:HIS47.O 45.90%
B:SER184.OG-B:HIS47.O 45.90%
C:TYR687.N-C:SER690.O 45.90%
A:GLN706.N-A:SER718.O 45.90%
B:TYR687.N-B:SER690.O 45.90%
C:TYR716.OH-C:GLY740.O 45.90%
A:LEU77.N-A:ILE89.O 45.90%
A:ILE780.N-A:ASP1124.O 45.90%
A:HIS1130.N-A:GLN774.O 45.90%
C:LYS564.N-C:SER601.O 45.90%
B:THR791.OG1-B:ASP788.OD1 45.90%
B:LYS444.N-B:SER440.O 45.90%
B:LYS104.N-B:TYR90.O 45.90%
A:ILE1192.N-A:GLY1154.O 45.90%
C:VAL202.N-C:THR195.O 45.90%
A:PHE673.N-A:PHE664.O 45.90%
C:SER145.N-C:THR148.O 45.90%
C:VAL856.N-C:LEU853.O 45.90%
B:CYS567.N-B:THR599.O 45.90%
A:TYR391.N-A:PHE384.O 45.90%
C:GLU815.N-C:CYS811.O 45.90%
C:PHE487.N-C:ARG525.O 44.26%
C:LEU581.N-C:GLY594.O 44.26%
B:PHE579.N-B:LEU596.O 44.26%
C:ALA416.N-C:ARG297.O 44.26%
A:TRP261.N-A:VAL415.O 44.26%
A:THR1029.OG1-A:LEU1025.O 44.26%
A:ARG150.N-A:THR143.O 44.26%
B:VAL684.N-B:TYR459.O 44.26%
A:LEU171.N-A:TYR58.O 44.26%
A:TYR90.N-A:LYS104.O 44.26%
A:GLN1015.N-A:LEU1011.O 44.26%
C:PHE1128.N-C:GLU776.O 44.26%
C:PHE563.N-C:ILE606.O 49.18%
A:VAL474.N-A:ASN631.O 49.18%
C:GLN433.N-C:ASN426.O 49.18%
A:ASN193.N-A:THR205.O 49.18%
B:VAL40.N-B:VAL192.O 49.18%
A:SER26.N-A:GLN29.OE1 49.18%
A:SER172.N-A:ALA76.O 49.18%
A:VAL882.N-A:PHE878.O 49.18%
C:MET926.N-C:ASP922.O 49.18%
B:LEU1127.N-B:ASN1120.O 49.18%
A:GLN1092.N-A:ARG1088.O 49.18%
A:LEU1127.N-A:ASN1120.O 49.18%
A:THR1131.N-A:PHE1116.O 49.18%
C:LYS1139.N-C:ILE765.O 49.18%
B:TYR1155.N-B:ILE1147.O 49.18%
C:VAL400.N-C:VAL273.O 49.18%
B:VAL474.N-B:ASN631.O 49.18%
C:ASN193.N-C:THR205.O 49.18%
C:SER249.N-C:VAL425.O 49.18%
A:ALA685.N-A:GLY693.O 49.18%
C:THR483.OG1-C:THR519.OG1 49.18%
A:VAL40.N-A:VAL192.O 49.18%
A:MET695.N-A:GLN683.O 49.18%
A:VAL593.N-A:LEU581.O 49.18%
A:ASN354.N-A:LEU325.O 47.54%
A:LEU581.N-A:GLY594.O 47.54%
C:CYS567.N-C:THR599.O 47.54%
B:ASN387.N-B:GLU375.O 47.54%
B:THR419.N-B:ARG256.O 47.54%
B:THR41.OG1-B:ILE217.O 47.54%
A:VAL202.N-A:THR195.O 47.54%
C:SER184.OG-C:HIS47.O 47.54%
A:TYR65.N-A:LEU140.O 47.54%
C:LEU820.N-C:ASP816.O 47.54%
B:PHE1128.N-B:GLU776.O 47.54%
C:ILE1211.N-C:LEU1207.O 47.54%
A:LEU300.N-A:ARG374.O 40.98%
B:ARG380.N-B:ASP294.O 40.98%
A:ILE1211.N-A:LEU1207.O 40.98%
C:CYS1148.N-C:VAL1200.O 40.98%
A:CYS1148.N-A:VAL1200.O 40.98%
B:VAL1163.N-B:THR1174.O 40.98%
B:ARG1176.N-B:ASN1161.O 40.98%
A:SER841.OG-A:SER837.O 40.98%
A:LYS1100.N-A:ILE1095.O 40.98%
C:MET928.N-C:GLU924.O 40.98%
A:ILE743.N-A:GLY735.O 40.98%
A:TYR687.N-A:SER690.O 40.98%
C:TYR65.N-C:LEU140.O 40.98%
A:ALA908.N-A:ASP904.O 40.98%
C:ARG150.N-C:THR143.O 40.98%
A:SER428.N-A:ASN431.O 40.98%
B:VAL273.N-B:VAL400.O 40.98%
A:ILE524.N-A:ASN558.OD1 40.98%
B:LYS318.N-B:ALA399.O 40.98%
A:THR584.OG1-A:SER589.O 40.98%
B:TYR90.N-B:LYS104.O 42.62%
A:SER249.N-A:VAL425.O 42.62%
C:ASN354.N-C:LEU325.O 42.62%
B:ARG1105.NH1-B:GLU1097.OE1 42.62%
A:CYS351.N-A:GLY367.O 42.62%
C:ALA988.N-C:ASN984.O 42.62%
C:GLN1092.N-C:ARG1088.O 42.62%
C:HIS78.N-C:LYS170.O 42.62%
A:ILE640.N-A:THR676.O 42.62%
B:GLN1092.N-B:ARG1088.O 42.62%
A:LEU103.N-A:LEU130.O 42.62%
A:PHE49.N-A:PHE183.O 42.62%
A:THR791.OG1-A:ASP788.OD2 42.62%
C:CYS800.N-C:ASN797.OD1 42.62%
B:ASN285.N-B:LEU260.O 42.62%
B:TRP261.N-B:VAL415.O 42.62%
Table 11.4 The HBs of MD of HCoV-NL63 spike trimer with occupancy rates ≥30% during the 651 μs’ MD (continuation 1)
A:ILE606.N-A:PHE563.O 39.34%
B:SER772.N-B:VAL1132.O 39.34%
C:PHE840.N-C:ASP836.O 39.34%
A:ASN1096.N-A:GLN1092.O 39.34%
C:THR92.OG1-C:SER73.O 39.34%
A:PHE64.N-A:SER184.O 39.34%
B:GLU815.N-B:CYS811.O 39.34%
C:SER26.OG-C:TYR154.O 39.34%
C:THR628.N-C:GLY639.O 39.34%
A:THR419.N-A:ARG256.O 39.34%
B:GLY608.N-B:GLN561.O 39.34%
C:PHE352.N-C:TYR327.O 39.34%
B:ASP1150.N-B:ILE1202.O 39.34%
A:THR1209.N-A:GLU1206.O 39.34%
A:ARG1172.N-A:TYR1165.O 39.34%
B:SER841.OG-B:SER837.O 39.34%
B:ALA988.N-B:ASN984.O 39.34%
A:GLY735.N-A:ILE743.O 39.34%
B:LEU77.N-B:ILE89.O 39.34%
B:TYR716.N-B:LEU709.O 39.34%
A:SER26.OG-A:TYR154.O 39.34%
A:SER36.OG-A:ASP34.O 39.34%
C:VAL415.N-C:TRP261.O 39.34%
B:ASN1012.N-B:THR1008.O 39.34%
B:TYR716.OH-B:GLY740.O 39.34%
C:ILE692.N-C:ALA685.O 39.34%
C:VAL684.N-C:TYR459.O 39.34%
C:PHE673.N-C:PHE664.O 39.34%
C:SER219.OG-C:GLY31.O 39.34%
A:ILE1063.N-A:VAL1059.O 39.34%
C:ILE39.N-C:ASN285.OD1 39.34%
A:ALA416.N-A:ARG297.O 39.34%
C:GLY608.N-C:GLN561.O 39.34%
B:TYR391.OH-B:ILE368.O 39.34%
A:GLU582.N-A:TYR544.O 39.34%
C:GLU582.N-C:TYR544.O 39.34%
412 11 SARS (SARS-CoV-1)
C:LEU709.N-C:TYR716.O 37.70% C:ILE105.N-C:VAL128.O 37.70%
C:SER879.N-C:ASP875.O 40.98% B:VAL400.N-B:VAL273.O 40.98%
C:THR195.N-C:ASN203.O 37.70% C:ASN426.N-C:ASN434.O 37.70%
A:VAL293.N-A:PHE275.O 44.26%
A:LEU30.N-A:SER26.O 44.26%
C:THR599.N-C:CYS567.O 42.62%
C:ILE340.N-C:LYS311.O 42.62%
A:VAL101.N-A:PHE132.O 45.90%
A:SER100.N-A:GLU94.O 45.90%
B:THR102.N-B:THR92.O 45.90%
A:THR930.N-A:MET926.O 45.90%
C:ASN1071.N-C:LEU1067.O 37.70% B:CYS737.N-B:SER741.O 37.70% A:LYS1094.N-A:LEU1090.O 37.70%
A:ARG1182.NH1-A:ASP1188.OD2 42.62%
B:ILE1147.N-B:TYR1155.O 42.62%
C:TYR391.OH-C:ILE368.O 42.62%
C:CYS351.N-C:GLY367.O 45.90%
A:CYS567.N-A:THR599.O 45.90%
B:ALA416.N-B:ARG297.O 45.90%
A:TYR385.N-A:VAL377.O 37.70% B:ARG297.N-B:ALA416.O 37.70% C:LEU1067.N-C:ILE1063.O 37.70%
A:SER145.N-A:THR148.O 42.62%
B:SER821.OG-B:ALA817.O 42.62%
B:LEU103.N-B:LEU130.O 42.62%
A:THR1209.OG1-A:GLU1206.O 45.90%
C:PHE579.N-C:LEU596.O 45.90%
B:GLU582.N-B:TYR544.O 45.90%
A:ILE340.N-A:LYS311.O 37.70%
B:THR405.N-B:SER312.O 37.70%
B:THR239.OG1-B:SER242.O 42.62%
B:ASN193.N-B:THR205.O 42.62%
B:ASN959.N-B:GLN955.O 45.90%
C:ARG1182.NH1-C:ASP1188.OD2 45.90%
C:LYS1100.N-C:ILE1095.O 37.70% B:ILE1115.N-B:THR1131.O 37.70%
A:ALA379.N-A:GLN383.O 42.62%
C:ALA1055.N-C:ASP1051.O 42.62%
B:LYS1094.N-B:LEU1090.O 45.90%
B:LEU1133.N-B:THR1113.O 45.90%
C:THR1006.OG1-C:GLU1002.O 37.70%
B:ILE353.N-B:THR364.O 37.70%
C:PHE317.N-C:VAL324.O 37.70%
A:THR1220.OG1-A:ASP1216.O 37.70%
B:MET926.N-B:ASP922.O 40.98%
B:LYS107.N-B:ASP125.O 44.26%
C:THR1136.N-C:ASN768.O 44.26%
C:ILE736.N-C:MET729.O 45.90%
C:THR826.OG1-C:ALA822.O 45.90%
B:LEU1134.N-B:THR770.O 37.70% B:ILE765.N-B:LYS1139.O 37.70% B:ARG1158.N-B:ASP1188.O 37.70%
B:PHE75.N-B:VAL91.O 40.98% B:SER767.N-B:ASP1137.O 40.98% B:SER26.OG-B:TYR154.O 40.98%
A:LYS1139.N-A:ILE765.O 44.26%
A:VAL186.N-A:GLY62.O 44.26%
C:THR826.N-C:ALA822.O 44.26%
C:SER821.OG-C:ALA817.O 45.90%
B:HIS78.N-B:LYS170.O 45.90%
C:LYS104.N-C:TYR90.O 37.70% B:ILE743.N-B:GLY735.O 37.70%
C:LEU251.N-C:VAL423.O 40.98% C:SER26.N-C:GLN29.OE1 40.98%
C:THR258.N-C:PHE417.O 37.70%
C:TYR90.N-C:LYS104.O 45.90%
C:ILE743.N-C:GLY735.O 44.26%
B:THR1006.OG1-B:GLU1002.O 44.26%
C:VAL1077.N-C:PHE1073.O 45.90%
B:PHE49.N-B:PHE183.O 45.90%
B:VAL427.N-B:GLY247.O 44.26%
B:LEU1067.N-B:ILE1063.O 44.26%
B:LEU662.N-B:TYR654.O 37.70% B:SER644.OG-A:LEU900.O 37.70%
B:LEU424.N-B:LEU436.O 40.98% C:ALA908.N-C:ASP904.O 40.98%
B:VAL377.N-B:TYR385.O 44.26%
B:SER428.N-B:ASN431.O 44.26%
B:PHE317.N-B:VAL324.O 47.54%
B:GLN433.N-B:ASN426.O 47.54%
C:VAL314.N-C:ASN403.O 45.90%
B:VAL423.N-B:LEU251.O 37.70%
C:ILE376.N-C:TYR298.O 40.98% A:VAL423.N-A:LEU251.O 40.98%
A:PHE487.N-A:ARG525.O 44.26%
C:ARG380.N-C:ASP294.O 44.26%
C:THR791.OG1-C:ASP788.OD2 47.54%
A:CYS737.N-A:SER741.O 47.54%
A:TYR391.OH-A:ILE368.O 45.90%
C:VAL324.N-C:PHE317.O 37.70% B:TYR391.N-B:PHE384.O 37.70% C:LEU1050.N-C:ILE1046.O 37.70%
C:LEU1133.N-C:THR1113.O 40.98% B:ILE606.N-B:PHE563.O 40.98% A:GLY608.N-A:GLN561.O 40.98%
C:ILE1192.N-C:GLY1154.O 44.26%
B:CYS1148.N-B:VAL1200.O 44.26%
C:ASP1150.N-C:ILE1202.O 44.26%
A:SER830.OG-A:THR826.O 47.54%
B:THR488.N-B:SER508.O 47.54%
C:LYS318.N-C:ALA399.O 47.54%
C:TYR544.N-C:GLU582.O 39.34%
C:TYR792.N-C:ASP788.O 39.34%
B:VAL1077.N-B:PHE1073.O 40.98% A:VAL881.N-A:LEU877.O 40.98%
B:GLN964.NE2-B:ALA962.O 44.26%
C:GLN964.N-C:ASN959.OD1 44.26%
C:VAL186.N-C:GLY62.O 47.54%
C:GLY735.N-C:ILE743.O 47.54%
B:LEU171.N-B:TYR58.O 39.34% A:LYS104.N-A:TYR90.O 39.34%
C:VAL40.N-C:VAL192.O 40.98% C:LYS444.N-C:SER440.O 40.98%
B:MET928.N-B:GLU924.O 44.26%
B:GLN774.N-B:HIS1130.O 44.26%
A:ALA583.N-A:THR591.O 47.54%
B:LEU300.N-B:ARG374.O 47.54%
Supplementary Information 413
B:VAL324.N-B:PHE317.O 34.43%
C:ILE524.N-C:ASN558.OD1 34.43%
C:LYS1094.N-C:LEU1090.O 37.70%
C:ILE765.N-C:LYS1139.O 37.70%
C:SER492.N-C:GLN504.O 31.15%
C:ALA977.N-C:LYS973.O 32.79%
B:SER492.N-B:GLN504.O 31.15%
B:TYR654.N-B:GLY663.O 31.15%
C:SER1121.N-C:GLU874.OE1 31.15% A:THR1064.OG1-A:ASP1060.O 31.15% C:LEU30.N-C:SER26.O 31.15% B:VAL1017.N-B:LYS1013.O 31.15% B:LYS1100.N-B:ILE1095.O 31.15%
A:THR791.OG1-A:ASP788.OD1 32.79% C:GLU825.N-C:SER821.O 32.79% A:ASN1096.ND2-A:GLN1092.O 32.79% B:ARG1182.NH1-B:ASP1188.OD2 32.79%
A:ARG1182.NH2-A:ASP1188.OD1 34.43%
C:SER355.N-C:VAL362.O 34.43%
B:THR599.N-B:CYS567.O 34.43%
B:PHE563.N-B:ILE606.O 34.43%
C:SER428.N-C:ASN431.O 36.07%
A:LEU804.N-A:CYS800.O 36.07%
C:VAL190.N-C:GLY42.O 36.07%
A:VAL684.N-A:TYR459.O 36.07%
C:ILE867.N-C:GLU924.OE1 31.15% A:SER1075.N-A:ASN1071.O 31.15%
A:VAL1200.N-A:GLY1146.O 32.79% B:VAL415.N-B:TRP261.O 32.79% C:THR1064.OG1-C:ASP1060.O 32.79%
B:ARG374.N-B:ASN387.OD1 34.43%
A:TYR792.N-A:ASP788.O 34.43%
B:ILE692.N-B:ALA685.O 34.43%
A:ILE692.N-A:ALA685.O 36.07%
B:ALA685.N-B:GLY693.O 36.07%
B:LEU824.N-B:LEU820.O 36.07%
A:CYS447.N-A:GLU443.O 31.15% B:SER172.N-B:ALA76.O 31.15%
C:TYR1155.N-C:ILE1147.O 32.79% B:ILE1063.N-B:VAL1059.O 32.79%
B:SER871.N-B:GLU874.OE1 34.43%
A:GLN964.N-A:ASN959.OD1 34.43%
B:PHE236.N-B:GLU375.OE1 36.07%
C:GLN253.N-C:VAL421.O 36.07%
B:VAL404.N-B:LEU266.O 31.15% A:GLU375.N-A:ASN387.OD1 31.15%
B:ILE736.N-B:MET729.O 32.79% B:SER871.N-B:GLU874.OE2 32.79% C:SER841.OG-C:SER837.O 32.79%
A:ALA76.N-A:SER172.O 34.43%
C:TYR777.OH-C:PRO1123.O 34.43%
B:THR1008.OG1-B:ILE1004.O 34.43%
C:TYR391.N-C:PHE384.O 36.07%
C:ILE606.N-C:PHE563.O 36.07%
C:LEU238.N-C:GLN253.OE1 36.07%
B:SER764.N-A:GLY941.O 31.15%
B:GLY869.N-B:GLN859.O 31.15% B:ASN985.N-B:LYS981.O 31.15%
C:TYR58.N-C:LEU171.O 32.79% A:THR826.N-A:ALA822.O 32.79%
B:THR791.OG1-B:ASP788.OD2 34.43%
C:ALA685.N-C:GLY693.O 34.43%
C:VAL273.N-C:VAL400.O 36.07%
C:SER523.OG-C:VAL609.O 36.07%
B:ASP1051.N-C:PRO551.O 31.15% C:THR696.OG1-C:ASP682.OD1 31.15%
C:THR897.OG1-A:ALA697.O 32.79% B:TYR65.N-B:LEU140.O 32.79%
B:ILE39.N-B:ASN285.OD1 34.43%
B:CYS794.N-B:ALA790.O 34.43%
C:ASN529.N-C:ALA489.O 36.07%
A:LEU394.N-A:GLY382.O 36.07%
A:SER1121.OG-A:GLU874.OE1 31.15% B:GLU398.N-B:LYS318.O 31.15%
B:HIS197.N-B:ARG200.O 32.79%
A:ALA1055.N-A:ASP1051.O 34.43%
A:THR239.OG1-A:SER242.O 34.43%
C:THR770.N-C:LEU1134.O 37.70%
C:LEU509.N-C:ASN512.O 36.07%
A:SER1030.N-A:ASN1026.O 32.79%
B:LEU1078.N-B:VAL1074.O 31.15%
A:ARG642.N-A:ILE674.O 32.79% A:ASN426.N-A:ASN434.O 32.79%
B:LEU394.N-B:GLY382.O 34.43%
B:ILE524.N-B:ASN558.OD1 34.43%
C:TYR716.N-C:LEU709.O 37.70%
A:SER658.OG-C:GLN909.OE1 37.70%
C:LEU300.N-C:ARG374.O 31.15% A:ARG250.NH2-A:ASP422.OD1 31.15%
C:ILE357.N-C:THR360.O 32.79%
B:THR319.N-B:TYR322.O 31.15%
A:SER355.OG-A:ASP323.O 32.79%
C:ARG1158.N-C:ASP1188.O 32.79% B:THR1220.OG1-B:ASP1216.O 32.79%
A:TYR777.OH-A:PRO1123.O 36.07%
C:PHE417.N-C:CYS259.O 36.07%
B:ASN354.N-B:LEU325.O 34.43%
A:TYR716.N-A:LEU709.O 37.70%
A:VAL1017.N-A:LYS1013.O 37.70%
B:PHE64.N-B:SER184.O 37.70%
C:LEU130.N-C:LEU103.O 31.15% B:THR1006.N-B:GLU1002.O 31.15%
C:THR1131.N-C:PHE1116.O 32.79% C:ILE1115.N-C:THR1131.O 32.79%
B:SER656.N-B:ASN660.O 36.07%
C:LEU394.N-C:GLY382.O 36.07%
A:ARG380.N-A:ASP294.O 37.70%
A:TYR58.N-A:LEU171.O 37.70%
A:LEU954.N-A:PHE950.O 31.15%
A:SER492.N-A:GLN504.O 37.70%
A:LYS665.N-A:ILE652.O 31.15%
B:SER989.OG-B:ASN985.O 32.79% A:SER871.N-A:GLU874.OE1 32.79%
C:GLN774.N-C:HIS1130.O 36.07%
C:ALA379.N-C:GLN383.O 36.07%
A:HIS1005.N-A:ALA1001.O 37.70%
Table 11.5 The HBs of MD of HCoV-NL63 spike trimer with occupancy rates ≥30% during the 651 μs’ MD (continuation 2)
414 11 SARS (SARS-CoV-1)
B:LEU709.N-B:TYR716.O 32.79% A:ILE397.N-A:ARG380.O 32.79% B:SER895.OG-B:ASP892.OD2 32.79% A:TYR88.N-A:CYS106.O 32.79%
C:LEU824.N-C:LEU820.O 32.79% B:GLN683.NE2-B:SER460.OG 32.79%
A:TYR633.N-A:VAL474.O 31.15% C:ALA1068.N-C:THR1064.O 31.15% B:SER741.OG-B:ASP739.OD1 31.15% B:SER830.OG-B:THR826.O 31.15% C:ALA976.N-C:GLN972.O 31.15% A:ALA977.N-A:LYS973.O 31.15%
A:THR826.OG1-A:ALA822.O 34.43% B:SER1121.OG-B:GLU874.OE1 34.43% C:SER871.N-C:GLU874.OE2 34.43% A:SER767.N-A:ASP1137.O 34.43% A:ALA956.N-A:LEU952.O 34.43% C:THR405.N-C:SER312.O 34.43% B:LEU257.N-B:GLY224.O 34.43% B:LEU251.N-B:VAL423.O 34.43% B:VAL793.N-B:CYS789.O 34.43% A:SER772.N-A:VAL1132.O 34.43% C:ILE353.N-C:THR364.O 34.43% C:ILE1063.N-C:VAL1059.O 34.43% C:HIS197.N-C:ARG200.O 34.43% C:ALA76.N-C:SER172.O 34.43% A:LYS107.N-A:ASP125.O 34.43% B:PHE840.N-B:ASP836.O 34.43% A:THR760.OG1-A:THR1198.O 34.43% C:THR488.N-C:SER508.O 34.43% A:GLN253.N-A:VAL421.O 34.43% B:GLN253.N-B:VAL421.O 34.43% B:GLN706.N-B:SER718.O 34.43% B:LEU820.N-B:ASP816.O 34.43% A:PHE579.N-A:LEU596.O 34.43% B:ALA379.N-B:GLN383.O 34.43% B:GLN683.N-B:MET695.O 34.43% B:LEU130.N-B:LEU103.O 34.43% B:VAL881.N-B:LEU877.O 34.43% C:ASN401.N-C:VAL316.O 34.43% C:TYR526.OH-C:ILE543.O 32.79% B:ILE397.N-B:ARG380.O 32.79% B:THR628.N-B:GLY639.O 32.79% C:LEU662.N-C:TYR654.O 32.79% A:LYS812.N-A:THR808.O 32.79% A:ALA60.N-A:THR169.O 32.79% A:THR696.N-A:TYR715.O 32.79% A:VAL1077.N-A:PHE1073.O 32.79% C:LEU103.N-C:LEU130.O 32.79% C:ARG1085.NE-C:GLU825.OE2 32.79% A:THR1008.OG1-A:ILE1004.O 32.79% A:LEU1126.N-A:LEU778.O 32.79%
A:ARG1088.N-A:VAL1084.O 36.07%
B:SER1121.OG-B:GLU874.OE2 36.07%
B:ASP875.N-B:SER871.O 36.07%
A:ARG1105.NH1-A:GLU1097.OE1 36.07%
B:THR770.N-B:LEU1134.O 36.07%
A:THR1136.N-A:ASN768.O 36.07%
C:ILE1147.N-C:TYR1155.O 36.07%
C:LEU596.N-C:PHE579.O 36.07%
B:TYR597.N-B:SER569.O 36.07%
A:LEU596.N-A:PHE579.O 36.07%
A:SER656.N-A:ASN660.O 36.07%
B:SER1030.N-B:ASN1026.O 36.07%
B:ALA908.N-B:ASP904.O 36.07%
C:PHE64.N-C:SER184.O 36.07%
C:HIS152.N-C:GLY141.O 36.07%
A:ILE105.N-A:VAL128.O 36.07%
B:ILE105.N-B:VAL128.O 36.07%
A:THR92.OG1-A:SER73.O 36.07%
B:ILE780.N-B:ASP1124.O 36.07%
C:LEU1126.N-C:LEU778.O 36.07%
C:SER1121.OG-C:GLU874.OE1 36.07%
A:SER871.N-A:GLU874.OE2 36.07%
A:THR488.N-A:SER508.O 36.07%
B:LEU596.N-B:PHE579.O 36.07%
C:ASN387.N-C:GLU375.O 36.07%
A:HIS197.N-A:ARG200.O 36.07%
B:THR195.N-B:ASN203.O 36.07%
C:TYR792.OH-C:ARG1066.O 36.07%
C:VAL101.N-C:PHE132.O 36.07%
C:ILE780.N-C:ASP1124.O 36.07%
B:ILE1009.N-B:HIS1005.O 36.07%
A:MET926.N-A:ASP922.O 36.07%
B:VAL993.N-B:SER989.O 36.07%
A:SER1121.OG-A:GLU874.OE2 36.07%
C:ILE1118.N-C:LEU1129.O 36.07%
A:ILE1147.N-A:TYR1155.O 36.07%
B:TYR544.N-B:GLU582.O 36.07%
A:ILE353.N-A:THR364.O 36.07%
B:THR1029.N-B:LEU1025.O 36.07%
B:ILE66.N-B:VAL182.O 36.07%
A:ARG225.NH2-A:GLU443.OE2 31.15%
A:THR196.N-A:SER36.O 31.15%
B:SER547.OG-A:ASP1051.OD2 31.15%
A:ASN959.N-A:GLN955.O 31.15%
B:ALA976.N-B:GLN972.O 31.15%
A:ILE1118.N-A:LEU1129.O 31.15%
A:ASN1120.N-A:LEU1127.O 31.15%
A:VAL1007.N-A:ALA1003.O 31.15%
B:SER100.N-B:GLU94.O 31.15%
C:ILE66.N-C:VAL182.O 31.15%
C:THR791.OG1-C:ASP788.OD1 31.15%
B:ARG225.NH2-B:GLU443.OE1 31.15%
A:ASN666.N-A:ASN671.O 31.15%
B:PHE568.N-B:VAL515.O 31.15%
A:LYS318.N-A:ALA399.O 31.15%
C:PHE568.N-C:VAL515.O 31.15%
C:ARG1176.N-C:ASN1161.O 31.15%
B:ILE1118.N-B:LEU1129.O 31.15%
C:ALA99.N-C:GLU134.O 31.15%
B:ILE357.N-B:THR360.O 31.15%
C:ASN506.N-C:THR490.O 31.15%
C:VAL881.N-C:LEU877.O 32.79%
A:LEU424.N-A:LEU436.O 32.79%
A:THR258.N-A:PHE417.O 32.79%
B:LYS1139.N-B:ILE765.O 32.79%
A:THR770.N-A:LEU1134.O 32.79%
A:PHE840.N-A:ASP836.O 32.79%
B:SER329.N-B:TYR350.O 32.79%
C:ARG642.N-C:ILE674.O 32.79%
C:ILE89.N-C:LEU77.O 34.43%
B:TYR777.OH-B:PRO1123.O 36.07% A:SER329.N-A:TYR350.O 31.15%
Supplementary Information 415
416 Table 11.6 The HBs with more than 50% occupancy rates during the 10 μs’ MD simulations for the 2AJF model of [321]
11 SARS (SARS-CoV-1) Donor
Acceptor
Occupancy
A:THR229.OG1
A:ASP225.O
67.99%
A:ARG357.NH1
A:ASP355.OD2
64.24%
E:THR486.OG1
A:ASP355.OD2
64.01%
A:THR282.OG1
A:LEU278.O
62.63%
A:THR567.OG1
A:TYR215.O
60.17%
E:ARG441.N
E:ASN409.OD1
59.90%
A:TYR237.OH
A:VAL485.O
58.87%
A:SER331.OG
A:PHE327.O
58.87%
A:HIS241.N
A:TYR237.O
58.79%
A:ARG357.NE
A:ASP355.OD1
57.47%
A:TYR127.OH
A:SER502.O
57.05%
A:PHE464.N
A:ARG460.O
56.40%
E:THR425.OG1
E:ASP429.OD2
56.15%
E:ARG495.NE
E:ASP429.OD2
56.12%
A:SER317.OG
A:LYS313.O
55.86%
A:TRP461.N
A:GLU457.O
55.76%
E:TYR438.OH
E:ASP429.OD1
55.49%
A:THR129.OG1
A:THR125.O
55.06%
E:VAL420.N
E:LYS365.O
54.18%
A:THR371.OG1
A:ASP367.O
54.05%
A:THR125.OG1
A:ASN121.O
53.52%
A:LEU359.N
A:THR347.O
53.49%
A:GLU375.N
A:THR371.O
52.67%
A:THR122.OG1
A:THR118.O
52.65%
A:TYR516.OH
A:THR229.OG1
52.12%
E:ARG495.NH2
E:ASP429.OD1
51.34%
A:MET383.N
A:ILE379.O
50.92%
A:GLU238.N
A:LYS234.O
50.69%
A:THR27.OG1
A:GLU23.O
50.57%
Chapter 12
MERS-Coronavirus (MERS)
Abstract This chapter briefly presents some structural bioinformatics about MERS-CoV binding with human ACE2. We find in the middle of interactions there are several hydrogen bonds and salt bridges linking the monomeric MERSCoV spike and the human ACE2 and hydrophobic core linking the beginning several residues of human ACE2 and the residues GLU513, PRO515, and VAL555 of the spike. Keywords CoV · MERS-CoV · Monomeric spike · Binding human ACE2 · Optimization and MD studies
12.1 Introduction Coronaviruses belong to the Beta genus. Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a novel coronavirus (Middle East respiratory syndrome coronavirus or MERS-CoV) that was first identified in Saudi Arabia in 2012. Although most of human cases of MERS-CoV infections have been attributed to human-to-human infections in healthcare settings, current scientific evidence suggests that dromedary camels are a major reservoir host for MERS-CoV and an animal source of MERS infection in humans. However, the exact role of dromedaries in the transmission of the virus and the exact route(s) of transmission are unknown. The emergence and persistence of MERS-CoV, almost one decade by now, highlight the need for the rapid development of effective interventions against this highly pathogenic coronavirus (CoV). Structural MD studies related to MERSCoV infection process are limited. Our structural bioinformatics presented in this chapter should be useful to the interventions against MERS-CoV.
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_12
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418
12 MERS-Coronavirus (MERS)
12.2 Materials and Methods 5x5c.pdb is the prefusion structure of MERS-CoV spike glycoprotein [396], the structure has ABC chains, and each chain has residues TYR18-ALA1206; in the structure, there are two states of the RBD with receptor-binding region either buried (lying state) or exposed (standing state) – demonstrating an inherently flexible RBD readily recognized by the receptor. A MERS-human ACE2 binding model was built by Rynkiewicz et al. at website https://people.rit.edu/gabsbi. The model has two chains: A chain aa SER1-ASP597 is the human ACE2, and B chain aa VAL598LEU805 is the MERS-CoV spike monomer aa VAL381-LEU588. This chapter is to optimize this model and then present some basic structural bioinformatics for MERS binding human ACE2.
12.3 New Structural Bioinformatics We optimized the model with RMSD value 0.559261 Å. In the optimized model, there are seven .π -cations TYR197-LYS559.NZ+, TYR261-LYS423.NZ+, PHE574LYS578.NZ+, TRP147-ARG151.NH2+, TRP284-ARG288.NH2+, TYR497-ARG255.NH2+, and TRP443-ARG186.NH2+ in A chain and three .π -.π stackings TYR686-PHE616, PHE621PHE602, and PHE788-PHE635 in B chain. Tables 12.1 and 12.2 listed all the HBs and
SBs of the optimized model; the HB A:ASP12.OD2-B:LYS719.NZ and the SB A:ASP12-B:LYS719 link A chain and B chain of the model optimized (Fig. 12.1); there are also another two HBs A:LYS13.NZ-B:GLY755.O and B:LYS719.NZA:THR9.OG1 linking AB chains (Fig. 12.1). We also find there is a hydrophobic core/hole between B chain and A chain constructed by residues VAL772-PRO732GLU730 of B chain spike and residues SER1-GLU5-THR9 of A chain human ACE2 (Fig. 12.1). In order to agree with the residue numbers of 5x5c.pdb, we should subtract 217 from B chain residue numbers.
Fig. 12.1 There is a hydrophobic core/hole between B chain and A chain constructed by residues VAL772-PRO732-GLU730 of B chain MERS spike monomer and residues SER1-GLU5-THR9 of A chain human ACE2. The HBs A:ASP12.OD2-B:LYS719.NZ-A:THR9.OG1, B:GLY755.OA:LYS13.NZ, and SB A:ASP12-B:LYS719 are in the middle of the contacts between B chain and A chain
During viral membrane fusion with the cell membrane, the virus spike S2 protein arranges in a coiled coil with its HR2 domain packed into a deep groove on HR1. The MD of MERS-CoV is done in [164]; the MD simulations were carried out for MERS-CoV heptad repeat domains (HRs, PDB entries 4MOD and 4NJL) HR
12.4 Concluding Remarks
419
trimer, S2 monomer, and S2 trimer. Fluctuation of HR residue positions revealed major changes in the C-terminal of HR2 and the linker coil between HR1 and HR2 in both monomer and trimer [164]. Hydrophobic residues at the a and d positions of HR helices stabilize the whole system [164]. In [7], the author explored structural dynamics of the MERS-CoV receptor DPP4 and mutant DPP4 receptors. Mouse DPP4 (mDPP4) receptor is not a functional receptor for MERS-CoV, while human DPP4 (hDPP4) is. The variability of DPP4 receptors against MERS-CoV is not fully investigated, especially conformational and structural differences. Therefore, investigating the conformational differences of the DPP4 receptors can aid in developing new small animal models for MERSCoV vaccines and antiviral agent evaluation. In [7], the author used MD simulations and docking techniques to investigate these structural differences in DPP4 receptors, and results showed chimeric mouse mDPP4 (cmDPP4) has a similar compact conformation as the wild-type hDPP4 based on the structural analysis. Interestingly, a single THR288ALA mutation induced a relaxed conformation in chimeric 2 hDPP4 (c2hDPP4) and chimeric 2 mDPP4 (c2mDPP4) [7]; in addition to its significant effect on the DPP4 flexibility, the THR288 residue is known for its critical function in MERS-CoV RBD interaction. Moreover, MERS-CoV RBD adopts a “standing” conformation when docked to hDPP4 and cmDPP4 in blade IV and V regions [7].
12.4 Concluding Remarks We optimized a model of MERS-CoV monomeric spike binding with human ACE2. In the optimized model, we found seven .π -cations TYR197-LYS559.NZ+, TYR261LYS423.NZ+, PHE574-LYS578.NZ+, TRP147-ARG151.NH2+, TRP284-ARG288.NH2+, TYR497-ARG255.NH2+, and TRP443-ARG186.NH2+ in human ACE2 and three .π -.π stackings TYR686-PHE616, PHE621-PHE602, and PHE788-PHE635 in the MERS spike;
the HB A:ASP12.OD2-B:LYS719.NZ and the SB A:ASP12-B:LYS719 link A chain human ACE2 and B chain MERS spike of the model optimized; there are also another two HBs A:LYS13.NZ-B:GLY755.O and B:LYS719.NZ-A:THR9.OG1 linking AB chains; we also found there is a hydrophobic core/hole between B chain and A chain constructed by residues VAL772-PRO732-GLU730 of B chain spike and residues SER1-GLU5-THR9 of A chain human ACE2. Brief reviews on MDs of MERS-CoV spike HR, S2 [164] and MERS-CoV receptor DPP4 [7] are done in this chapter.
A:SER52.OG-A:GLY48.O
A:LEU438.N-A:PHE434.O
A:ASP579.OD1-A:LYS582.NZ
A:CYS512.N-A:GLN508.O
A:ARG151.NE-A:ASP481.OD1
A:ARG151.NH1-A:ASP481.OD2
A:GLN58.N-A:PHE54.O
A:GLN58.NE2-A:GLU57.OE2
A:ARG255.N-A:ASP251.OD2
A:ARG288.N-A:ASP285.OD1
A:LYS229.NZ-A:LEU263.O
A:THR100.OG1-A:LYS96.O
A:THR37.OG1-A:ASN40.OD1
A:LYS457.NZ-A:GLU461.OE2
A:GLU220.N-A:LYS216.O
A:GLU292.OE2-A:LYS295.NZ
A:GLU294.OE1-A:LYS291.NZ
A:ASN103.ND2-A:ASN99.O
A:ASN116.N-A:GLU122.O
A:ASN116.ND2-A:GLU122.OE1
A:THR478.OG1-A:ASP476.OD2 A:THR501.OG1-A:TYR497.O
A:LYS94.NZ-A:GLU171.OE1 A:MET105.N-A:ILE101.O
A:LYS96.NZ-A:ASP93.OD2
A:TRP253.N-A:ASP251.OD1
A:TRP145.N-A:ASN141.O
A:THR9.OG1-A:GLU5.O
A:THR549.OG1-A:TYR197.O
A:LYS578.NZ-A:GLU571.OE2 A:LYS582.NZ-A:ASP579.OD1 A:LYS8.NZ-A:GLU5.OE2
A:GLU164.OE2-A:ARG97.NE
A:GLU179.N-A:ASP183.OD2
A:GLU214.OE2-A:ARG564.NH2
A:ARG564.NH2-A:GLU214.OE2
A:THR478.N-A:ASP476.OD2
A:THR435.OG1-A:THR431.O
A:THR396.OG1-A:SER393.O
A:THR344.OG1-A:LEU315.O
A:ARG97.NE-A:GLU164.OE2
A:LYS578.N-A:PHE574.O
A:LYS523.NZ-A:GLU417.OE2
A:LYS516.NZ-A:ALA514.O
A:LYS423.NZ-A:ILE273.O
A:ARG97.NH1-A:GLU164.OE1
A:GLU164.N-A:PRO160.O
A:GLU164.OE1-A:ARG97.NH1
A:ARG564.NH1-A:ASN562.OD1
A:ARG564.NH1-A:GLU214.OE1
A:GLU163.N-A:ARG159.O
A:GLU163.OE1-A:ARG159.NE
A:THR347.OG1-A:ASP350.OD2 A:THR353.OG1-A:ASP349.O
A:LYS447.NZ-A:GLU179.OE1 A:LYS457.N-A:GLU477.OE2
A:GLU148.N-A:LEU144.O
A:GLU153.N-A:SER149.O
A:ARG464.NH1-A:THR590.O
A:ARG464.NH2-A:GLU471.OE2
A:ARG500.N-A:ARG496.O
A:THR347.N-A:ASP350.OD2
A:LYS440.N-A:TYR436.O
A:GLU122.N-A:ASN119.O
A:GLU142.N-A:ASP139.OD2
A:ARG375.NH2-A:ALA368.O
A:ARG464.N-A:TRP460.O
A:ARG541.NE-A:ASN538.O
A:THR306.OG1-A:GLY336.O A:THR329.N-A:LEU341.O A:THR34.OG1-A:TRP30.O
A:LYS345.NZ-A:ASP317.OD2 A:LYS398.NZ-A:ASP525.O A:LYS423.NZ-A:ASP274.OD2
A:GLN580.N-A:TRP576.O
A:GLN580.NE2-A:ASP579.OD2
A:GLN63.NE2-A:ASN85.OD1
A:ARG339.NE-A:ASP337.OD1
A:THR276.OG1-A:ASP274.OD1
A:THR276.N-A:ASP274.OD1
A:THR264.N-A:LEU260.O
A:THR211.N-A:ASP207.O
A:THR107.OG1-A:ASN103.O
A:THR107.N-A:ASN103.O
A:THR104.OG1-A:THR100.O
A:LYS345.N-A:ASP350.OD1
A:LYS335.NZ-A:ASP20.OD1
A:LYS335.N-A:GLU19.OE2
A:LYS295.NZ-A:GLU292.OE2
A:LYS291.NZ-A:GLU294.OE1
A:LYS270.NZ-A:GLU415.OE1
A:LYS270.NZ-A:ASP413.OD2
A:ARG339.NH1-A:ASP337.OD2
A:ARG339.N-A:TRP331.O
A:GLN454.NE2-A:ASP453.OD2
A:GLN504.N-A:ARG500.O
A:ARG201.NH1-A:GLU190.OE1
A:ARG201.NH2-A:ASP183.OD2
A:GLN370.NE2-A:ARG541.O
A:GLN411.NE2-A:ASP413.OD1
A:ARG186.NH2-A:ASP180.OD1
A:ARG201.NE-A:ASP183.OD1
A:GLN362.NE2-A:PRO303.O
A:GLN370.N-A:TYR367.O
A:ARG174.NH2-A:GLU179.O
A:ARG186.N-A:GLY182.O
A:SER593.OG-A:TRP592.O
A:SER589.OG-A:ASP591.OD2
A:LYS216.N-A:PHE212.O
A:LYS169.NZ-A:ASP491.OD2
A:GLN307.NE2-A:GLU311.OE1
A:GLN322.NE2-A:THR34.O
A:ARG159.NH1-A:LYS452.O
A:ARG159.NH2-A:GLU477.OE1
A:SER527.OG-A:ASP525.OD2 A:SER529.OG-A:GLU531.OE1 A:SER589.N-A:ILE241.O
A:LYS13.NZ-A:GLU17.OE2 A:LYS13.NZ-B:GLY755.O A:LYS169.N-A:TYR165.O
A:GLN24.N-A:ASP20.O
A:GLN24.NE2-A:ASP20.OD2
A:GLN287.N-A:ASP285.OD2
A:ARG159.NE-A:GLU163.OE1
A:SER527.N-A:ASP525.OD2
A:SER407.OG-A:ASP409.OD1
A:LEU79.N-A:VAL75.O
A:LEU374.N-A:PRO371.O
A:ARG159.NH1-A:GLU163.OE2
A:ARG151.NH2-A:TRP147.O
A:SER493.OG-A:GLU380.OE2
A:LEU421.N-A:GLU417.O
A:ASP49.N-A:ASN45.O
A:ASP491.OD2-A:LYS169.NZ
A:ARG143.NH1-A:ALA135.O
A:SER393.OG-A:GLN508.OE1 A:SER402.OG-A:LYS398.O
A:ARG143.NH1-A:SER137.O
A:LEU341.N-A:THR329.O A:LEU352.N-A:MET348.O
A:ASP413.OD2-A:LYS270.NZ
A:ASP481.OD1-A:ARG151.NE
A:ALA510.N-A:GLN506.O
A:SER391.OG-A:GLU388.O
A:ALA7.N-A:ILE3.O
A:LEU27.N-A:TYR23.O
A:SER299.OG-A:PHE296.O
A:ASP207.N-A:GLN203.O
A:ASP274.OD2-A:LYS423.NZ
A:ALA246.N-A:VAL470.O
A:ALA278.N-A:ASP277.OD1
A:LEU244.N-A:GLY468.O
A:SER152.OG-A:GLU148.OE2 A:SER26.N-A:PHE22.O
A:ALA224.N-A:GLU220.O
A:ILE418.N-A:ASN414.O A:ILE428.N-A:GLN424.O
A:ASP12.OD2-B:LYS719.NZ
A:ASP20.OD1-A:LYS335.NZ
A:ALA18.N-A:PHE14.O
Table 12.1 The HBs of the optimized MERS ACE2 binding model A:TYR479.OH-A:GLU148.OE2
B:LEU660.N-B:LEU619.O
B:LEU619.N-B:LEU660.O
B:ILE790.N-B:CYS695.O
B:ILE717.N-B:ASN685.OD1
B:ILE697.N-B:PHE788.O
B:ILE659.N-B:THR791.O
B:ILE650.N-B:SER646.O
B:HIS703.NE2-B:GLU782.OE1
B:GLY789.N-B:ASP661.O
B:GLY787.N-B:PHE663.O
B:GLY775.N-B:ASP756.O
B:GLU766.OE1-B:LYS760.NZ
B:GLU599.OE2-B:LYS630.NZ
B:GLU599.OE1-B:LYS804.NZ
B:GLN793.N-B:SER657.O
B:GLN733.N-B:CYS720.O
B:GLN688.NE2-B:CYS695.O
B:GLN612.NE2-B:THR750.OG1
B:CYS695.N-B:ILE790.O
B:ASP661.OD2-B:ARG618.NE
B:ASP661.N-B:GLY789.O
B:ASN718.ND2-B:SER776.OG
B:ASN692.ND2-B:SER689.OG
B:ASN638.N-B:LEU698.O
B:ASN625.ND2-B:PRO803.O
B:ARG722.NH2-B:GLY767.O
B:ARG722.NE-B:LEU724.O
B:ARG618.NH2-B:ASP661.OD1
B:ARG618.NE-B:ASP661.OD2
B:ALA773.N-B:TYR758.O
B:ALA699.N-B:MET786.O
A:VAL469.N-A:LYS463.O
A:VAL321.N-A:ASN320.OD1
A:VAL226.N-A:LEU222.O
A:VAL194.N-A:ASP198.OD1
A:TYR569.OH-A:GLN424.OE1
A:TYR503.N-A:THR499.O
A:TYR498.OH-A:VAL208.O
A:TYR497.OH-A:GLU384.OE1
B:PHE788.N-B:ILE697.O
B:TYR758.N-B:ALA773.O
B:TYR740.OH-B:PHE616.O
B:TYR716.N-B:SER776.O
B:TYR714.OH-B:THR781.OG1
B:TYR714.N-B:VAL778.O
B:TYR686.OH-B:ASP661.OD1
B:TYR665.OH-B:MET669.O
B:TYR665.N-B:GLN785.O
B:TYR662.OH-B:PRO604.O
B:TYR662.N-B:LYS617.O
B:TYR626.OH-B:ALA651.O
B:TYR614.OH-B:PRO748.O
B:TRP752.N-B:ASP756.OD2
B:THR791.N-B:ILE659.O
B:THR781.OG1-B:GLN783.O
B:THR777.OG1-B:ASP754.OD2
B:THR707.OG1-B:LEU606.O
B:THR700.OG1-B:ASN638.OD1
B:THR700.N-B:SER636.O
B:THR694.OG1-B:GLN688.OE1
B:THR694.N-B:SER643.O
B:THR641.N-B:LEU696.O
B:THR609.OG1-B:THR709.OG1
B:SER776.N-B:TYR716.O
B:SER763.OG-B:GLU766.OE2
B:SER763.N-B:GLU766.OE2
B:SER745.OG-B:PRO742.O
B:SER725.N-B:ASP727.OD2
B:SER682.OG-B:SER677.OG
B:SER677.OG-B:SER674.O
B:SER671.OG-B:ASP672.OD2
B:SER664.N-B:PRO611.O
B:SER656.OG-B:GLY795.O
B:SER652.OG-B:ALA648.O
B:SER643.N-B:THR694.O
B:SER636.N-B:THR700.O
B:SER633.N-B:THR629.O
B:SER603.OG-B:ASP601.OD1
B:SER603.N-B:ASP601.OD1
420 12 MERS-Coronavirus (MERS)
A:TRP548.NE1-A:TYR189.O A:TYR165.OH-A:ASP491.OD1 A:TYR178.N-A:ALA173.O
A:PHE267.N-A:ASN419.OD1 A:PHE290.N-A:ALA286.O A:TYR199.OH-A:ASP207.OD2
A:ILE403.N-A:HIS399.O
A:ASP12.N-A:LYS8.O
A:TYR436.OH-A:GLU209.OE2
A:SER149.N-A:TRP145.O
A:TYR367.N-A:TYR363.O A:TYR367.OH-A:ASP364.OD1
A:SER137.OG-A:GLU142.OE1
A:SER110.OG-A:SER106.O
A:ILE289.N-A:ASP285.O
A:ILE36.N-A:LYS323.O
A:ASN72.N-A:GLU4.OE2
A:TYR261.N-A:THR258.O A:TYR261.OH-A:ASN272.OD1
A:PHE570.N-A:LEU566.O A:PHE574.N-A:PHE570.O
A:HIS399.ND1-A:ASP525.OD1
A:ILE101.N-A:ARG97.O
A:ASN568.ND2-A:GLU509.OE2
A:ASN581.N-A:LEU577.O
A:ASN85.ND2-A:ASN176.OD1
A:TYR225.N-A:HIS221.O A:TYR23.OH-A:ASP337.OD2
A:PHE537.N-A:GLY533.O A:PHE54.N-A:LYS50.O
A:HIS223.N-A:TYR219.O
A:HIS223.NE2-A:GLY468.O
A:ASN560.ND2-A:ASP207.OD1
A:ASN568.N-A:ARG564.O
A:TYR219.OH-A:VAL467.O
A:PHE446.N-A:ARG442.O A:PHE507.N-A:TYR503.O
A:HIS16.ND1-A:ASP12.O
A:HIS210.N-A:GLU206.O
A:ASN490.ND2-A:PHE486.O
A:ASN554.ND2-A:LEU550.O
A:TYR197.OH-A:GLU553.OE1
A:PHE420.N-A:THR416.O
A:GLY196.N-A:ASP198.OD2
A:GLY254.N-A:ASP251.OD1
A:GLY334.N-A:ASP332.OD1
A:ASN419.N-A:GLU415.O
A:ASN419.ND2-A:PHE267.O
A:ASN45.N-A:VAL41.O
A:TRP592.NE1-A:ASP597.OD1
A:PHE14.N-A:PHE10.O A:PHE256.N-A:ASP251.OD2
A:GLU5.OE2-A:LYS8.NZ
A:GLU571.N-A:LEU567.O
A:ASN31.N-A:LEU27.O
A:ASN33.N-A:SER29.O
B:LEU762.N-B:GLY769.O
A:TRP331.N-A:ARG339.O A:TRP443.N-A:GLU439.O
A:MET365.N-A:ILE361.O A:MET437.N-A:PRO433.O
A:GLU471.N-A:GLU471.OE1
A:GLU471.OE2-A:ARG464.NH2
A:ASN170.ND2-A:VAL166.O
A:ASN232.ND2-A:ALA228.O
B:LEU705.N-B:PRO702.O
A:TRP30.N-A:SER26.O A:TRP310.NE1-A:GLU294.OE2
A:MET342.N-A:MET314.O A:MET348.N-A:THR276.OG1
A:GLU380.N-A:ASP188.OD2
A:GLU461.N-A:LYS457.O
A:ASN136.ND2-A:GLU132.OE2
B:LEU667.N-B:GLN785.OE1
B:PHE621.N-B:LEU658.O
B:MET786.N-B:ALA699.O
B:LYS804.NZ-B:GLU599.OE1
B:LYS760.NZ-B:GLU766.OE1
B:LYS760.N-B:LEU771.O
B:LYS719.NZ-A:THR9.OG1
B:LYS719.NZ-A:ASP12.OD2
B:LYS713.NZ-B:TRP752.O
B:LYS710.NZ-B:GLU782.O
B:LYS670.NZ-B:ASP639.OD1
B:LYS630.NZ-B:GLU599.OE2
B:LYS630.N-B:ASN627.OD1
B:LYS617.NZ-B:TYR662.OH
B:LYS617.NZ-B:THR609.O
B:LEU771.N-B:LYS760.O
B:LEU698.N-B:ASP639.O
B:LEU696.N-B:THR641.O
A:ASN15.N-A:LEU11.O
A:TRP257.NE1-A:GLY254.O A:TRP284.N-A:MET279.O
A:MET134.N-A:LEU130.O A:MET305.N-A:GLU294.OE2
A:GLU357.N-A:THR353.O
A:GLU38.N-A:GLU38.OE2
A:ASN119.ND2-A:GLU122.OE1
A:ASN136.N-A:GLU132.O
B:TYR758.OH-B:ASP756.OD2
B:VAL772.N-B:SER721.O
B:VAL751.N-B:SER715.OG
B:VAL735.N-B:GLN683.O
B:VAL701.N-B:LEU784.O
B:TYR794.OH-B:GLN644.OE1
12.4 Concluding Remarks 421
422 Table 12.2 The SBs of the optimized MERS ACE2 binding model
12 MERS-Coronavirus (MERS) In A chain
In B chain
Linking A-B chains
ASP20-LYS335
ASP639-LYS670
A:ASP12-B:LYS719
ASP93-LYS96
ASP661-ARG618
ASP180-ARG186
GLU599-LYS630
ASP183-ARG201
GLU599-LYS804
ASP188-LYS544
GLU753-LYS713
ASP274-LYS423
GLU766-LYS760
ASP317-LYS345
GLU782-HIS703
ASP337-ARG339
GLU782-LYS710
ASP364-HIS383 ASP413-LYS270 ASP481-ARG151 ASP491-LYS169 ASP525-HIS399 ASP579-LYS582 GLU4-LYS8 GLU5-LYS8 GLU17-LYS13 GLU19-ARG375 GLU163-ARG159 GLU164-ARG97 GLU171-LYS94 GLU179-LYS447 GLU190-ARG201 GLU209-LYS440 GLU214-ARG564 GLU220-HIS221 GLU292-ARG288 GLU292-LYS295 GLU294-LYS291 GLU357-HIS360 GLU380-ARG496 GLU384-HIS356 GLU388-ARG500 GLU412-LYS401 GLU415-LYS270 GLU417-HIS522 GLU417-LYS523 GLU439-ARG442 GLU461-LYS457 GLU465-LYS216 GLU471-ARG464 GLU477-ARG159 GLU531-LYS516 GLU571-LYS578
Chapter 13
Human ACE2, Human IL6, Human IL6R, and Human nAChRs
Abstract SARS-CoV-2, the virus causing the COVID-19 global pandemic, encodes for a trimeric spike glycoprotein that contains a receptor-binding domain (RBD) that binds favorably to the ACE2 (angiotensin-converting enzyme 2) receptor present on the surface of human host cell. There is some early evidence that human interleukin 6 (human IL6) can be used as an inflammatory marker for severe COVID-19 infection with poor prognosis. Human IL6R is the IL6 receptor that has been shown to interact with IL6 and ciliary neurotrophic factor. This short chapter is to study human ACE2, human IL6, and human IL6R from optimization and molecular dynamics (MD) point of view to present some basic structural bioinformatics of them. The studies are fundamentally important in the fight against SARS-CoV-2. Human .α4β2-, .α7-, and .αβγ δ-nAChRs binding SARS-CoV-2 spike Y674-R685 region are also studied in this chapter. Keywords COVID-19 · Human ACE2 · Human IL6 · Human IL6R · Molecular structure optimization and molecular dynamics (MD) studies
13.1 Introduction SARS-CoV-2, the virus causing the COVID-19 global pandemic, encodes for a trimeric spike glycoprotein that contains a receptor-binding domain (RBD) that binds favorably to the ACE2 (angiotensin-converting enzyme 2) receptor present on the surface of human throat cells and lung epithelial cells. The receptor-binding motif (S438-Q506 region) of SARS-CoV-2 spike is known to bind to ACE2. This binding creates a fusion between the human cell membrane and the spike protein, allowing the viral genetic material to be replicated within the human host cell. Therefore, understanding the interaction of the spike with ACE2 at the cell surface is fundamentally important in the fight against SARS-CoV-2. There is some early evidence that interleukin 6 (IL6) can be used as an inflammatory marker for severe COVID-19 infection with poor prognosis, in the content of the wider coronavirus pandemic. IL6 is responsible for stimulating acute phase protein synthesis. It © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_13
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supports the growth of B cells and is antagonistic to regulatory T cells. Human IL6R is the IL6 receptor that has been shown to interact with IL6 and ciliary neurotrophic factor. Human IL6R is a protein complex consisting of an IL6 receptor subunit (IL6R) and interleukin 6 signal transducer glycoprotein 130. This brief chapter is to introduce some basic structural bioinformatics of human ACE2, human IL6, and human IL6R through our optimization and MD technologies.
13.2 Materials and Methods We got the human ACE2 monomer (6LZG.pdb, aa SER19-ALA614) 664 .μs, human IL6 monomer (1ALU.pdb, aa LEU19-MET184) 1593 .μs, and human IL6R monomer (1N26.pdb, aa LEU1-SER299) 196 .μs’ MD free datasets of Folding@home (foldingathome.org) from website osf.io/fs2yv/file [439]. We firstly optimized the three structures of human-ACE2-6LZG-model, human-IL6-1ALUmodel, and human-IL6-1ALU-model; from the optimized models, we get some basic structural bioinformatics such as .π -interactions, SBs, HBs, the PoissonBoltzmann electrostatic potential surfaces, the Ramachandran plot diagram, and the hydrophobic surface. Furthermore, we confirm these bioinformatics by the analysis of these open MD trajectories of [439].
13.3 New Structural Bioinformatics 13.3.1 Human ACE2 Monomer For the human-ACE2-6LZG-model (6LZG.pdb, aa SER19-ALA614, 75787 atoms) optimized, we get 7 .π -cations LYS288.NZ.+ -PHE285, LYS596.NZ.+ -PHE592, ARG357.NH2.+ -TRP48, ARG273.NH2.+ -TYR515, ARG204.NH2.+ -TRP461, ARG169.NH2.+ TRP165, and HIS493.ND1.+ -TYR497 and 24 .π -.π stackings TYR217-TRP566, TRP349TRP48-TRP349, TYR196-TYR202, TYR385-TYR381, PHE464-TYR199, TRP328-PHE327TRP328, PHE390-PHE40, TRP409-TRP477-TRP478, TRP477-TRP478, TYR497-HIS493, TRP566-TYR217, PHE504-HIS505-TYR515-PHE512, TYR255-TYR158-HIS265, TYR243TRP594, PHE588-TYR587, HIS417-PHE314-PHE315, and PHE314-HIS373. Segments TRP168-ARG169, TRP202-TRP203-ARG204, TRP459-ARG460-TRP461, ARG514-TYR515TYR516, and TYR587-PHE588 have strong SASA characters. Figure 13.1 illuminates
the Poisson-Boltzmann electrostatic potential surface (EPS), Ramachandran plot diagram, and hydrophobic surface of the optimized human-ACE2-6LZG-model, where we may see large areas of red-colored negative charges on the EPS. For the MD, we may see in Fig. 13.2 that the .α-helix in segment PRO492LEU503 unfolds into 3.10 -helix and turns during 664 .μs’ MD (Tables 13.1 and 13.2).
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Fig. 13.1 The Poisson-Boltzmann electrostatic potential surfaces, Ramachandran plot diagram, and hydrophobic surface of the optimized human-ACE2-6LZG-model
Fig. 13.2 Secondary structure of the human-ACE2-6LZG-model during 664 .μs’ MD
During the MD, the SBs GLU197-ARG204 and GLU589-LYS596 do not exist, but replaced by ASP427-LYS288, ASP427-LYS419, and GLU589ARG582, respectively; but the SBs ASP38-LYS353, ASP201-ARG219, ASP335-LYS363, ASP382-HIS401, ASP431-LYS288, ASP509-LYS187, ASP543-LYS416, ASP597-LYS600, GLU35-LYS31, GLU37-ARG393, GLU166-HIS493, GLU181-ARG177, GLU181-LYS470, GLU189-LYS112, GLU208-ARG219, GLU227-LYS458, GLU231-LYS234, GLU310-ARG306, GLU310-LYS313, GLU312-LYS309, GLU398-ARG514, GLU406-ARG518, GLU430-LYS541, GLU433-LYS288, GLU435-HIS540, GLU435-LYS541, GLU457-ARG460, GLU467-LYS465, GLU479-LYS476, and GLU549-LYS534 are strong. The SBs ASP201-ARG219, ASP597LYS600, GLU181-ARG177, GLU208-ARG219, GLU231-LYS234, GLU310-ARG306, GLU310-LYS313, GLU312-LYS309, GLU457-ARG460, GLU467-LYS465, GLU479-LYS476, and GLU549-LYS534 span several residues, respectively. We illuminate the SBs GLU435-LYS541, ASP509-LYS187, GLU166-HIS493, GLU189-LYS112, GLU406-ARG518, GLU435-HIS540, GLU37-ARG393, GLU181-LYS470, GLU227-LYS458, GLU398-ARG514, GLU430-LYS541, ASP38-LYS353, ASP382-HIS401, ASP431-LYS288, ASP543-LYS416, GLU433-LYS288, and GLU549-LYS534 spanning a large number of residues in Fig. 13.7.
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Table 13.1 All the SBs in the optimized human-ACE2-6LZG-model and in the 664 .μs’ MD Opt-SBs
664 .μs-MD-SBs
ASP111-ARG115
ASP111-ARG115, ASP111-LYS112, ASP111-LYS114, ASP111-LYS74
ASP198-ARG204
ASP136-LYS341
ASP201-ARG219
ASP198-ARG204, ASP198-LYS465
ASP206-LYS562
ASP201-ARG204, ASP201-ARG219
ASP30-HIS34
ASP206-ARG514, ASP206-LYS562
ASP335-LYS363
ASP213-LYS577
ASP355-ARG357
ASP225-HIS228
ASP382-HIS401
ASP269-ARG273
ASP38-LYS353
ASP292-LYS288, ASP292-LYS441
ASP431-LYS288
ASP295-LYS288
ASP494-LYS174
ASP303-ARG306, ASP303-LYS309
ASP499-HIS493
ASP30-HIS34
ASP509-LYS187
ASP335-LYS341, ASP335-LYS363
ASP543-LYS416
ASP350-ARG357, ASP350-ARG393, ASP350-LYS353
ASP597-LYS600
ASP355-ARG357, ASP355-LYS353
GLU166-HIS493
ASP367-HIS345, ASP367-LYS363, ASP367-LYS441
GLU181-ARG177
ASP368-LYS363
GLU181-LYS470
ASP382-ARG393, ASP382-HIS378, ASP382-HIS401, ASP382-LYS353, ASP382-LYS562
GLU189-LYS112
ASP38-LYS353
GLU197-ARG204 X
ASP427-LYS288, ASP427-LYS419
GLU208-ARG219
ASP431-LYS288, ASP431-LYS419
GLU227-LYS458
ASP471-ARG177, ASP471-LYS475
GLU22-LYS26
ASP494-ARG177, ASP494-LYS174, ASP494-LYS475
GLU231-LYS234
ASP499-ARG169, ASP499-HIS493, ASP499-LYS481
GLU310-ARG306
ASP509-ARG460, ASP509-LYS187
GLU310-LYS313
ASP543-LYS416
GLU312-LYS309
ASP597-LYS600
GLU35-LYS31
ASP609-ARG482
GLU37-ARG393
ASP67-LYS114, ASP67-LYS68
GLU398-ARG514
GLU110-LYS114, GLU110-LYS74
GLU402-ARG514
GLU140-LYS131, GLU140-LYS341, GLU140-LYS363
GLU402-ARG518
GLU145-ARG273, GLU145-HIS505, GLU145-LYS363
GLU406-ARG518
GLU150-LYS363
GLU430-LYS541
GLU166-ARG169, GLU166-HIS493
GLU433-LYS288
GLU171-LYS131
GLU435-HIS540
GLU171-LYS174
GLU435-LYS541
GLU181-ARG177, GLU181-LYS470
GLU457-ARG460
GLU182-ARG115
GLU467-LYS465
GLU189-ARG192, GLU189-LYS112
GLU479-LYS475
X GLU197-ARG219, GLU197-LYS465
GLU479-LYS476
GLU208-ARG219, GLU208-HIS195, GLU208-LYS94
GLU483-LYS476
GLU224-HIS228
GLU489-ARG482
GLU227-LYS458
GLU495-ARG177
GLU22-LYS26
GLU527-ARG582
GLU231-LYS234
GLU549-LYS534
GLU232-ARG582, GLU232-HIS228
GLU564-ARG559
GLU238-LYS234
GLU589-LYS596 X
GLU23-LYS26 GLU310-ARG306, GLU310-LYS309, GLU310-LYS313 GLU312-LYS309, GLU312-LYS313 GLU329-LYS309, GLU329-LYS353 GLU35-HIS34, GLU35-LYS31 GLU375-HIS374, GLU375-HIS378 GLU37-ARG393, GLU37-LYS353 GLU398-ARG514, GLU398-ARG518, GLU398-HIS401, GLU398-LYS562 GLU402-ARG514, GLU402-ARG518, GLU402-HIS374, GLU402-HIS378, GLU402-HIS401 GLU406-ARG518, GLU406-HIS374 GLU430-LYS288, GLU430-LYS416, GLU430-LYS419, GLU430-LYS541 GLU433-LYS247, GLU433-LYS288 GLU435-HIS540, GLU435-LYS288, GLU435-LYS416, GLU435-LYS419, GLU435-LYS541
(continued)
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Table 13.1 (continued) Opt-SBs
664 .μs-MD-SBs GLU457-ARG460 GLU467-ARG192, GLU467-LYS465 GLU479-ARG482, GLU479-LYS475, GLU479-LYS476 GLU483-ARG482 GLU489-ARG169, GLU489-ARG482, GLU489-HIS493, GLU489-LYS481 GLU495-ARG177, GLU495-HIS493, GLU495-LYS174, GLU495-LYS470, GLU495-LYS475 GLU527-ARG582 GLU536-LYS541 GLU549-LYS534, GLU549-LYS553 GLU564-ARG559, GLU564-LYS562 GLU56-LYS131 GLU571-LYS577 X GLU589-ARG582 GLU75-LYS74
Table 13.2 Some polar contacts GLU166-HIS493, GLU227-LYS458, GLU189-LYS112, GLU181-LYS470, GLU398-ARG514, GLU435-LYS541, ASP509-LYS187, GLU406ARG518, GLU37-ARG393, and GLU435-HIS540 of the human-ACE2-6LZG-model GLU166-HIS493
HIS493.NE2-GLU166.OE1 17.56%, HIS493.NE2-GLU166.OE2 20.36%, TYR497.OH-GLU166.OE1 7.39%, TYR497.OH-GLU166.OE2 4.99%
GLU227-LYS458
LYS458.NZ-GLU227.OE2 13.77%, LYS458.NZ-GLU227.OE1 9.78%, TYR454.OH-GLU227.OE2 12.18%, TYR454.OH-GLU227.OE1 9.18%
GLU189-LYS112
LYS112.NZ-GLU189.OE2 11.58%, LYS112.NZ-GLU189.OE1 10.38%
GLU181-LYS470
LYS470.NZ-GLU181.OE2 12.38%, LYS470.NZ-GLU181.OE1 9.58%
GLU398-ARG514
GLU398.N-ASP206.OD1 15.57%, GLU398.N-ASP206.OD2 15.37%, ARG514.NH1-GLU398.OE1 8.78%, ARG514.NH1-GLU398.OE2 8.58%, SER511.OG-GLU398.OE1 6.39%, SER511.OG-GLU398.OE2 6.79%
GLU435-LYS541
LYS541.NZ-GLU435.OE2 7.98%, LYS541.NZ-GLU435.OE1 6.59%, HIS540.NE2-GLU435.OE1 6.79%, HIS540.NE2-GLU435.OE2 6.59%
ASP509-LYS187
LYS187.NZ-ASP509.OD2 7.39%, LYS187.NZ-ASP509.OD1 6.99%, TYR183.OH-ASP509.OD1 17.76%, TYR183.OH-ASP509.OD2 13.57%, TRP203.NE1-ASP509.O 6.79%, TYR199.OH-ASP509.OD2 6.79%, TYR199.OH-ASP509.OD1 6.59%
GLU406-ARG518
ARG518.NE-GLU406.OE1 7.39%, ARG518.NE-GLU406.OE2 6.19%, ARG518.NH1-GLU406.OE2 5.39%, GLN522.NE2-GLU406.O 9.58%, HIS374.ND1-GLU406.OE2 8.18%, HIS374.ND1-GLU406.OE1 6.19%
GLU37-ARG393
ARG393.NH1-GLU37.OE1 7.78%, ARG393.NH2-GLU37.OE2 7.39%, ARG393.NH1-GLU37.OE2 6.99%, ARG393.NH2-GLU37.OE1 5.99%
GLU435-HIS540
HIS540.NE2-GLU435.OE1 6.79%, HIS540.NE2-GLU435.OE2 6.59%, LYS541.NZ-GLU435.OE2 7.98%, LYS541.NZ-GLU435.OE1 6.59%
The HBs with occupancy rates .≥5% during 664 .μs’ MD are listed in Tables 13.3 and 13.4. Some very interesting SBs with stronger HBs such as GLU166-HIS493, GLU227-LYS458, GLU189-LYS112, GLU181-LYS470, GLU398-ARG514, GLU435-LYS541, ASP509-LYS187, GLU406-ARG518, GLU37-ARG393, and GLU435-HIS540 are listed in
Table 13.2.
13.3.2 Human IL6 Monomer There is some early evidence that interleukin 6 (IL6) can be used as an inflammatory marker for severe COVID-19 infection with poor prognosis, in the content of the wider coronavirus pandemic. IL6 is responsible for stimulating acute phase protein synthesis. It supports the growth of B cells and is antagonistic to regulatory T cells. SBs and HBs of the optimized human-IL6-1ALU-model are listed in Tables 13.5 and 13.6. SBs GLU110-ARG113, GLU80-LYS129, GLU95-LYS120, ASP160-ARG104, ASP26-ARG30, ASP71-LYS70, ASP71-LYS86, GLU42-LYS46, and GLU51-
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13 Human ACE2, Human IL6, Human IL6R, and Human nAChRs
Fig. 13.3 Secondary structure of the human-IL6-1ALU-model during 1593 .μs’ MD
Fig. 13.4 The Poisson-Boltzmann electrostatic potential surfaces of the optimized human-IL61ALU-model
ARG40 of human-IL6-1ALU-model during 1593 .μs’ MD are illuminated in Fig. 13.8. The SB GLU110-ARG113 is with stronger HBs ARG113.NH2-GLU110.OE1 14.33%, ARG113.NH2-GLU110.OE2 12.65%, ARG113.NE-GLU110.OE2 8.39%, ARG113.NEGLU110.OE1 8.39%, and ALA114.N-GLU110.O 14.99% during the 1593 .μs’ MD.
During the 1593 .μs’ MD, we should also notice the stronger HBs between ARG182 and ASP26, ARG182.NE-ASP26.OD1 14.81%, ARG182.NE-ASP26.OD2 13.19%, ARG182.NH2-ASP26.OD1 13.07%, and ARG182.NH2-ASP26.OD2 12.77%, and the stronger HBs between SER47 and ASP160: SER47.OG-ASP160.OD2 15.95% and SER47.OGASP160.OD1 14.33%.
During the 1593 .μs’ MD, the secondary structures of the human-IL6-1ALUmodel are not variable largely (Fig. 13.3). But we should notice the PoissonBoltzmann electrostatic potential surfaces of the optimized human-IL6-1ALUmodel have large areas of positive charges (blue colored in Fig. 13.4).
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Table 13.3 The HBs (with occupancy rates .≥5%) of the human-ACE2-6LZG-model during 664 .μs’ MD VAL316.N-GLU312.O 78.24%
LYS458.N-TYR454.O 34.93%
TYR279.OH-ASN437.OD1 24.95%
SER317.N-LYS313.O 18.96%
VAL244.N-LEU240.O 76.85%
SER77.N-LEU73.O 34.73%
LEU570.N-TRP566.O 24.95%
TYR237.N-ILE233.O 18.76%
VAL487.N-LYS481.O 66.87%
ALA569.N-PRO565.O 34.53%
THR434.OG1-ASP431.OD1 24.95%
SER77.OG-LEU73.O 18.76%
VAL574.N-LEU570.O 66.27%
LEU186.N-GLU182.O 34.33%
THR118.N-LYS114.O 24.75%
ALA99.N-LEU95.O 18.56%
GLU197.N-ASP201.OD1 65.47%
THR362.OG1-LEU333.O 33.93%
SER43.N-LEU39.O 24.35%
VAL172.N-TRP168.O 18.56%
VAL93.N-ASN90.OD1 63.87%
GLU238.N-LYS234.O 33.33%
SER502.OG-CYS498.O 24.35%
MET376.N-ALA372.O 18.56%
TRP461.N-GLU457.O 62.67%
GLN76.N-PHE72.O 33.33%
ARG460.NH2-GLU457.OE2 24.35%
MET462.N-LYS458.O 18.36%
VAL488.N-LEU262.O 61.28%
HIS373.ND1-PHE369.O 33.33%
GLN531.N-GLU527.O 24.35%
LYS465.N-TRP461.O 18.16%
VAL209.N-TYR217.O 61.28%
ARG161.N-ASP157.O 33.13%
TYR252.OH-LEU156.O 24.15%
LYS309.N-GLN305.O 18.16%
GLU483.N-GLU479.O 60.48%
GLN98.N-LYS94.O 32.73%
GLN89.N-GLU22.OE1 24.15%
GLU406.N-GLU402.O 18.16%
HIS241.N-TYR237.O 59.88%
LYS481.N-TRP477.O 32.34%
ALA246.N-ALA242.O 24.15%
ARG582.N-ASN580.OD1 17.96%
LYS476.N-GLN472.O 59.68%
ILE54.N-LYS341.O 32.14%
ASN121.N-ASN117.O 23.95%
ARG518.N-ARG514.O 17.96%
SER607.N-ILE259.O 59.08%
ARG192.NE-GLU197.O 31.94%
TRP168.NE1-SER502.O 23.95%
GLN96.NE2-THR92.O 17.96%
THR449.OG1-ARG273.O 57.09%
SER124.N-LEU120.O 31.94%
TRP48.N-SER44.O 23.95%
ASN63.N-VAL59.O 17.96%
THR282.OG1-LEU278.O 54.49%
HIS374.N-LEU370.O 31.94%
ILE421.N-HIS417.O 23.75%
THR434.OG1-ASP431.OD2 17.76%
SER155.OG-ILE151.O 54.29%
ALA25.N-ILE21.O 31.74%
ILE513.N-GLU457.OE1 23.55%
THR371.N-ASP367.O 17.76%
THR517.N-ILE513.O 53.69%
TYR215.OH-GLU571.OE2 31.54%
THR52.OG1-TRP48.O 23.35%
TYR183.OH-ASP509.OD1 17.76%
SER113.OG-SER109.O 52.69%
ARG219.NE-ASP201.OD2 31.54%
GLN102.N-GLN98.O 23.35%
MET332.N-ILE358.O 17.76%
TYR521.N-THR517.O 51.70%
ASN51.ND2-SER47.O 31.34%
GLU310.N-ARG306.O 23.15%
ASP299.N-ASP295.O 17.56%
THR229.OG1-ASP225.O 51.30%
TRP566.NE1-TYR207.O 31.34%
LEU370.N-MET366.O 23.15%
GLU312.N-PHE308.O 17.56%
SER47.OG-SER43.O 51.30%
TYR215.OH-GLU571.OE1 31.34%
THR453.N-THR449.O 22.95%
GLN96.N-THR92.O 17.56%
VAL132.N-LEU142.O 51.10%
ILE436.N-ASN432.O 30.94%
ASN117.N-SER113.O 22.95%
GLU435.N-ASP431.O 17.56%
VAL226.N-LEU222.O 50.70%
LYS187.N-TYR183.O 30.74%
TYR217.OH-ASP225.OD2 22.95%
HIS493.NE2-GLU166.OE1 17.56%
LEU95.N-LEU91.O 50.50%
HIS535.N-CYS530.O 30.74%
GLU457.N-THR453.O 22.95%
ARG460.NH2-GLU457.OE1 17.37%
THR453.OG1-THR449.O 49.90%
VAL447.N-ALA443.O 30.74%
GLN442.N-PHE438.O 22.95%
ASN149.N-LEU144.O 17.17%
MET123.N-ILE119.O 49.50%
THR496.OG1-ASP494.OD1 30.74%
ILE358.N-SER331.OG 22.75%
LEU554.N-ALA550.O 17.17%
GLU375.N-THR371.O 48.90%
LEU97.N-VAL93.O 30.74%
GLN300.N-ALA296.O 22.75%
SER47.N-SER43.O 17.17%
HIS378.N-HIS374.O 48.30%
THR78.OG1-LYS74.O 30.34%
GLN221.N-SER218.O 22.75%
ARG245.NH2-GLY260.O 17.17%
THR567.OG1-TYR215.O 47.90%
ILE446.N-GLN442.O 29.74%
ALA80.N-GLN76.O 22.75%
ARG357.N-TRP349.O 16.97%
VAL283.N-TYR279.O 47.70%
SER545.OG-ASP543.OD2 29.74%
MET62.N-ASN58.O 22.55%
ARG219.NH2-GLU208.OE1 16.97%
THR517.OG1-ILE513.O 47.31%
PHE40.N-ALA36.O 29.54%
TRP302.NE1-GLN300.OE1 22.36%
TYR454.N-LEU450.O 16.97%
ALA36.N-PHE32.O 46.91%
LEU439.N-GLU435.O 29.34%
ARG161.NH1-SER155.O 22.36%
MET360.N-MET332.O 16.77%
LEU148.N-LEU143.O 46.71%
LYS74.N-SER70.O 29.14%
THR445.OG1-LYS441.O 22.36%
GLN380.NE2-MET376.O 16.77%
THR129.OG1-THR125.O 45.71%
LEU116.N-LYS112.O 28.74%
GLU231.N-GLU227.O 22.36%
TRP459.N-MET455.O 16.77%
VAL506.N-LEU503.O 45.51%
THR496.OG1-ASP494.OD2 28.54%
SER502.OG-ASP499.O 22.16%
ASN49.N-LEU45.O 16.77%
MET480.N-LYS476.O 45.51%
TRP163.N-ASN159.O 28.54%
LYS114.N-GLU110.O 22.16%
LYS596.N-PHE592.O 16.57%
SER411.OG-ILE407.O 43.51%
LEU73.N-TRP69.O 28.34%
GLN42.N-ASP38.O 22.16%
ASN586.N-ARG582.O 16.37%
SER218.N-GLN221.OE1 43.51%
GLN89.N-GLU22.OE2 28.14%
ASP67.N-ASN63.O 21.96%
LEU558.N-LEU554.O 16.37%
ARG245.N-HIS241.O 43.31%
LEU359.N-THR347.O 28.14%
LYS26.N-GLU22.O 21.96%
ARG219.NH1-ASP201.OD1 16.37%
VAL298.N-THR294.O 42.32%
LEU29.N-ALA25.O 27.94%
ASP225.N-GLN221.O 21.76%
LEU391.N-ASN33.OD1 16.37%
TYR183.N-LEU179.O 42.12%
LEU120.N-LEU116.O 27.94%
TYR217.N-VAL209.O 21.76%
LEU45.N-TYR41.O 16.37%
LEU440.N-ILE436.O 41.92%
LEU320.N-PHE315.O 27.94%
ALA153.N-ASN149.O 21.56%
LEU278.N-TRP275.O 16.37%
TRP477.NE1-ASP499.OD2 41.92%
ARG169.NH1-MET270.O 27.74%
ALA65.N-ASN61.O 21.56%
GLU479.N-LYS475.O 16.17%
THR122.OG1-THR118.O 41.72%
SER167.OG-TRP163.O 27.74%
ASN572.N-LEU568.O 21.56%
TYR243.OH-THR282.O 16.17%
SER128.OG-SER124.O 41.72%
ARG115.N-ASP111.O 27.54%
ARG460.NH2-TYR510.O 21.36%
PHE28.N-GLN24.O 16.17%
TYR237.OH-VAL485.O 41.52%
VAL59.N-THR55.O 27.54%
MET249.N-ARG245.O 21.16%
GLN522.N-ARG518.O 16.17%
ALA372.N-ASP368.O 41.32%
LEU456.N-PHE452.O 27.54%
ILE513.N-GLU457.OE2 21.16%
SER170.OG-GLU166.O 16.17%
PHE464.N-ARG460.O 41.12%
ASN51.N-SER47.O 27.35%
TRP302.N-MET297.O 20.96%
LEU418.N-THR414.O 15.97%
VAL343.N-ASN51.O 40.92%
ILE151.N-GLY147.O 27.35%
GLN524.NE2-ASN578.O 20.96%
GLU402.N-GLU398.O 15.77%
THR27.OG1-GLU23.O 40.72%
SER113.N-SER109.O 27.35%
ASN58.ND2-ASN53.O 20.76%
ARG482.N-TRP478.O 15.77%
ILE119.N-ARG115.O 40.52%
ASN599.N-LEU595.O 27.15%
ARG161.NH2-LEU267.O 20.76%
LEU450.N-ILE446.O 15.77%
THR593.OG1-GLU589.O 40.12%
THR371.OG1-ASP367.O 27.15%
GLN526.N-GLN522.O 20.56%
SER317.OG-LYS313.O 15.77%
THR125.OG1-ASN121.O 39.72%
ALA71.N-ASP67.O 27.15%
LYS94.N-ASN90.O 20.56%
ARG219.NH2-GLU208.OE2 15.57%
LEU444.N-LEU440.O 39.72%
SER44.N-PHE40.O 27.15%
HIS493.NE2-GLU166.OE2 20.36%
GLU398.N-ASP206.OD1 15.57%
TYR516.OH-THR229.OG1 39.52%
ILE126.N-THR122.O 26.95%
ALA46.N-GLN42.O 20.36%
GLN472.N-PRO469.O 15.57%
LEU262.N-GLY486.O 39.32%
THR414.OG1-SER411.O 26.95%
MET455.N-PRO451.O 20.16%
LYS476.NZ-GLU479.OE1 15.57%
LEU595.N-LEU591.O 39.12%
ALA242.N-GLU238.O 26.75%
GLU75.N-ALA71.O 20.16%
ARG192.N-ASN188.O 15.37%
GLN101.NE2-ALA80.O 38.92%
ASN64.N-GLN60.O 26.75%
GLU467.N-MET462.O 20.16%
LYS313.NZ-GLU310.OE2 15.37%
VAL184.N-TYR180.O 38.72%
PHE592.N-PHE588.O 26.75%
THR593.N-GLU589.O 19.96%
GLN175.N-GLU171.O 15.37%
PHE525.N-TYR521.O 37.92%
SER545.OG-ASP543.OD1 26.55%
GLN60.N-GLU56.O 19.96%
GLU329.N-GLN325.O 15.37%
ILE484.N-MET480.O 37.52%
HIS401.N-ASN397.O 26.55%
PHE315.N-ALA311.O 19.96%
LYS313.NZ-GLU310.OE1 15.37%
TYR180.N-LEU176.O 37.13%
TYR217.OH-ASP225.OD1 26.35%
ASP382.N-HIS378.O 19.76%
GLU398.N-ASP206.OD2 15.37%
ALA443.N-LEU439.O 36.73%
GLU181.N-ARG177.O 26.15%
LEU410.N-GLU406.O 19.76%
ALA164.N-GLU160.O 15.17%
(continued)
430
13 Human ACE2, Human IL6, Human IL6R, and Human nAChRs
Table 13.3 (continued) ILE379.N-GLU375.O 36.53%
HIS241.NE2-GLY486.O 26.15%
SER411.N-ILE407.O 19.56%
SER331.OG-PHE327.O 36.53%
THR229.N-ASP225.O 26.15%
LYS247.N-TYR243.O 19.36%
VAL318.N-PHE314.O 36.53%
MET152.N-LEU148.O 25.95%
PHE400.N-ASN397.OD1 15.17%
VAL463.N-TRP459.O 19.36%
CYS530.N-GLN526.O 36.13%
SER420.N-LYS416.O 25.95%
LEU424.N-LEU418.O 19.16%
GLU166.N-LEU162.O 35.93%
ASN33.N-LEU29.O 25.75%
ARG115.NH1-GLU182.OE2 19.16%
SER70.N-GLY66.O 35.13%
TYR252.N-LEU248.O 25.75%
ARG115.NH1-GLU182.OE1 19.16%
TRP349.N-ARG357.O 25.35%
Table 13.4 The HBs (with occupancy rates .≥5%) of the human-ACE2-6LZG-model during 664 .μs’ MD (continuation) LEU248.N-VAL244.O 14.97%
TYR587.N-PRO583.O 10.98%
ARG393.NE-GLN388.O 7.98%
GLY260.N-SER257.O 6.39%
THR519.OG1-TYR515.O 14.97%
ALA386.N-ASP382.O 10.98%
TYR207.OH-THR517.OG1 7.98%
SER511.OG-GLU398.OE1 6.39%
VAL185.N-GLU181.O 14.97%
SER44.OG-PHE40.O 10.98%
VAL364.N-ASP368.OD2 7.98%
HIS493.ND1-GLU489.OE1 6.39%
SER70.OG-GLY66.O 14.97%
SER128.N-SER124.O 10.78%
PHE72.N-LYS68.O 7.98%
THR20.OG1-GLU23.OE1 6.39%
LYS476.NZ-GLU479.OE2 14.97%
GLN598.N-TRP594.O 10.78%
THR347.OG1-PRO346.O 7.98%
VAL212.N-ASP216.OD1 6.19%
ARG460.N-LEU456.O 14.97%
SER170.N-GLU166.O 10.78%
LYS541.NZ-GLU435.OE2 7.98%
HIS401.NE2-HIS378.O 6.19%
HIS228.N-GLU224.O 14.77%
SER545.N-ASP543.OD1 10.78%
ARG161.NE-HIS265.O 7.98%
GLU227.N-ILE223.O 6.19%
GLU160.N-ASP157.OD2 14.57%
GLN340.NE2-THR52.O 10.78%
SER155.OG-GLU160.OE1 7.78%
ARG518.NE-GLU406.OE2 6.19%
ALA412.N-MET408.O 14.57%
THR347.N-LEU359.O 10.78%
ARG393.NH1-GLU37.OE1 7.78%
LYS441.NZ-ILE291.O 6.19%
ARG204.N-GLY200.O 14.57%
VAL107.N-GLY104.O 10.58%
LEU162.N-TYR158.O 7.78%
HIS374.ND1-GLU406.OE1 6.19%
ALA191.N-LYS187.O 14.57%
HIS378.ND1-GLU375.OE2 10.58%
ASP201.N-ASP198.OD2 7.78%
GLN552.NE2-THR548.O 6.19%
TYR202.N-ASP198.O 14.37%
ARG245.NH2-GLY605.O 10.58%
THR118.OG1-LYS114.O 7.58%
ARG393.NH2-GLU37.OE1 5.99%
ARG115.NE-GLU182.OE2 14.37%
ARG482.NH1-THR608.O 10.58%
GLU433.N-ASP431.OD1 7.58%
SER155.OG-GLU160.OE2 5.99%
ALA533.N-LEU529.O 14.37%
HIS34.N-ASP30.O 10.38%
SER331.N-PHE327.O 7.58%
TYR196.OH-GLN102.OE1 5.99%
ALA193.N-GLU189.O 14.37%
SER124.OG-LEU120.O 10.38%
ARG518.NE-GLU406.OE1 7.39%
ILE259.N-SER257.OG 5.99%
GLN60.NE2-GLU56.O 14.37%
GLN81.NE2-SER77.O 10.38%
ASN137.N-ASN134.OD1 7.39%
ARG177.NE-GLU181.OE2 5.79%
GLU37.N-ASN33.O 14.37%
MET82.N-LEU79.O 10.38%
ASP295.N-ASP292.OD2 7.39%
LEU392.N-PRO389.O 5.79% ARG357.NE-ASP355.OD2 5.79%
ARG115.NE-GLU182.OE1 14.17%
LYS112.NZ-GLU189.OE1 10.38%
TYR497.OH-GLU166.OE1 7.39%
GLN552.N-THR548.O 14.17%
THR414.OG1-CYS542.O 10.38%
LYS187.NZ-ASP509.OD2 7.39%
LYS234.NZ-GLU231.OE2 5.79%
PHE32.N-PHE28.O 14.17%
THR496.N-ASP494.OD2 10.18%
ASN194.ND2-MET190.O 7.39%
LYS600.NZ-ASP597.OD2 5.79%
GLN380.NE2-PRO321.O 14.17%
GLN388.N-TYR385.O 10.18%
ARG393.NH2-GLU37.OE2 7.39%
PHE588.N-LEU584.O 5.79%
TRP478.N-MET474.O 13.97%
TYR199.N-ASN188.OD1 10.18%
LYS553.N-GLU549.O 7.39%
ALA403.N-GLY399.O 5.79%
ASN188.N-VAL184.O 13.97%
THR365.OG1-ASP368.OD1 10.18%
ASN154.ND2-GLU150.O 7.39%
PHE512.N-GLU457.OE2 5.79%
THR362.N-LEU333.O 13.97%
SER167.N-TRP163.O 10.18%
GLN175.NE2-GLU171.O 7.19%
ALA403.N-PHE400.O 5.79%
LYS458.NZ-GLU227.OE2 13.77%
LYS68.N-ASN64.O 9.98%
ARG357.NH1-ASP355.OD1 7.19%
SER547.OG-GLU549.OE2 5.59%
HIS535.NE2-PRO538.O 13.77%
VAL404.N-PHE400.O 9.98%
THR129.N-THR125.O 7.19%
SER511.OG-GLU457.OE2 5.59%
GLU160.N-ASP157.OD1 13.77%
TYR587.OH-GLN442.OE1 9.98%
ARG169.NH2-TRP165.O 7.19%
ASN33.ND2-LEU29.O 5.59%
ARG161.NH2-ASN277.OD1 13.77%
SER43.OG-LEU39.O 9.98%
ARG357.NH1-ASP355.OD2 7.19%
GLN531.NE2-GLU527.O 5.59%
GLU527.N-PHE523.O 13.57%
ILE407.N-ALA403.O 9.98%
VAL364.N-ASP368.OD1 7.19%
SER507.OG-ALA501.O 5.39%
TYR183.OH-ASP509.OD2 13.57%
PHE369.N-THR365.O 9.98%
ASN330.N-GLY326.O 7.19%
SER155.N-MET152.O 5.39%
SER563.OG-GLU564.OE1 13.57%
LYS458.NZ-GLU227.OE1 9.78%
ARG393.N-PRO389.O 7.19%
THR362.N-THR334.O 5.39%
VAL573.N-ALA569.O 13.57%
ALA311.N-ILE307.O 9.78%
LEU266.N-PRO263.O 7.19%
SER409.OG-GLU406.OE1 5.39%
LEU240.N-LEU236.O 13.17%
SER545.N-ASP543.OD2 9.78%
THR129.OG1-ILE126.O 7.19%
TYR497.N-ASP494.O 5.39%
GLU571.N-THR567.O 13.17%
LYS577.NZ-GLY214.O 9.58%
GLY66.N-MET62.O 7.19%
SER602.N-ASN599.O 5.39%
LYS419.NZ-PHE428.O 12.97%
LEU100.N-GLN96.O 9.58%
GLN139.NE2-ASN137.OD1 7.19%
ARG518.NH1-GLU406.OE2 5.39%
LEU39.N-GLU35.O 12.97%
HIS378.ND1-GLU375.OE1 9.58%
LEU560.N-MET557.O 6.99%
GLU589.N-ASN586.O 5.39%
GLU35.N-LYS31.O 12.97%
GLN522.NE2-GLU406.O 9.58%
LYS475.NZ-ASP471.OD2 6.99%
THR294.N-ASP292.OD2 5.19%
MET190.N-LEU186.O 12.77%
ASP30.N-LYS26.O 9.58%
ARG393.NH1-GLU37.OE2 6.99%
ASN194.ND2-GLN102.O 5.19%
ASP136.N-ASN134.OD1 12.77%
CYS542.N-LEU539.O 9.58%
GLU182.N-PRO178.O 6.99%
ARG306.NE-GLU310.OE2 5.19%
THR496.N-ASP494.OD1 12.77%
LYS470.NZ-GLU181.OE1 9.58%
LYS187.NZ-ASP509.OD1 6.99%
ARG357.NE-ASP355.OD1 5.19%
LYS419.N-PRO415.O 12.77%
LEU529.N-PHE525.O 9.58%
SER611.OG-ALA614.OXT 6.99%
ILE307.N-ASP303.O 5.19%
GLN101.N-LEU97.O 12.77%
ASN61.N-GLU57.O 9.38%
ALA528.N-GLN524.O 6.99%
ASN437.ND2-GLU433.O 4.99%
GLN305.N-ASP303.OD1 12.57%
ASN397.ND2-ASP206.O 9.38%
GLN300.NE2-LEU423.O 6.99%
ASN154.N-GLU150.O 4.99%
SER563.OG-GLU564.OE2 12.57%
LEU79.N-GLU75.O 9.38%
THR294.OG1-ASP292.OD1 6.79%
THR434.N-ASP431.OD2 4.99%
LYS470.NZ-GLU181.OE2 12.38%
MET383.N-ILE379.O 9.18%
TRP203.NE1-ASP509.O 6.79%
LYS600.NZ-ASP597.OD1 4.99%
TYR127.N-MET123.O 12.38%
TYR454.OH-GLU227.OE1 9.18%
TYR279.N-THR276.O 6.79%
TYR497.OH-GLU166.OE2 4.99%
TYR454.OH-GLU227.OE2 12.18%
THR434.OG1-GLN429.O 9.18%
ASN578.ND2-ASP225.OD1 6.79%
THR125.N-ASN121.O 4.99%
PHE555.N-GLY551.O 12.18%
THR347.OG1-HIS345.O 8.98%
ARG273.N-ASP269.OD1 6.79%
GLU22.N-SER19.O 4.99%
ASN90.N-GLU22.OE2 12.18%
THR52.N-TRP48.O 8.98%
ARG219.N-GLU208.OE1 6.79%
ARG177.NE-GLU181.OE1 4.99%
SER511.OG-GLU457.OE1 12.18%
GLU433.N-ASP431.OD2 8.98%
TYR279.OH-ASN437.O 6.79%
LYS309.NZ-GLU312.OE2 4.99%
ASN90.N-GLU22.OE1 12.18%
LYS481.NZ-ASP499.OD2 8.98%
SER44.OG-ASP350.O 6.79%
ALA532.N-ALA528.O 4.99%
TRP459.NE1-TRP473.O 11.98%
ASN149.ND2-ASP269.OD1 8.98%
LYS541.N-PRO538.O 6.79%
THR20.OG1-GLU23.OE2 4.99%
LYS313.N-LYS309.O 11.98%
LYS441.N-ASN437.O 8.78%
ARG559.N-PHE555.O 6.79%
LEU503.N-PRO500.O 4.99%
(continued)
13.3 New Structural Bioinformatics
431
Table 13.4 (continued) GLN305.N-ASP303.OD2 11.98%
TYR381.OH-LEU560.O 8.78%
SER511.OG-GLU398.OE2 6.79%
GLN524.N-LEU520.O 11.78%
VAL212.N-ASP216.OD2 8.78%
HIS540.NE2-GLU435.OE1 6.79%
MET366.N-THR294.OG1 11.78%
HIS195.N-ALA191.O 8.78%
TRP271.NE1-SER502.O 4.99%
TYR199.OH-ASP509.OD2 6.79%
LEU351.N-ASP355.O 11.58%
TRP165.N-ARG161.O 8.78%
MET270.N-ASN149.OD1 6.59%
LYS112.NZ-GLU189.OE2 11.58%
TRP477.NE1-ASP499.OD1 8.78%
LYS541.NZ-GLU435.OE1 6.59%
MET557.N-LYS553.O 11.58%
GLY130.N-ILE126.O 8.78%
HIS540.NE2-GLU435.OE2 6.59%
GLU189.N-VAL185.O 11.58%
LEU142.N-VAL132.O 8.78%
TYR199.OH-ASP509.OD1 6.59%
GLN300.NE2-GLY422.O 11.38%
ARG514.NH1-GLU398.OE1 8.78%
SER563.OG-GLN388.OE1 6.59%
ASN556.N-GLN552.O 11.38%
THR27.N-GLU23.O 8.58%
ARG219.N-GLU208.OE2 6.59%
GLN24.N-THR20.O 11.38%
GLN526.NE2-SER411.OG 8.58%
HIS493.ND1-GLU489.OE2 6.59%
ASN149.ND2-ASP269.OD2 11.38%
MET297.N-VAL293.O 8.58%
GLU208.N-GLY205.O 6.59%
TYR243.N-HIS239.O 11.38%
TYR385.N-TYR381.O 8.58%
HIS239.N-PRO235.O 6.59%
ARG169.NE-ASP499.OD1 11.38%
LYS465.NZ-GLU467.OE2 8.58%
LYS465.NZ-GLU467.OE1 6.59%
ASN599.ND2-HIS239.ND1 11.18%
ASN188.ND2-PHE464.O 8.58%
PHE512.N-GLU457.OE1 6.39%
THR365.OG1-ASP368.OD2 11.18%
ARG514.NH1-GLU398.OE2 8.58%
GLU564.N-GLY561.O 6.39%
THR282.N-LEU278.O 11.18%
GLN81.NE2-GLN101.O 8.58%
ASP295.N-ASP292.OD1 6.39%
LYS31.N-THR27.O 11.18%
ARG273.N-ASP269.OD2 8.38%
ASN546.ND2-ALA533.O 6.39%
v SER547.N-ILE544.O 11.18%
ASP355.N-GLY352.O 8.38%
ARG460.NH1-VAL506.O 6.39%
THR122.N-THR118.O 11.18%
SER77.OG-LEU100.O 8.38%
PHE523.N-THR519.O 6.39%
TYR127.OH-SER502.O 11.18%
ASN437.N-GLU433.O 8.38%
THR276.OG1-THR445.OG1 6.39%
THR294.OG1-ASP292.OD2 8.38%
ASN580.N-GLN524.OE1 6.39%
HIS374.ND1-GLU406.OE2 8.18%
THR519.N-TYR515.O 6.39%
THR449.OG1-THR445.O 8.18%
TYR50.N-ALA46.O 6.39%
PHE390.N-ASN33.OD1 8.18%
LYS234.NZ-GLU231.OE1 6.39%
Table 13.5 All the SBs in the optimized human-IL6-1ALU-model and in the 1593 .μs’ MD Opt-SBs
1593 .μs-MD-SBs
ASP160-ARG104
ASP134-LYS120, ASP134-LYS128, ASP134-LYS131, ASP134-LYS86
ASP26-ARG30
ASP160-ARG104, ASP160-ARG40, ASP160-HIS164, ASP160-LYS46, ASP160-LYS54
ASP71-LYS70, ASP71-LYS86
ASP26-ARG182, ASP26-ARG24, ASP26-ARG30, ASP26-LYS27
GLU110-ARG113
ASP34-ARG30
GLU172-LYS171
ASP71-LYS66, ASP71-LYS70, ASP71-LYS86
GLU42-LYS46
GLU106-ARG104, GLU106-LYS46
GLU51-ARG40
GLU109-ARG113
GLU80-LYS129
GLU110-ARG113, GLU110-LYS41
GLU95-LYS120
GLU172-ARG168, GLU172-ARG179, GLU172-LYS171, GLU172-LYS54, GLU172-LYS66, GLU172-LYS70 GLU23-ARG182, GLU23-ARG24, GLU23-ARG30, GLU23-LYS128, GLU23-LYS129, GLU23-LYS27 GLU42-LYS41, GLU42-LYS46 GLU51-ARG168, GLU51-ARG40, GLU51-HIS164, GLU51-LYS171, GLU51-LYS54 GLU55-ARG168, GLU55-ARG179, GLU55-ARG40, GLU55-HIS164, GLU55-LYS171, GLU55-LYS54, GLU55-LYS66 GLU59-ARG168, GLU59-ARG40, GLU59-HIS164, GLU59-LYS150, GLU59-LYS54, GLU59-LYS66 GLU69-ARG179, GLU69-ARG182, GLU69-LYS66, GLU69-LYS70, GLU69-LYS86 GLU80-ARG182, GLU80-LYS128, GLU80-LYS129, GLU80-LYS131, GLU80-LYS70 GLU81-LYS128, GLU81-LYS129, GLU81-LYS131 GLU93-LYS150, GLU93-LYS66, GLU93-LYS70 GLU95-LYS120 GLU99-ARG113, GLU99-LYS120
13.3.3 Human IL6R Monomer IL6R is the IL6 receptor which has been shown to interact with IL6 and ciliary neurotrophic factor. The IL6 receptor is a protein complex consisting of an IL6 receptor subunit (IL6R) and interleukin 6 signal transducer glycoprotein 130. Few .π-interactions ARG274.NH2.+ -TRP284, ARG237.NH2.+ -TRP287, LYS105.NZ.+ -PHE103, TRP214-HIS261-TRP214, TRP219-PHE234-TRP219, and PHE155-TYR148 are in the human-IL6R-1N26-model optimized. The optimized human-IL6R-1N26-model has six .β-sheets and one helix (listed in Table 13.7 and illuminated in Fig. 13.5 during the 196 .μs’ MD). The Poisson-Boltzmann
432
13 Human ACE2, Human IL6, Human IL6R, and Human nAChRs
Fig. 13.5 Secondary structure of the human-IL6R-1N26-model during 196 .μs’ MD
Fig. 13.6 The Poisson-Boltzmann electrostatic potential surfaces of the optimized human-IL6R1N26-model
electrostatic potential surfaces of the optimized human-IL6R-1N26-model shows us there are large blue-colored positive charges (Fig. 13.6). As all the SBs and HBs in the humanACE2-6LZG-model and humanIL61ALU-model (Figs. 13.7 and 13.8), all the SBs and HBs in the optimized human-IL6R-1N26-model and in the 196 .μs’ MD are listed in Tables 13.8 and 13.9. SBs ASP35-ARG79, ASP198-LYS105, GLU114-LYS154, GLU235ARG274, GLU241-ARG268, GLU290-ARG239, ASP71-LYS45, ASP141-ARG4, and ASP221-HIS256 are illuminated in Fig. 13.9.
13.3.4 Human α4β2-, α7-, and αβγ δ-nAChR It is reported in [252] that the Y674-R685 (YQTQTNSPRRAR) peptide of SARSCoV-2 spike exhibits favorable binding affinity to nicotinic acetylcholine receptors (nAChRs). In [252], there is a possible binding of the Y674-R685 region to three
13.3 New Structural Bioinformatics
433
Table 13.6 The HBs (with occupancy rates .≥5%) of the human-IL6-1ALU-model during 1593 .μs’ MD Opt-HBs
1593 .μs-MD-HBs
ALA130.N-LEU126.O
VAL121.N-MET117.O 64.27%
ALA114.N-GLU110.O 14.99%
ALA145.N-PRO141.O
VAL115.N-GLN111.O 64.21%
LYS27.N-GLU23.O 14.93%
ALA58.N-GLU59.OE1
THR163.OG1-GLN159.O 60.79%
ARG182.NE-ASP26.OD1 14.81%
ALA68.N-ASP71.OD2
SER118.N-ALA114.O 55.22%
LYS171.N-LEU167.O 14.57%
ARG113.N-GLU109.O
VAL85.N-GLU81.O 51.86%
GLN102.N-LEU98.O 14.51%
ARG113.NH1-GLU110.OE2
ILE29.N-ILE25.O 47.12%
LYS41.N-SER37.O 14.45%
ARG168.NH2-GLU51.O
ILE123.N-THR119.O 46.82%
THR142.OG1-ASP140.OD1 14.45%
ARG168.NH2-SER53.O
ILE166.N-THR162.O 44.84%
GLN116.NE2-GLU99.OE1 14.45%
ARG182.NH2-ARG179.O
SER176.N-GLU172.O 43.94%
SER47.OG-ASP160.OD1 14.33%
ARG24.NH2-SER21.OG
SER177.OG-PHE173.O 42.93%
ARG113.NH2-GLU110.OE1 14.33%
ARG30.NE-ASP26.OD1
LEU181.N-SER177.O 42.51%
ASN144.N-ASP140.O 14.33%
ARG30.NH2-ASP26.OD2
SER169.N-LEU165.O 41.61%
LEU147.N-THR143.O 14.27%
ARG40.N-ILE36.O
ILE36.N-ILE32.O 39.69%
ALA130.N-LEU126.O 13.79%
ARG40.NH1-GLU51.OE2
THR119.OG1-VAL115.O 39.21%
LYS150.N-SER146.O 13.55%
ARG40.NH2-GLU51.OE1
LEU33.N-ILE29.O 36.03%
ARG179.N-GLN175.O 13.43%
ASN103.ND2-GLU99.O
GLN127.N-ILE123.O 35.37%
THR137.OG1-LEU133.O 13.25%
ASN61.N-ALA58.O
SER37.OG-LEU33.O 33.99%
ARG182.NE-ASP26.OD2 13.19%
ASN79.ND2-GLU81.OE2
GLN175.N-LYS171.O 33.57%
ARG182.NH2-ASP26.OD1 13.07%
ASP160.N-GLN156.O
PHE170.N-ILE166.O 33.45%
HIS164.N-ASP160.O 12.95%
ASP26.N-SER22.O
THR43.OG1-LEU39.O 33.45%
ARG182.NH2-ASP26.OD2 12.77%
ASP26.OD2-ARG30.NH2
GLU172.N-ARG168.O 32.85%
ARG113.NH2-GLU110.OE2 12.65%
ASP34.N-ARG30.O
SER176.OG-GLU172.O 31.95%
LYS86.N-THR82.O 12.59%
CYS44.N-ARG40.O
LEU174.N-PHE170.O 30.76%
TYR100.OH-GLN159.OE1 12.59%
GLN102.NE2-GLU109.OE2
LEU84.N-GLU80.O 29.80%
CYS83.N-ASN79.O 12.53%
GLN116.N-ALA112.O
THR162.OG1-LEU158.O 29.26%
SER177.N-PHE173.O 12.29%
GLN127.N-ILE123.O
CYS44.N-ARG40.O 29.02%
LEU158.N-ASN155.OD1 12.29%
GLN175.N-LYS171.O
THR89.N-VAL85.O 28.30%
ARG30.N-ASP26.O 11.99%
GLU110.OE2-ARG113.NH1
ALA112.N-SER108.O 27.34%
ALA153.N-THR149.O 11.81%
GLU172.OE2-LYS171.NZ
ARG113.N-GLU109.O 27.28%
GLN116.NE2-GLU99.OE2 11.75%
GLU42.OE2-LYS46.NZ
LEU167.N-THR163.O 27.16%
SER108.N-GLU42.OE2 11.21%
GLU51.OE1-ARG40.NH2
ILE88.N-LEU84.O 26.62%
TYR100.N-VAL96.O 11.15%
GLU51.OE2-ARG40.NH1
MET117.N-ARG113.O 25.72%
ARG182.N-LEU178.O 10.85%
GLU55.N-GLU55.OE2
THR149.OG1-ALA145.O 25.06%
GLU106.N-GLU42.OE2 10.67%
GLU59.N-GLU59.OE1
LEU92.N-ILE88.O 23.98%
LEU165.N-MET161.O 10.37%
GLU93.N-THR89.O
THR162.OG1-GLN154.OE1 23.98%
SER47.OG-THR43.O 10.01%
GLU99.N-GLU95.O
ASN79.N-GLY72.O 23.68%
ASN103.N-GLU99.O 9.83%
GLY72.N-GLU69.O
GLN116.N-ALA112.O 23.68%
LYS46.N-GLU42.O 9.83%
GLY90.N-LYS86.O
GLN159.N-ASN155.O 23.44%
MET161.N-TRP157.O 9.77%
HIS164.N-ASP160.O
LEU91.N-ILE87.O 23.08%
SER108.N-GLU42.OE1 9.65%
ILE123.N-THR119.O
SER108.OG-GLU42.OE2 22.60%
GLU106.N-GLU42.OE1 9.47%
ILE36.N-ILE32.O
SER108.OG-GLU42.OE1 22.54%
LEU39.N-GLY35.O 9.35%
LEU122.N-SER118.O
ASP26.N-SER22.O 22.36%
GLN159.NE2-LEU151.O 9.29%
LEU126.N-LEU122.O
ARG168.N-HIS164.O 21.88%
SER107.N-GLU42.OE2 9.23%
LEU148.N-ASN144.O
GLN124.N-LYS120.O 21.64%
GLN183.N-ALA180.O 8.99%
LEU174.N-PHE170.O
SER169.OG-LEU165.O 21.22%
THR20.OG1-GLU23.OE2 8.87%
LEU178.N-LEU174.O
THR162.N-LEU158.O 21.10%
GLN102.NE2-LEU98.O 8.81%
LEU181.N-SER177.O
GLN152.N-LEU148.O 20.92%
SER118.OG-ALA114.O 8.75%
LEU57.N-LYS54.O
GLU42.N-ALA38.O 20.68%
SER53.OG-GLU51.OE2 8.75%
LEU84.N-GLU80.O
LEU178.N-LEU174.O 20.50%
THR20.N-GLU23.OE2 8.69%
LYS120.NZ-GLU95.OE1
ALA145.N-PRO141.O 20.38%
PHE94.N-GLY90.O 8.57%
LYS129.N-LEU126.O
GLU99.N-GLU95.O 20.08%
ARG113.NE-GLU110.OE2 8.39%
LYS129.NZ-MET184.OXT
ASP34.N-ARG30.O 19.96%
ARG113.NE-GLU110.OE1 8.39%
LYS129.NZ-GLU80.OE1
GLN159.NE2-GLN154.O 19.78%
LEU19.N-GLU23.OE2 8.39%
LYS171.NZ-GLU172.OE2
THR143.OG1-ASP140.OD2 19.72%
SER107.N-GLU42.OE1 8.27%
LYS27.N-GLU23.O
SER146.N-THR142.O 19.42%
THR143.N-ASP140.OD2 8.03%
LYS46.N-THR43.O
LYS120.N-GLN116.O 19.36%
MET184.N-LEU181.O 8.03%
LYS46.NZ-GLU42.OE2
ALA180.N-SER176.O 19.18%
LEU122.N-SER118.O 8.03%
LYS70.NZ-ASP71.OD1
GLN28.NE2-SER118.O 19.06%
ASP71.N-ALA68.O 7.97%
LYS86.N-THR82.O
THR149.N-ALA145.O 19.00%
SER52.N-ASN48.O 7.79%
LYS86.NZ-LYS66.O
THR163.N-GLN159.O 18.82%
ALA68.N-ASP71.OD1 7.61%
LYS86.NZ-ASP71.OD2
THR143.OG1-ASP140.OD1 18.65%
THR143.N-ASP140.OD1 7.55%
PHE105.N-LEU101.O
PHE173.N-SER169.O 18.29%
ASP160.N-GLN156.O 7.49%
(continued)
434
13 Human ACE2, Human IL6, Human IL6R, and Human nAChRs
Table 13.6 (continued) Opt-HBs
1593 .μs-MD-HBs
PHE170.N-ILE166.O
LEU151.N-LEU147.O 18.17%
LEU19.N-GLU23.OE1 7.49%
PHE173.N-SER169.O
LEU148.N-ASN144.O 17.93%
THR20.OG1-GLU23.OE1 7.25%
SER108.OG-GLU42.OE1
SER146.OG-THR142.O 17.93%
SER53.OG-MET49.O 7.13%
SER118.OG-ALA114.O
THR82.N-ASN79.OD1 17.69%
ALA38.N-ASP34.O 7.13%
SER146.OG-THR142.O
PHE105.N-LEU101.O 17.45%
SER53.OG-GLU51.OE1 7.07%
SER169.N-LEU165.O
THR43.N-LEU39.O 17.03%
SER37.N-LEU33.O 7.01%
SER176.OG-GLU172.O
GLN102.NE2-GLN116.OE1 16.67%
LEU98.N-PHE94.O 6.83%
SER177.N-PHE173.O
ILE25.N-SER21.O 16.37%
THR20.N-GLU23.OE1 6.77%
SER177.OG-PHE173.O
THR142.OG1-ASP140.OD2 15.95%
ILE32.N-GLN28.O 6.41%
SER47.N-THR43.O
SER47.OG-ASP160.OD2 15.95%
ARG30.NE-ASP26.OD2 6.18%
SER47.OG-THR43.OG1
ARG40.N-ILE36.O 15.77%
ARG104.NH1-GLN156.OE1 5.88%
SER53.OG-GLU55.OE1
LEU126.N-LEU122.O 15.71%
THR142.N-ASP140.OD2 5.88%
THR142.N-ASP140.OD1
GLU42.N-LEU39.O 15.47%
LYS46.NZ-GLU42.OE2 5.82%
THR142.OG1-ASP140.OD1
GLU93.N-THR89.O 15.41%
ASN103.ND2-GLU99.O 5.76%
THR143.N-ASP140.OD2
SER47.N-THR43.O 15.41%
ALA68.N-ASP71.OD2 5.76%
THR143.OG1-ASP140.OD2
ILE87.N-CYS83.O 15.29%
ARG104.N-TYR100.O 5.76%
THR149.N-ALA145.O
GLN116.NE2-GLU95.O 5.64%
THR149.OG1-ALA145.O
ARG30.NE-ASP26.OD1 5.16%
SER53.N-GLU51.OE2 5.58%
THR162.OG1-LEU158.O
THR82.OG1-ASP71.O 5.16%
GLN152.NE2-LEU148.O 5.46%
THR20.N-GLU23.OE1
SER76.OG-GLU69.OE2 5.16%
GLN28.N-ARG24.O 5.40%
THR20.OG1-GLU23.OE1
ARG113.NH2-GLU109.OE2 5.10%
ARG113.NH1-GLN102.OE1 5.34%
THR82.N-ASN79.OD1
ARG113.NH1-GLU109.OE2 5.10%
THR142.N-ASP140.OD1 5.28%
THR82.OG1-ASP71.O
THR82.OG1-ASN79.OD1 5.10%
SER53.N-GLU51.OE1 5.28%
THR89.N-VAL85.O
LYS120.NZ-GLU95.OE2 5.04%
GLN116.NE2-GLU95.OE2 5.28%
TYR100.N-VAL96.O
GLN154.NE2-LEU151.O 5.04%
ARG113.NH1-GLU109.OE1 5.28%
VAL115.N-GLN111.O
PHE125.N-VAL121.O 5.04%
LYS46.NZ-GLU42.OE1 5.22%
Table 13.7 The optimized human-IL6R-1N26-model has six .β-sheets and one helix
Sheet1-strand1_1
aa VAL15-SER18
Sheet1-strand1_2
aa THR38-ARG44
Sheet1-strand1_3
aa SER53-MET58
Sheet1-strand1_4
aa GLY73-TYR78
Sheet1-strand1_5
aa THR86-VAL91;
Sheet2-strand2_1
aa THR25-THR27
Sheet2-strand2_2
aa ARG61-LEU63;
Sheet3-strand3_1
aa SER101-PHE103
Sheet3-strand3_2
aa VAL111-TRP115
Sheet3-strand3_3
aa CYS146-SER149
Sheet3-strand3_4
aa LYS154-LEU159;
Sheet4-strand4_1
aa LYS126-PHE134
Sheet4-strand4_2
aa GLU140-PRO145
Sheet4-strand4_3
aa PHE168-ALA176
Sheet4-strand4_4
aa SER181-PHE183
Sheet4-strand4_5
aa GLN187-GLN190;
Sheet5-strand5_1
aa ALA201-ALA207
Sheet5-strand5_2
aa LEU215-GLN220
Sheet5-strand5_3
aa HIS257-ILE260;
Sheet6-strand6_1
aa LEU232-ALA240
Sheet6-strand6_2
aa THR247-MET250
Sheet6-strand6_3
aa HIS269-GLU277
Sheet6-strand6_4
aa ALA291-GLY293;
Helix_3_10
aa LEU69-ASP71
nAChRs: the human .α4β2 and .α7 subtypes and the muscle-like .αβγ δ receptor from Tetronarce californica; we denote them as .α4β2-complex, .α7-complex, and .αβγ δ-complex. The Y674-R685 peptide contains a PRRA motif, a four-residue insertion not found in other SARS-like coronaviruses (in 6VSB.pdb, the Y674R685 loop is entirely missing, whereas in 6VXX.pdb, only three residues Y674, Q675, and T676 were solved); this peptide is at the S1/S2 site (i.e., between R685 and S686) of SARS-CoV-2 spike. The peptide G381-K386 in the S1 subunit in the spike protein has also been hypothesized to interact with nAChRs, but
13.3 New Structural Bioinformatics
435
Table 13.8 All the SBs in the optimized human-IL6R-1N26-model and in the 196 .μs’ MD Opt-SBs
196 .μs-MD-SBs
ASP141-ARG132, ASP141-ARG4
ASP141-ARG132, ASP141-ARG4, ASP141-ARG5
ASP165-LYS133
ASP165-LYS133
ASP198-LYS105
ASP198-HIS223, ASP198-LYS105
ASP221-HIS256
ASP221-ARG231, ASP221-HIS256
ASP35-ARG79
ASP22-ARG65
ASP71-LYS45
ASP253-ARG231, ASP253-ARG233, ASP253-LYS252
GLU10-ARG5
ASP262-ARG213, ASP262-HIS269
GLU114-LYS154
ASP35-ARG79, ASP35-ARG82
GLU235-ARG274
ASP71-ARG44, ASP71-ARG65, ASP71-HIS51, ASP71-HIS88, ASP71-LYS45
GLU241-ARG268
GLU10-ARG13, GLU10-ARG4, GLU10-ARG5, GLU10-LYS126
GLU290-ARG239
GLU114-LYS154
GLU32-ARG79
GLU140-ARG132, GLU140-LYS133
GLU96-ARG118
GLU163-ARG104
GLU97-LYS182
GLU235-ARG274, GLU235-LYS252 GLU241-ARG239, GLU241-ARG242, GLU241-ARG268 GLU278-ARG231, GLU278-ARG233 GLU283-LYS105, GLU283-LYS185 GLU286-LYS105 GLU290-ARG239, GLU290-LYS244 GLU298-ARG210, GLU298-ARG213, GLU298-ARG268 GLU32-ARG60, GLU32-ARG79, GLU32-ARG82 GLU34-ARG60, GLU34-ARG61, GLU34-ARG79, GLU34-ARG82 GLU96-ARG118, GLU96-LYS182 GLU97-LYS182, GLU97-LYS185
glycosylation makes this unlikely. We optimized the three models and got their RMSD values 0.505718, 0.528214, and 0.468340 Å compared with the three models of [252]. The three .α4β2-, .α7-, and .αβγ δ-nAChR models (downloaded from covid.molssi.org/simulations) are built on 6UWZ.pdb, where its AD chains are the acetylcholine receptor subunit .α, B chain is the acetylcholine receptor subunit .δ, C chain is the acetylcholine receptor subunit .β, and E chain is the acetylcholine receptor subunit .γ ; our structural bioinformatics on the bindings is listed in Table 13.10, where spike’s two peptides YQTQTNSPRRAR are labeled with residue numbers 1912–1935, 1866–1889, and 1949–1972 for .α4β2, .α7, and .αβγ δ complex models, respectively, and the HBs within the peptide adopt extended conformations in the .α4β2 and .α7 complexes. All the nAChR residues that interact with the spike peptide 674YQTQTNSPRRAR685 (F chain and G chain) are as follows: ◦ .α4β2 F chain: D:TYR1339 (where there is a .π-cation linking to spike’s ARG682.NH2+), D:GLU1340 (where there exists a SB linking to spike’s residue ARG683), D:CYS1341, D:TYR1346, E:MET1559, E:SER1561, E:THR1582, E:PHE1642, E:SER1691, E:ASP1693, E:ASP1694 G chain: A:ARG188, A:LYS189, A:TYR190, A:GLU191, A:CYS192, A:TYR197, B:MET410, B:SER412, B:TRP431, B:LYS537, B:PHE493, B:SER538, B:SER542, B:LEU543, B:ASP544, B:ASP545 .◦ .α7 F chain: C:TRP1268, C:SER1269, C:TYR1270, C:ARG1305, C:PHE1306, C:TYR1307, C:GLU1308, C:CYS1309, C:TYR1314, E:SER1528, E:TRP1547, .
SER122.OG-ASP92.OD2 23.88%
VAL217.N-CYS258.O 66.17%
LYS133.NZ-ASP165.OD2
LYS154.NZ-GLU114.OE2
ALA8.N-GLU10.OE1
ARG104.NH1-SER109.O
VAL112.N-PHE103.O 52.74%
GLN272.NE2-SER288.O 50.75% CYS28.N-ARG60.O 49.75%
SER122.OG-ASP92.OD1
SER149.N-LYS154.O
ARG5.NH1-GLU10.OE2
ARG60.NH1-VAL31.O
VAL131.N-PHE142.O 51.74%
ARG274.N-GLU235.O 21.39%
GLY191.N-SER167.O 16.92%
ILE170.N-ARG132.O 47.76%
SER184.N-MET173.O 16.42% ARG118.N-GLU96.OE1 15.92% LYS154.NZ-GLU114.OE2 15.92%
LYS154.NZ-GLU114.OE1 15.42% GLN9.N-THR124.O 15.42%
CYS174.N-VAL128.O 40.30% GLU144.N-LEU129.O 38.81%
SER285.OG-GLU286.O
SER288.N-LEU273.O
SER50.OG-LYS45.O
SER76.OG-THR86.OG1
GLN190.NE2-SER166.O
GLN196.N-ARG104.O
GLN272.N-ARG237.O
GLN272.NE2-SER288.O
CYS77.N-GLY85.O 38.81%
VAL24.N-LEU64.O 40.30%
ARG239.NH2-GLU290.OE2 15.42%
LEU16.N-HIS88.O 15.92%
PHE189.N-TYR169.O 15.92%
ARG104.NH1-SER109.O 42.29% LYS182.N-VAL175.O 40.80% SER216.N-THR206.O 40.80%
SER224.OG-ASP198.OD2
SER243.N-ALA240.O
SER285.N-ALA275.O
VAL67.N-ASP22.O 15.92%
GLN147.N-SER156.O
PHE155.N-TRP115.O 43.28%
SER156.OG-GLU114.OE2 16.42%
LEU89.N-GLY73.O 16.42%
GLN276.N-ARG233.O 16.42%
SER119.N-GLU96.OE2 16.42%
SER172.N-LEU130.O 16.42%
GLN187.N-VAL171.O
CYS28.N-ARG60.O
SER149.N-LYS154.O 42.79%
SER18.OG-ASP22.OD2
SER216.N-THR206.O
CYS157.N-CYS113.O
CYS174.N-VAL128.O
LEU129.N-GLU144.O 44.28% ARG237.N-GLN272.O 44.28%
SER178.OG-ASP92.OD2
SER184.OG-LYS185.O
ASP71.OD1-LYS45.NZ
SER288.OG-PRO289.O 44.78%
LEU26.N-LEU62.O 46.77%
THR204.N-THR218.O 46.77%
CYS113.N-CYS157.O
SER177.OG-VAL93.O
SER178.N-ASP92.OD2
ASP198.OD1-LYS105.NZ
ASP35.OD2-ARG79.NH2
SER172.OG-SER184.OG
SER177.N-GLY180.O
ASN74.N-ARG44.O
ASP165.OD2-LYS133.NZ
GLN281.N-GLU277.OE2 17.41% TYR238.OH-ASP262.OD1 17.41% GLU241.N-ARG268.O 16.92%
TYR238.N-THR247.O 48.76% SER156.N-GLN147.O 48.26%
SER152.OG-SER149.OG
SER156.N-GLN147.O
SER167.OG-ASP165.OD1
ARG79.NH2-ASP35.OD2
ASN110.ND2-GLN158.OE1
VAL208.N-TRP214.O 17.91%
ARG44.N-ASN74.O 18.41%
LEU43.N-SER53.O 18.91%
LYS133.N-GLU140.O 18.91%
HIS269.N-GLY293.O 18.91%
ARG239.NH2-GLU290.OE1 19.40%
GLY293.N-HIS269.O 19.40%
GLY59.N-ALA37.O 20.40%
PHE103.N-VAL112.O 20.40%
ASN202.ND2-GLN220.OE1
ALA275.N-SER285.OG 50.75%
TYR169.N-PHE189.O 51.74%
PHE279.N-GLU277.OE2
SER101.N-GLU114.O
ARG268.NH2-GLU241.OE1
VAL175.N-LYS182.O 52.24%
SER72.OG-GLN68.O 52.74%
ARG233.N-GLN276.O 52.74%
VAL39.N-GLY57.O 55.72%
ARG44.N-ASN74.O
PHE142.N-VAL131.O
PHE155.N-TRP115.O
ARG239.NH2-GLU290.OE2
ARG268.NE-GLU241.OE2
PHE103.N-VAL112.O
PHE134.N-PHE168.O
ARG239.N-VAL270.O
VAL128.N-CYS174.O 53.73%
LYS45.NZ-ASP71.OD1
LYS45.NZ-HIS70.O
ARG233.N-GLN276.O
ARG237.N-GLN272.O
ARG239.NE-GLU290.OE1
CYS102.N-GLN187.OE1 23.38% THR125.N-SER122.O 23.38% ALA201.N-GLN220.O 22.89%
SER285.N-ALA275.O 63.68% ILE260.N-LEU215.O 62.69% LEU130.N-SER172.O 61.69%
LYS182.N-VAL175.O
LYS182.NZ-GLU97.OE1
LYS185.NZ-GLN99.OE1
ARG118.N-GLU96.OE2
SER119.OG-GLU96.OE2 23.88%
PHE142.N-VAL131.O 24.38%
VAL42.N-SER76.O 65.17%
VAL171.N-GLN187.O 75.12%
ARG231.N-GLU278.OE1
ARG104.NH2-PRO162.O
SER177.N-GLY180.O 23.88%
VAL270.N-ARG239.O 68.16%
LYS126.N-ALA176.O
LYS126.NZ-LEU123.O
ALA275.N-SER285.OG
GLN187.N-VAL171.O 24.88% SER119.OG-GLU96.OE1 24.88%
ALA37.N-ASP35.OD1
SER285.OG-GLU286.O 79.10% VAL271.N-ALA291.O 75.12%
LYS105.NZ-ASP198.OD1
ALA176.N-LYS126.O
196 .μs-MD-HBs
LEU90.N-LEU16.O
ALA160.N-GLU144.OE2
Opt-HBs
Table 13.9 The HBs (with occupancy rates .≥5%) of the human-IL6R-1N26-model during 196 .μs’ MD THR124.OG1-ASP92.OD2 10.95%
(continued)
ARG79.NH1-ASP35.OD1 8.46%
ARG268.NH2-GLU241.OE1 8.46%
TRP115.N-PHE155.O 8.46%
SER167.N-ASP165.OD2 8.46%
ARG231.NH2-GLU278.OE1 8.46%
ARG79.NH2-ASP35.OD1 8.46%
ARG79.N-PRO83.O 8.46%
LYS105.NZ-ASP198.OD1 8.46%
TRP225.NE1-TYR230.O 8.96%
SER76.OG-THR86.OG1 8.96%
ARG79.NH1-ASP35.OD2 8.96%
PHE168.N-PHE134.O 8.96%
ARG118.N-GLU96.OE2 9.45%
VAL179.N-ASP92.OD2 9.45%
THR124.OG1-SER177.OG 9.45%
SER265.OG-GLU298.OE1 9.45%
ARG268.NH2-GLU241.OE2 9.45%
GLN135.N-SER137.O 9.95%
ARG231.NE-GLU278.OE1 9.95%
PHE279.N-GLU277.OE2 9.95%
SER181.OG-CYS6.O 9.95%
LYS182.NZ-PRO95.O 9.95%
CYS146.N-ALA127.O 9.95%
GLN9.NE2-LEU123.O 9.95%
SER177.OG-ASP92.OD1 9.95%
ARG274.NH2-GLU235.OE1 9.95%
GLN276.NE2-GLY282.O 10.45%
TYR78.N-HIS40.O 10.45%
GLN99.NE2-GLU97.O 10.45%
PHE279.N-GLU277.OE1 10.45%
SER167.N-ASP165.OD1 10.45%
GLY21.N-VAL67.O 10.45%
THR125.OG1-SER122.O 10.95%
GLU283.N-LEU195.O 10.95%
ALA291.N-VAL271.O 10.95%
GLU235.N-ARG274.O 10.95%
436 13 Human ACE2, Human IL6, Human IL6R, and Human nAChRs
THR125.OG1-SER122.OG
THR204.N-THR218.O
THR206.N-SER216.O
TRP225.N-PRO222.O
TRP225.NE1-TYR230.O
TRP249.N-LEU236.O
TRP287.N-GLU286.OE1
TRP41.N-TRP55.O
TRP55.N-TRP41.O
TYR148.OH-GLN153.OE1
TYR169.N-PHE189.O
TYR169.OH-ALA160.O
TYR230.OH-GLU163.OE2
TYR238.OH-ASP262.OD2
TYR75.N-VAL87.O
VAL112.N-PHE103.O
VAL131.N-PHE142.O
VAL171.N-GLN187.O
VAL175.N-LYS182.O
VAL217.N-CYS258.O
VAL251.N-PHE234.O
VAL270.N-ARG239.O
VAL271.N-ALA291.O
VAL39.N-GLY57.O
VAL42.N-SER76.O
VAL87.N-TYR75.O
VAL91.N-SER72.OG
GLN281.N-GLU277.OE1
GLN281.NE2-GLU163.OE1
GLN68.NE2-SER66.O
GLU10.OE2-ARG5.NH1
GLU114.N-SER101.O
GLU140.N-LYS133.O
GLU151.N-GLU151.OE2
GLU235.N-ARG274.O
GLU241.N-ARG268.O
GLU241.OE1-ARG268.NH2
GLU241.OE2-ARG268.NE
GLU290.OE2-ARG239.NH2
GLU32.N-GLU32.OE2
GLU34.N-GLU34.OE2
GLU97.OE1-LYS182.NZ
GLY164.N-GLU163.OE1
GLY21.N-VAL67.O
GLY280.N-GLU277.OE1
GLY293.N-HIS269.O
GLY57.N-VAL39.O
GLY59.N-ALA37.O
GLY73.N-LEU89.O
HIS256.NE2-ASP221.OD2
HIS269.N-GLY293.O
HIS269.NE2-TRP264.O
ILE170.N-ARG132.O
196 .μs-MD-HBs
HIS88.N-GLY14.O 5.47% ARG231.N-GLU278.OE1 5.47%
LEU64.N-VAL24.O
LEU89.N-GLY73.O
ARG231.NH2-GLU278.OE2 5.97% TRP214.N-ASN211.OD1 5.97%
THR124.OG1-SER178.OG 5.97%
ASP35.N-GLU32.O 5.97%
LEU273.N-SER288.OG
GLU278.N-ARG231.O 11.44%
LEU215.N-ILE260.O
SER72.N-GLN68.O 5.97%
LEU43.N-SER53.O
ARG104.NE-ILE194.O 11.44%
LEU19.N-ASP22.OD2
LEU1.N-ASP141.OD2 5.97%
ALA37.N-ASP35.OD2 5.97%
SER18.N-LEU90.O 11.44%
LEU16.N-HIS88.O
SER101.OG-LEU100.O 5.97%
LEU267.N-TRP264.O 5.97%
SER109.OG-SER106.O 5.97%
SER177.OG-VAL93.O 6.47%
GLN99.NE2-GLU97.OE2 6.47%
GLY85.N-CYS77.O 6.47%
GLN255.NE2-HIS257.O 6.47%
GLN99.NE2-GLU97.OE1 6.47%
GLN281.NE2-GLU277.OE1 6.97%
ARG231.N-GLU278.OE2 6.97%
GLY280.N-GLU277.O 6.97%
ILE194.N-GLN190.O 6.97%
ALA37.N-ASP35.OD1 6.97%
GLN196.N-LYS105.O 6.97%
LEU236.N-TRP249.O 6.97%
LYS105.NZ-ASP198.OD2 7.46%
ARG104.NH2-PRO162.O 7.46%
SER66.N-ASP22.O 7.46%
HIS257.NE2-SER216.OG 7.46%
VAL251.N-PHE234.O 7.46%
SER177.OG-ASP92.OD2 7.46%
ARG213.NE-ALA263.O 7.46%
THR125.OG1-SER122.OG 7.46%
GLN9.N-SER177.O 7.46%
VAL179.N-ASP92.OD1 7.96%
GLN187.NE2-LEU100.O 7.96%
ALA139.N-LYS133.O 7.96%
ARG239.N-VAL270.O 7.96%
SER243.N-ALA240.O 7.96%
GLN220.N-ALA201.O 8.46%
LEU236.N-TRP249.O
ARG231.NE-GLU278.OE2 11.44%
LEU130.N-SER172.O
SER178.OG-ASP92.OD1 11.44%
ASN202.ND2-GLN220.OE1 11.94%
GLN281.NE2-GLU277.OE2 11.94%
GLY57.N-VAL39.O 11.94%
GLU114.N-SER101.O 11.94%
LEU215.N-ILE260.O 11.94%
HIS40.N-TYR78.O 11.94%
LEU159.N-VAL111.O 12.44%
ARG268.NE-GLU241.OE1 12.44%
GLN281.N-GLU277.OE1 12.44%
THR124.OG1-ASP92.OD1 12.94%
ARG237.NH2-GLN272.OE1 12.94%
TRP55.N-TRP41.O 13.43%
SER156.OG-GLU114.OE1 13.43%
ASP92.N-SER18.O 13.43%
SER265.OG-GLU298.OE2 13.43%
GLN196.NE2-TRP284.O 13.93%
SER178.OG-ASP92.OD2 13.93%
TYR238.OH-ASP262.OD2 13.93%
THR86.OG1-SER76.OG 13.93%
THR120.OG1-GLN153.OE1 13.93%
TYR148.OH-GLN150.OE1 13.93%
ARG132.N-ILE170.O 13.93%
ARG268.NE-GLU241.OE2 14.43%
SER18.OG-LEU90.O 14.43%
ARG274.NH2-GLU235.OE2 14.43%
CYS258.N-VAL217.O 14.93%
TYR75.N-VAL87.O 14.93%
SER119.N-GLU96.OE1 14.93%
ARG213.N-ASN211.OD1 11.44%
MET173.N-SER184.OG 25.37%
SER224.OG-ASP198.OD1 25.87%
GLN272.N-ARG237.O 25.87%
SER122.OG-ASP92.OD1 26.87%
THR206.N-SER216.O 27.36%
PHE134.N-PHE168.O 27.36%
GLN147.N-SER156.O 27.86%
THR218.N-THR204.O 28.36%
SER224.OG-ASP198.OD2 28.86%
SER184.OG-LYS185.O 29.85%
TRP249.N-LEU236.O 30.35%
GLN190.NE2-SER166.O 30.35%
ALA176.N-LYS126.O 30.35%
CYS113.N-CYS157.O 31.34%
TRP41.N-TRP55.O 32.84%
VAL111.N-LEU159.O 33.33%
VAL87.N-TYR75.O 33.83%
SER76.N-VAL42.O 33.83%
SER167.OG-ASP165.OD2 34.33%
LEU62.N-LEU26.O 34.33%
LEU273.N-SER288.OG 34.83%
SER167.OG-ASP165.OD1 34.83%
LEU64.N-VAL24.O 34.83%
SER288.N-LEU273.O 35.32%
LYS126.N-ALA176.O 37.31%
GLN196.N-ARG104.O 37.81%
CYS157.N-CYS113.O 38.31%
LEU90.N-LEU16.O 38.31%
THR247.N-TYR238.O 38.81%
LEU129.N-GLU144.O
ILE260.N-LEU215.O
THR124.OG1-ASP92.OD2
GLN276.N-ARG233.O
GLN276.NE2-GLY282.O
Opt-HBs
Table 13.9 (continued)
13.3 New Structural Bioinformatics 437
438
13 Human ACE2, Human IL6, Human IL6R, and Human nAChRs
Table 13.10 The HBs and SBs of the three nicotinic acetylcholine receptors (nAChRs) linking to the spike peptide YQTQTNSPRRAR .α4β2
.α7
.αβγ δ
F:ALA1922.N-D:GLU1340.OE2
G:ALA1888.N-A:GLU189.OE1
F:ASN1954.ND2-B:ASP543.OD1
D:GLU1340-F:ARG1921
G:ASN1883.ND2-B:ASP537.OD2
B:ASP543-F:ARG1958
G:ALA1934.N-A:GLU191.OE2
D:ARG1305.NH1-F:GLN1867.OE1
A:TYR190.OH-F:GLN1950.OE1
F:ARG1874.NH1-F:GLN1869.OE1
G:TYR1961.N-E:ASP1730.OD2
F:GLN1869.NE2-F:THR1868.OG1
G:GLN1962.NE2-E:ASP1733.OD2
F:THR1951.N-B:ASP558.OD2 G:GLN1925.NE2-B:ASP544.OD2 G:THR1926.N-B:ASP544.OD1 F:GLN1915.NE2-F:THR1914.O
E:GLU1720-G:ARG1970
G:GLN1925.N-G:THR1928.OG1 G:GLN1964.NE2-G:THR1963.OG1
E:GLN1549, E:GLN1609, E:GLN1651, E:MET1652, E:ASP1656, E:SER1658, E:GLY1659 G chain: A:TRP149, A:SER150, A:PHE187, A:TYR188, A:GLU189, A:CYS190, A:TYR195, B:SER409, B:GLN430, B:GLN490, B:ASP537, B:SER539, B:GLY540 .◦ .αβγ δ F chain: A:VAL88, A:TYR189, A:TYR190, A:THR191, A:CYS192, A:TYR198, B:THR416, B:TRP435, B:ASP437, B:LEU499, B:MET541, B:THR542, B:ASP543 (where there exists a SB linking to spike’s residue ARG683), B:THR544, B:ILE545, B:ILE552, B:ILE556, B:ASP558, B:PRO559, B:GLU560 G chain: D:TRP1326, D:VAL1365, D:TYR1366, D:TYR1367, D:THR1368, D:CYS1369, D:TYR1375, E:LYS1590, E:THR1592, E:TYR1667, E:TRP1611, E:GLU1613, E:GLN1615, E:TYR1673, E:GLU1719, E:GLU1720 (where there exists a SB linking to spike’s residue ARG683), E:HID1728, E:ASP1730, E:GLU1732, E:ASP1733 We can see the chains which bind F-chain YQTQTNSPRRAR are DE-chains, CE-chains, and AB-chains of .α4β2, .α7, and .αβγ δ models, respectively, and the chains which bind G-chain YQTQTNSPRRAR are AB-chains, AB-chains, and DEchains of .α4β2, .α7, and .αβγ δ models, respectively (Table 13.10 too). In addition to the observation of [252], we not only find the G-chain YQTQTNSPRRAR Y674R685 penetrates deeply into the binding pocket of .α7 but also find it penetrates deeply into the binding pocket of .αβγ δ.
13.4 Concluding Remarks This chapter studies the three models human-ACE2-6LZG-model, human-IL61ALU-model, and human-IL6-1ALU-model for the fighting against SARS-CoV-2. The human-ACE2-6LZG-model has strong polar contacts GLU166-HIS493, GLU227-LYS458, GLU189-LYS112, GLU181-LYS470, GLU398-ARG514, GLU435-LYS541, ASP509-LYS187, GLU406-ARG518, GLU37-ARG393, and GLU435-HIS540 during the long MD simulation, and a large variable segment PRO492-LEU503 unfolds from .α-helix into 3.10 -helix and turns, and the model
13.4 Concluding Remarks
439
Fig. 13.7 The SBs GLU435-LYS541, ASP509-LYS187, GLU166-HIS493, GLU189-LYS112, GLU406-ARG518, GLU435-HIS540, GLU37-ARG393, GLU181-LYS470, GLU227-LYS458, GLU398-ARG514, GLU430-LYS541, ASP38-LYS353, ASP382-HIS401, ASP431-LYS288, ASP543-LYS416, GLU433-LYS288, and GLU549-LYS534 spanning a large number of residues of the human-ACE2-6LZG-model during the 664 μs’ MD
440
Fig. 13.7 (continued)
13 Human ACE2, Human IL6, Human IL6R, and Human nAChRs
13.4 Concluding Remarks
441
Fig. 13.8 The SBs GLU110-ARG113, GLU80-LYS129, GLU95-LYS120, ASP160-ARG104, ASP26-ARG30, ASP71-LYS70, ASP71-LYS86, GLU42-LYS46, and GLU51-ARG40 of the human-IL6-1ALU-model during the 1593 μs’ MD
442
13 Human ACE2, Human IL6, Human IL6R, and Human nAChRs
Fig. 13.9 The SBs ASP35-ARG79, ASP198-LYS105, GLU114-LYS154, GLU235-ARG274, GLU241-ARG268, GLU290-ARG239, ASP71-LYS45, ASP141-ARG4, and ASP221-HIS256 of the human-IL6R-1N26-model during the 196 μs’ MD
13.4 Concluding Remarks
443
has large areas of negative charges of Poisson-Boltzmann electrostatic potential surfaces. The human-IL6-1ALU-model has strong SBs GLU110-ARG113, GLU80LYS129, GLU95-LYS120, ASP160-ARG104, ASP26-ARG30, ASP71-LYS70, ASP71-LYS86, GLU42-LYS46, and GLU51-ARG40 during the long MD simulation; during the long MD, we should also notice the stronger HBs between ARG182 and ASP26, ARG182.NE-ASP26.OD1 14.81%, ARG182.NE-ASP26.OD2 13.19%, ARG182.NH2-ASP26.OD1 13.07%, and ARG182.NH2-ASP26.OD2 12.77%, and the stronger HBs between SER47 and ASP160: SER47.OG-ASP160.OD2 15.95% and SER47.OG-ASP160.OD1 14.33%; the Poisson-Boltzmann electrostatic potential surfaces of the optimized human-IL6-1ALU-model have large areas of positive charges. The optimized human-IL6R-1N26-model has six .α-sheets and one 3.10 -helix; the Poisson-Boltzmann electrostatic potential surfaces of the optimized human-IL6R-1N26-model have large positive charges; SBs ASP35-ARG79, ASP198-LYS105, GLU114-LYS154, GLU235-ARG274, GLU241-ARG268, GLU290-ARG239, ASP71-LYS45, ASP141-ARG4, and ASP221-HIS256 are important to maintain the structural stability of the human-IL6R-1N26-model. Human .α4β2-, .α7-, and .αβγ δ-nAChRs binding SARS-CoV-2 spike Y674-R685 region are also studied in this chapter.
Chapter 14
PLpro Binding with 12 Compounds
Abstract The papain-like protease (PLpro), a component of the large, multidomain protein NSP3, is a cysteine protease essential for the replication of coronaviruses and thus a potential target for antivirals. This chapter confirms a binding site consisting of .α-helices 5 and 8 and the strands 1, 2, 3, 4, and 7 of .β-sheet-4 of PLpro monomer. Keywords MD and optimization studies · SARS-CoV-2 PLpro · PLpro-binding site · Top compounds · Drug designing or discovery
14.1 Introduction The papain-like protease (PLpro), a component of the large, multi-domain protein NSP3, is a cysteine protease essential for the replication of coronaviruses and thus a potential target for antivirals. In [321], it is suggested that the Gly165-Gly273 pocket could be potentially exploited as an interaction site for small-molecule inhibitors and 12 compounds were presented in [321]. This chapter is to optimize and then MD-study these 12 compounds.
14.2 Materials and Methods The 5- or 2-microsecond simulation MD trajectories in [321] of PLpro bound to 12 rationally designed inhibitors will be used in this chapter. We denote the datasets as the following 12 models: Model1-DESRES-ANTON-11730054T1-08, Model2-DESRES-ANTON-11730063-T1-04, Model3-DESRES-ANTON11730068, Model4-DESRES-ANTON-11738401-T1-05, Model5-DESRESANTON-11738463-T1-06, Model6-DESRES-ANTON-11738465-T2-01, Model7DESRES-ANTON-11738466-T1-07, Model8-DESRES-ANTON-12330576-T111, Model9-DESRES-ANTON-12330880-T2-02, Model10-DESRES-ANTON12346144, Model11-DESRES-ANTON-12346145-T1-10, and Model12-DESRESANTON-12346146-T1-09. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_14
445
446
14 PLpro Binding with 12 Compounds
14.3 Results and Discussions Seeing Fig. 14.1, Table 14.1, and Fig. 14.2, we may know the binding residues are in regions aa 110–113, aa 158–168, residue 209, aa 246–249, aa 265–274, and aa 302–303, i.e., .α-helices 5 and 8 and the strands 1, 2, 3, 4, and 7 of .β-sheet-4. In this binding site, there are SBs ASP287-HIS273 (with HBs ASP287.N-HIS290.O 44.00% 1, 43.40% 2, 42.80% 4, 48.20% 5, 40.80% 6, 48.60% 7, 45.00% 8, 43.00% 9, 41.00% 10, 47.00% 11, and 43.50% 12: Tables 14.2, 14.3, 14.4, and 14.5), GLU264-ARG285 (with HBs ARG285.NE-GLU264.OE2 31.40% 1, NEOE1 35.50% 2, NE-OE2 29.20% 5, NH2-OE1 32.00% 6, NE-OE1 28.80% 7, NH2-OE2 31.50% 10, and NH2-OE2 31.00% 12: Tables 14.2, 14.3, 14.4, and 14.5), ASP165-ARG167, GLU162-LYS158 (with HB LYS158.NZ-LEU163.O 31.50% 11: Tables 14.2, 14.3, 14.4, and 14.5), GLU168-LYS158, and GLU168-ARG167 to maintain its structural stability.
Fig. 14.1 The ligands’ interaction diagrams for the 12 optimized models
Table 14.1 The HBs with more than 30% occupancy rates from the analyses of the 100 .μs’ MD trajectory data of [321] The model
Residues in the binding site
Model1-DESRES-ANTON-11730054-T1-08-optimized
163, 164, 165, 167, 168, 248, 249, 265, 267, 268, 269, 270, 271, 274, 302, 317
Model2-DESRES-ANTON-11730063-T1-04-optimized
158, 163, 164, 165, 167, 168, 209, 248, 249, 265, 267, 268, 269, 270, 274, 317
Model3-DESRES-ANTON-11730068-optimized
163, 164, 165, 166, 167, 168, 209, 246, 247, 248, 249, 265, 268, 269, 270, 271, 272, 274, 302, 303, 317
Model4-DESRES-ANTON-11738401-T1-05-optimized
163, 164, 165 168, 248, 249, 265, 267, 268, 269, 270, 271, 272, 274, 302, 317
Model5-DESRES-ANTON-11738463-T1-06-optimized
110, 113, 163, 164, 165, 167, 168, 209, 248, 249, 265, 267, 268, 269, 270, 272, 274, 302, 317
Model6-DESRES-ANTON-11738465-T2-01-optimized
110, 112, 113, 163, 164, 165, 167, 168, 248, 249, 265, 267, 268, 269, 270, 272, 273, 274, 317
Model7-DESRES-ANTON-11738466-T1-07-optimized
110, 112, 113, 163, 164, 165, 167, 168, 249, 265, 268, 269, 270, 272, 274, 302, 317
Model8-DESRES-ANTON-12330576-T1-11-optimized
110, 112, 113, 163, 164, 165, 168, 209, 247, 248, 249, 267, 268, 269, 270, 272, 273, 274, 302, 317
Model9-DESRES-ANTON-12330880-T2-02-optimized
110, 112, 113, 163, 164, 165, 167, 168, 248, 249, 265, 267, 268, 269, 270, 272, 273, 274, 302, 317
v Model10-DESRES-ANTON-12346144-optimized
158, 163, 164, 165, 168, 248, 249, 265, 267, 268, 269, 270, 274, 302, 317
Model11-DESRES-ANTON-12346145-T1-10-optimized
158, 163, 164, 165, 248, 249, 265, 269, 270, 274, 302, 317
Model12-DESRES-ANTON-12346146-T1-09-optimized
158, 163, 164, 165, 167, 168, 209, 248, 249, 265, 268, 269, 270, 271, 274, 302, 317
14.3 Results and Discussions
447
For the PLpro monomer, it is interesting to see the positively charged HIS, LYS, and ARG residues such as HIS+192, LYS+191, LYS+196, ARG+229, LYS+218, LYS+293, HIS+290, LYS+95, LYS+93, HIS+48, LYS+46, and LYS+44 are distributed onto the boundary of the Poisson-Boltzmann electrostatic potential surface (Fig. 14.3 with blue colors). For the 5 or 2 .μs’ MDs of the 12 PLpro monomer models, seeing the MD secondary structures and RMSF performance in Fig. 14.4, we may know the 3.10 helices 1 and 9 and the 5th strand of .β-sheet-3 have secondary structure changes during the MD and the N-terminal residues before .α-helix-3 (including .β-sheet-1 with five strands, .α-helix-1, and .α-helix-2) have larger RMSF values.
Fig. 14.2 The .α-helices’ and .β-sheets’ 3D structure of the PLpro monomer model, where the circle including .α-helices 5 and 8 and the strands 1, 2, 3, 4, and 7 of .β-sheet-4 is the binding site for the 12 ligands
Fig. 14.3 The Poisson-Boltzmann electrostatic potential surface diagram for the PLpro monomer model
448
14 PLpro Binding with 12 Compounds
14.4 Concluding Remarks The papain-like protease (PLpro), a component of the large, multi-domain protein NSP3, is a cysteine protease essential for the replication of coronaviruses and thus a potential target for antivirals. This chapter confirms a binding site consisting of .α-helices 5 and 8 and the strands 1, 2, 3, 4, and 7 of .β-sheet-4 of PLpro monomer. The binding site residues are aa 110, 112, 113, 58, 163, 164, 165, 167, 168, 209, 246, 247, 248, 249, 265, 267, 268, 269, 270, 271, 272, 273, 274, 302, and 303 of PLpro.
Fig. 14.4 The MD secondary structures and RMSF graphs for the PLpro monomer model
Model numbers
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 with HBs ASP287.N-HIS290.O 44% 1, 43.4% 2, 42.8% 4, 48.2% 5, 40.8% 6, 48.6% 7, 45% 8, 43% 9, 41% 10, 47% 11, 43.5% 12
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 with HBs ARG285.NE-GLU264.OE2 31.4% 1, NE-OE1 35.5% 2, NE-OE2 29.2% 5, NH2-OE1 32% 6, NE-OE1 28.8% 7, NH2-OE2 31.5% 10, NH2-OE2 31% 12
1, 3, 4, 7, 9, 10, 11
8
2, 4, 5, 6, 7, 10, 11, 12
1, 2, 6, 7, 9, 11, 12
3, 5
5
1, 3, 5, 6, 8, 9, 10, 12
1, 2, 3, 4, 5, 6, 7, 9, 12
2, 3, 4, 7, 9, 11
1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12
1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12
3, 5, 7
4, 8
1, 2, 3, 4, 5, 9, 11, 12
1, 2, 4, 5, 6, 7, 8, 9, 10, 12
3, 4, 6, 7, 8, 9, 10, 11, 12
1, 4, 8, 10, 11
3, 6, 9, 10, 12
1, 4, 5, 6, 7, 9, 12 with HB LYS158.NZ-LEU163.O 31.5% 11
3, 10, 11
1, 5, 8, 9, 11, 12
8
9, 11, 12
1, 2, 5, 6, 7, 8, 9, 11, 12
2, 3, 5, 8, 9, 11, 12
4
2, 9
5
1, 3, 9
SBs
ASP287-HIS273
ASP77-ARG83
GLU239-LYS183
GLU251-LYS298
GLU264-ARG285
ASP230-LYS191
ASP230-ARG229
ASP38-LYS92
GLU125-LYS307
GLU125-LYS127
GLU125-ARG141
GLU281-LYS293
GLU296-LYS253
GLU78-ARG66
ASP144-ARG139
ASP215-LYS218
ASP109-HIS90
ASP109-LYS93
ASP165-ARG167
ASP287-ARG285
ASP41-LYS44
ASP63-ARG66
GLU135-ARG139
GLU162-LYS158
GLU168-LYS158
GLU168-ARG167
GLU180-LYS127
GLU281-LYS280
GLU2-LYS4
GLU52-LYS7
GLU52-LYS4
GLU68-HIS18
GLU296-LYS253
GLU308-LYS218
Table 14.2 The SBs of the optimized models [321]:
14.4 Concluding Remarks 449
450
14 PLpro Binding with 12 Compounds
Table 14.3 The HBs with more than 30% occupancy rates from the analyses of the 5 .μs’ MD trajectory data of [321] Model1-optimized
Model2-optimized
Model3-optimized
Model4-optimized
MET244.N-VAL206.O 73.00%
TYR155.N-LEU151.O 73.00%
MET245.N-VAL304.O 73.00%
LEU118.N-LEU114.O 69.40%
TYR155.N-LEU151.O 67.60%
PHE56.N-PHE9.O 68.60%
TYR265.OH-ASN268.O 70.80%
TYR73.OH-VAL12.O 68.40%
ILE286.N-HIS276.O 67.40%
LEU118.N-LEU114.O 68.20%
MET244.N-VAL206.O 69.80%
PHE56.N-PHE9.O 68.40%
PHE56.N-PHE9.O 66.80%
MET245.N-VAL304.O 68.00%
LEU174.N-MET170.O 69.80%
TYR155.N-LEU151.O 66.60%
LEU200.N-ARG184.O 66.00%
TYR84.OH-ASN147.OD1 68.00%
PHE56.N-PHE9.O 66.60%
TYR265.OH-ASN268.O 66.40%
MET245.N-VAL304.O 63.40%
LEU200.N-ARG184.O 65.60%
TYR84.N-PHE80.O 66.40%
ILE286.N-HIS276.O 66.20%
LYS106.N-LYS95.O 62.40%
TYR73.OH-VAL12.O 65.00%
PHE32.N-TYR28.O 64.80%
MET244.N-VAL206.O 65.00%
PHE305.N-CYS261.O 61.80%
ILE286.N-HIS276.O 64.80%
TYR155.N-LEU151.O 64.60%
LEU200.N-ARG184.O 63.80%
MET170.N-VAL166.O 60.80%
PHE305.N-CYS261.O 63.40%
LEU200.N-ARG184.O 63.80%
MET245.N-VAL304.O 63.80%
TYR265.OH-ASN268.O 60.60%
MET170.N-VAL166.O 63.00%
PHE305.N-CYS261.O 62.20%
PHE305.N-CYS261.O 62.40%
PHE32.N-TYR28.O 60.00%
MET244.N-VAL206.O 62.60%
TYR73.OH-VAL12.O 61.20%
LYS106.N-LYS95.O 62.20%
TYR84.N-PHE80.O 57.80%
ALA140.N-ALA136.O 62.00%
TYR84.OH-ASN147.OD1 59.00%
GLU135.N-PRO131.O 61.20%
MET85.N-LEU81.O 55.60%
PHE32.N-TYR28.O 58.00%
LEU121.N-VAL117.O 58.80%
TYR84.OH-ASN147.OD1 61.00%
LEU121.N-VAL117.O 54.80%
ARG184.NE-GLN238.OE1 57.60%
LYS106.N-LYS95.O 58.80%
PHE32.N-TYR28.O 61.00%
LEU118.N-LEU114.O 54.40%
TYR84.N-PHE80.O 57.60%
GLN238.NE2-ALA205.O 58.80%
GLN238.NE2-ALA205.O 57.80%
ASN187.N-TYR234.O 53.80%
VAL8.N-GLN20.O 57.40%
LEU118.N-LEU114.O 58.60%
TYR84.N-PHE80.O 57.80%
THR169.OG1-ASP165.O 53.80%
LYS106.N-LYS95.O 56.40%
ARG184.NE-GLN238.OE1 57.40%
ALA140.N-ALA136.O 57.20%
v VAL8.N-GLN20.O 52.80%
LEU174.N-MET170.O 55.80%
THR302.OG1-ASP303.OD2 57.00%
MET170.N-VAL166.O 56.40%
LEU174.N-MET170.O 52.40%
LEU119.N-SER115.O 55.60%
PHE128.N-GLN134.OE1 55.20%
THR302.N-ASN263.O 55.20%
GLN20.N-VAL8.O 51.60%
THR302.N-ASN263.O 55.20%
LYS307.N-THR258.O 55.00%
VAL8.N-GLN20.O 54.60%
ARG141.N-TYR137.O 51.20%
GLU135.N-PRO131.O 54.60%
ARG141.N-TYR137.O 54.20%
GLU264.N-THR275.O 54.40%
THR35.OG1-GLY33.O 51.00%
LEU88.N-TYR84.O 53.60%
ARG285.N-THR292.O 54.00%
ARG285.N-THR292.O 53.20%
TYR73.OH-VAL12.O 50.60%
ILE152.N-PHE148.O 53.20%
ILE286.N-HIS276.O 54.00%
GLY220.N-ASN216.O 52.80%
ASN263.N-ASP303.O 50.00%
VAL99.N-LEU102.O 52.00%
ALA140.N-ALA136.O 53.40%
LEU121.N-VAL117.O 52.40%
LEU88.N-TYR84.O 49.80%
GLN238.NE2-ALA205.O 51.60%
THR35.OG1-GLY33.O 53.40%
LEU119.N-SER115.O 51.60%
ARG184.NE-GLN238.OE1 49.80%
ASN187.N-TYR234.O 51.20%
LEU88.N-TYR84.O 52.40%
ASN187.N-TYR234.O 50.60%
LEU119.N-SER115.O 49.80%
LEU124.N-ALA120.O 50.00%
GLN20.N-VAL8.O 51.80%
ILE152.N-PHE148.O 50.40%
PHE128.N-GLN134.OE1 49.20%
SER104.N-PRO97.O 49.80%
VAL8.N-GLN20.O 51.60%
ARG184.NE-GLN238.OE1 50.00%
GLN238.NE2-ALA205.O 48.60%
THR35.OG1-GLY33.O 49.80%
GLN122.NE2-LEU118.O 51.20%
VAL99.N-LEU102.O 49.60%
GLU264.N-THR275.O 48.60%
PHE128.N-GLN134.OE1 49.80%
ILE223.N-ALA231.O 50.20%
MET85.N-LEU81.O 49.60%
SER104.N-PRO97.O 48.40%
TYR284.N-THR278.O 49.40%
ILE277.N-ALA262.O 50.00%
THR103.N-GLN122.OE1 49.40%
ARG285.N-THR292.O 48.40%
GLN122.NE2-THR103.O 49.20%
VAL304.N-MET245.O 50.00%
PHE128.N-GLN134.OE1 49.40%
VAL221.N-GLN233.O 48.40%
GLU264.N-THR275.O 49.00%
LEU119.N-SER115.O 49.60%
GLN122.NE2-THR103.O 49.20%
VAL304.N-MET245.O 47.40%
MET85.N-LEU81.O 48.80%
MET170.N-VAL166.O 48.80%
TYR284.N-THR278.O 49.00%
TYR155.OH-TYR73.O 46.60%
THR103.N-GLN122.OE1 48.60%
GLN233.N-VAL221.O 48.20%
THR91.N-ALA87.O 49.00%
MET24.N-LYS4.O 46.40%
ASN178.N-LYS127.O 48.40%
MET85.N-LEU81.O 47.80%
LEU174.N-MET170.O 48.80%
THR302.N-ASN263.O 46.40%
GLN20.N-VAL8.O 48.20%
THR278.N-TYR284.O 47.20%
VAL304.N-MET245.O 48.60%
GLY220.N-ASN216.O 46.40%
THR169.OG1-ASP165.O 47.60%
LEU260.N-PHE305.O 47.20%
GLN122.NE2-LEU118.O 48.60%
TYR265.N-PRO300.O 46.20%
THR91.N-ALA87.O 47.20%
VAL99.N-LEU102.O 47.20%
LEU88.N-TYR84.O 48.20%
VAL189.N-THR232.O 46.00%
ARG285.N-THR292.O 47.00%
THR169.N-ASP165.O 46.00%
THR35.OG1-GLY33.O 47.40%
GLN122.NE2-LEU118.O 45.80%
GLY220.N-ASN216.O 46.80%
TYR284.N-THR278.O 46.00%
LEU260.N-PHE305.O 46.60%
TYR284.N-THR278.O 45.60%
TYR155.OH-TYR73.O 46.60%
VAL189.N-THR232.O 45.80%
GLN20.N-VAL8.O 45.20%
ASN178.N-LYS127.O 45.00%
THR171.OG1-ARG167.O 46.60%
ASN187.N-TYR234.O 45.60%
ILE277.N-ALA262.O 45.20%
ALA140.N-ALA136.O 44.60%
LEU151.N-ASN147.O 45.80%
TYR265.N-PRO300.O 44.80%
ASN129.N-HIS176.O 44.80%
VAL185.N-GLN237.O 44.60%
MET24.N-LYS4.O 45.60%
SER104.N-PRO97.O 44.60%
TYR155.OH-TYR73.O 44.80%
ILE277.N-ALA262.O 44.20%
ALA132.N-TYR72.O 45.60%
LEU37.N-ALA40.O 44.60%
ALA132.N-TYR72.O 44.80%
ASP287.N-HIS290.O 44.00%
THR198.N-LEU186.O 45.20%
TYR208.OH-GLN233.OE1 44.60%
PHE70.N-ARG66.O 43.80%
VAL189.N-THR232.O 44.40%
THR302.N-ASN263.O 44.20%
VAL189.N-THR232.O 44.00%
TYR306.OH-LEU212.O 43.80%
GLN122.NE2-LEU118.O 44.20%
ILE152.N-PHE148.O 44.00%
VAL188.N-LYS196.O 43.80%
TYR265.N-PRO300.O 44.20%
VAL188.N-LYS196.O 43.60%
TYR36.N-PHE57.O 44.20%
GLY53.N-LYS7.O 43.60%
SER104.N-PRO97.O 43.20%
LEU260.N-PHE305.O 43.40%
ARG66.N-ASP62.O 44.00%
THR91.N-ALA87.O 43.60%
ASP287.N-HIS290.O 42.80%
VAL99.N-LEU102.O 42.40%
ASP287.N-HIS290.O 43.40%
GLN238.NE2-SER240.OG 42.80%
GLY53.N-LYS7.O 42.60%
LEU186.N-THR198.O 42.20%
VAL221.N-GLN233.O 43.40%
ALA136.N-ALA132.O 42.80%
THR171.OG1-ARG167.O 42.60%
ASN111.ND2-LYS106.O 42.20%
ILE277.N-ALA262.O 43.20%
TYR73.N-ALA69.O 41.40%
THR169.OG1-ASP165.O 42.20%
LEU151.N-ASN147.O 41.00%
TYR306.OH-LEU212.O 43.20%
MET24.N-LYS4.O 41.40%
PHE70.N-ARG66.O 41.80%
GLN233.N-VAL221.O 41.00%
VAL188.N-LYS196.O 43.20%
THR35.N-THR43.OG1 41.00%
MET24.N-LYS4.O 41.60%
ILE223.N-ALA231.O 40.60%
THR35.N-THR43.OG1 43.20%
GLY210.N-SER246.O 40.20%
ILE223.N-ALA231.O 41.00%
GLY53.N-LYS7.O 40.60%
VAL304.N-MET245.O 43.00%
ASN129.N-HIS176.O 40.20%
GLN233.N-VAL221.O 40.80%
TYR73.N-ALA69.O 40.40%
LEU37.N-ALA40.O 42.60%
THR103.N-GLN122.OE1 40.00%
THR11.OG1-ASN16.O 40.40%
THR103.N-GLN122.OE1 40.40%
LEU121.N-VAL117.O 42.40%
TYR155.OH-TYR73.O 39.60%
VAL221.N-GLN233.O 40.00%
THR11.OG1-ASN16.O 40.40%
ASN129.N-HIS176.O 42.40%
VAL185.N-GLN237.O 39.40%
TYR137.N-LEU133.O 40.00%
PHE57.N-TYR36.O 40.00%
GLN233.N-VAL221.O 42.20%
ASN178.N-LYS127.O 39.40%
THR278.N-TYR284.O 40.00%
THR91.N-ALA87.O 39.80%
VAL185.N-GLN237.O 42.00%
THR11.OG1-ASN16.O 39.40%
GLU239.N-LYS183.O 40.00%
THR171.OG1-ARG167.O 39.60%
LEU260.N-PHE305.O 42.00%
PHE70.N-ARG66.O 39.20%
THR198.N-LEU186.O 39.60%
GLU135.N-PRO131.O 39.00%
ASN16.N-ASP13.OD1 41.60%
TYR36.N-PHE57.O 38.40%
LEU151.N-ASN147.O 39.40%
(continued)
14.4 Concluding Remarks
451
Table 14.3 (continued) Model1-optimized
Model2-optimized
Model3-optimized
Model4-optimized
LEU37.N-ALA40.O 38.60%
THR11.OG1-ASN16.O 41.60%
VAL188.N-LYS196.O 38.40%
TYR306.OH-LEU212.O 39.20%
LEU173.N-THR169.O 38.60%
LYS307.N-THR258.O 41.60%
ARG66.N-ASP62.O 38.00%
LEU37.N-ALA40.O 39.00%
THR198.N-LEU186.O 37.80%
LEU186.N-THR198.O 41.20%
THR103.OG1-ALA140.O 37.80%
ARG66.N-ASP62.O 38.80%
THR278.N-TYR284.O 37.40%
ILE223.N-ALA231.O 41.20%
ASN16.N-ASP13.OD1 37.60%
LEU173.N-THR169.O 38.40%
GLN122.NE2-THR103.O 37.40%
GLY53.N-LYS7.O 40.20%
GLY220.N-ASN216.O 37.20%
CYS149.N-ALA145.O 37.80%
MET207.N-VAL203.O 37.40%
PHE70.N-ARG66.O 39.40%
VAL221.N-GLN233.O 37.00%
TYR36.N-PHE57.O 37.60%
ASN129.N-HIS176.O 37.20%
TYR265.OH-ASN268.O 39.20%
GLN122.NE2-THR103.O 36.80%
MET207.N-VAL203.O 37.20%
THR35.N-THR43.OG1 37.00%
SER156.OG-ILE152.O 38.80%
LEU124.N-ALA120.O 36.60%
ARG141.N-TYR137.O 37.00%
TYR297.OH-GLU264.OE1 36.60%
TYR137.N-LEU133.O 38.20%
TYR297.OH-GLU264.OE1 36.20%
TYR73.N-ALA69.O 37.00%
ARG66.N-ASP62.O 36.20%
GLN238.NE2-SER240.OG 37.80%
GLN134.N-ALA130.O 36.00%
ASN111.ND2-LYS106.O 36.40%
SER246.OG-ASP303.OD1 36.00%
MET207.N-VAL203.O 37.80%
TYR306.OH-LEU212.O 36.00%
THR35.N-THR43.OG1 36.00%
ALA136.N-ALA132.O 36.00%
TYR265.N-PRO300.O 37.60%
GLU135.N-PRO131.O 35.80%
TYR297.OH-GLU264.OE2 36.00%
LYS307.N-THR258.O 35.80%
LEU173.N-THR169.O 36.60%
ASP23.N-GLN31.OE1 35.80%
VAL185.N-GLN237.O 36.00%
TYR36.N-PHE57.O 35.60%
CYS149.N-ALA145.O 35.40%
THR198.N-LEU186.O 35.60%
LEU186.N-THR198.O 35.80%
ILE152.N-PHE148.O 35.40%
GLY210.N-SER246.O 35.20%
SER86.N-GLY82.O 35.60%
SER156.OG-ILE152.O 35.40%
LYS280.N-THR282.O 35.40%
PHE9.N-LYS54.O 35.00%
TYR297.OH-GLU264.OE2 35.40%
HIS51.N-HIS48.O 35.20%
SER86.N-GLY82.O 34.60%
SER67.N-ASP63.O 35.00%
HIS51.N-HIS48.O 35.20%
SER67.N-ASP63.O 35.00%
THR275.N-GLU264.O 34.40%
TYR297.OH-GLU264.OE1 34.80%
SER156.OG-ILE152.O 35.00%
LEU81.N-ASP77.O 34.40%
GLN134.N-ALA130.O 34.40%
ASN111.ND2-LYS106.O 34.80%
VAL22.N-ILE6.O 35.00%
VAL22.N-ILE6.O 34.20%
GLY210.N-SER246.O 34.00%
ARG141.N-TYR137.O 34.60%
SER246.OG-ASP303.OD1 35.00%
SER86.N-GLY82.O 34.00%
ASN263.ND2-ASP303.OD2 33.60%
ASP23.N-GLN31.OE1 34.20%
PHE57.N-TYR36.O 34.80%
LYS307.N-THR258.O 34.00%
ASN16.N-ASP13.OD1 33.40%
THR292.N-ARG285.O 34.20%
ASN111.ND2-LYS106.O 34.80%
ASN16.N-ASP13.OD2 34.00%
PHE9.N-LYS54.O 33.40%
THR278.N-TYR284.O 33.60%
TYR234.N-ASN187.O 34.20%
THR292.N-ARG285.O 33.80%
TYR297.OH-GLU264.OE2 33.40%
THR10.N-HIS18.O 33.60%
THR10.N-HIS18.O 33.80%
ALA247.N-THR302.O 33.80%
HIS51.N-HIS48.O 33.00%
ALA247.N-THR302.O 33.40%
LEU151.N-ASN147.O 32.80%
ALA120.N-SER116.O 33.40%
VAL22.N-ILE6.O 32.40%
GLU239.N-LYS183.O 33.40%
TYR28.OH-HIS51.ND1 32.40%
LYS92.N-LEU88.O 33.40%
SER67.N-ASP63.O 31.80%
TYR28.OH-HIS51.ND1 33.20%
THR169.OG1-ASP165.O 32.20%
TYR297.OH-GLU264.OE1 33.20%
THR103.OG1-ALA140.O 31.80%
PHE57.N-TYR36.O 33.20%
LEU235.N-LEU217.O 32.00%
SER246.OG-ASP303.OD2 33.20%
THR10.N-HIS18.O 31.60%
ARG184.N-LEU200.O 32.60%
MET207.N-VAL203.O 32.00%
ASN178.N-LYS127.O 32.80%
ALA132.N-TYR72.O 31.60%
LYS92.N-LEU88.O 32.40%
ASN110.ND2-GLY161.O 31.60%
THR10.N-HIS18.O 32.80%
ARG184.N-LEU200.O 31.60%
VAL22.N-ILE6.O 32.20%
PHE9.N-LYS54.O 31.60%
GLY210.N-SER246.O 32.20%
ARG285.NE-GLU264.OE2 31.40%
SER246.OG-ASP303.OD2 31.60%
SER25.N-ASP23.OD2 31.20%
PHE9.N-LYS54.O 32.00%
GLU239.N-LYS183.O 31.40%
TYR73.N-ALA69.O 31.20%
CYS149.N-ALA145.O 30.80%
LEU124.N-ALA120.O 31.80%
LEU124.N-ALA120.O 31.40%
TYR297.OH-GLU264.OE2 31.20%
SER67.N-ASP63.O 30.80%
ASN16.N-ASP13.OD1 31.60%
SER156.N-ILE152.O 31.20%
LEU235.N-LEU217.O 30.80%
TYR137.N-LEU133.O 30.20%
GLN238.NE2-SER240.OG 31.20%
ASP23.N-GLN31.OE1 31.20%
ASN89.N-MET85.O 30.60%
ARG184.N-LEU200.O 30.20%
ARG184.N-LEU200.O 31.20%
LYS92.N-LEU88.O 30.80%
ASN263.ND2-ASP303.OD1 29.80%
LEU186.N-THR198.O 29.80%
LEU254.N-TYR297.O 31.00%
TYR28.OH-HIS51.ND1 30.20%
SER86.N-GLY82.O 29.60%
THR292.N-ARG285.O 29.80%
THR169.N-ASP165.O 30.60%
ALA247.N-THR302.O 30.20%
LYS280.N-THR282.O 29.40%
MET294.N-LEU283.O 29.60%
PHE57.N-TYR36.O 30.40%
ALA231.N-ILE223.O 30.00%
HIS51.N-HIS48.O 29.40%
SER156.N-ILE152.O 29.60%
TYR28.OH-HIS51.ND1 29.80%
452
14 PLpro Binding with 12 Compounds
Table 14.4 The HBs with more than 30% occupancy rates from the analyses of the 5 (for Model5optimized to Model7-optimized) or 2 (for Model8-optimized) .μs’ MD trajectory data of [321] Model5-optimized
Model6-optimized
Model7-optimized
Model8-optimized
THR302.N-ASN263.O 72.80%
PHE56.N-PHE9.O 66.80%
MET244.N-VAL206.O 72.40%
TYR155.N-LEU151.O 77.50%
TYR155.N-LEU151.O 70.40%
PHE305.N-CYS261.O 66.60%
LEU200.N-ARG184.O 70.20%
PHE56.N-PHE9.O 72.50%
ILE286.N-HIS276.O 68.20%
MET244.N-VAL206.O 65.20%
TYR155.N-LEU151.O 70.00%
LEU200.N-ARG184.O 70.50%
GLU264.N-THR275.O 67.80%
LEU200.N-ARG184.O 64.00%
ILE286.N-HIS276.O 69.20%
MET244.N-VAL206.O 69.00%
MET244.N-VAL206.O 67.40%
TYR155.N-LEU151.O 63.40%
PHE56.N-PHE9.O 63.80%
PHE305.N-CYS261.O 68.50%
ASN263.ND2-ASP303.OD2 67.20%
PHE32.N-TYR28.O 62.40%
ARG184.NE-GLN238.OE1 62.80%
TYR155.OH-TYR73.O 65.00%
LEU200.N-ARG184.O 65.80%
MET170.N-VAL166.O 61.00%
PHE32.N-TYR28.O 60.40%
LEU118.N-LEU114.O 64.00%
ASN263.N-ASP303.O 65.60%
MET245.N-VAL304.O 60.00%
LEU118.N-LEU114.O 59.20%
MET245.N-VAL304.O 64.00%
SER246.OG-ASP303.OD1 63.00%
VAL8.N-GLN20.O 58.20%
LEU174.N-MET170.O 58.80%
ILE286.N-HIS276.O 62.50%
TYR265.OH-ASN268.O 62.40%
ARG184.NE-GLN238.OE1 57.00%
TYR84.N-PHE80.O 58.40%
PHE32.N-TYR28.O 60.00%
LEU118.N-LEU114.O 62.00%
LYS106.N-LYS95.O 56.80%
GLN238.NE2-ALA205.O 57.80%
GLN238.NE2-ALA205.O 59.50%
PHE56.N-PHE9.O 61.00%
ILE286.N-HIS276.O 55.60%
MET245.N-VAL304.O 57.00%
TYR84.N-PHE80.O 59.50%
MET245.N-VAL304.O 60.80%
LEU118.N-LEU114.O 55.20%
THR35.OG1-GLY33.O 57.00%
SER246.OG-ASP303.OD1 59.50%
TYR84.OH-ASN147.OD1 60.20%
LEU121.N-VAL117.O 55.20%
TYR155.OH-TYR73.O 56.40%
MET170.N-VAL166.O 58.50%
TYR84.N-PHE80.O 60.00%
MET85.N-LEU81.O 54.80%
PHE305.N-CYS261.O 56.40%
VAL8.N-GLN20.O 57.50%
PHE305.N-CYS261.O 60.00%
TYR84.N-PHE80.O 54.40%
THR302.N-ASN263.O 55.80%
ARG184.NE-GLN238.OE1 57.00%
LYS106.N-LYS95.O 59.60%
GLN238.NE2-ALA205.O 53.80%
LYS106.N-LYS95.O 55.00%
LEU174.N-MET170.O 56.50%
MET170.N-VAL166.O 58.20%
THR35.OG1-GLY33.O 52.80%
MET170.N-VAL166.O 54.80%
TYR73.OH-VAL12.O 55.00%
THR302.OG1-ALA247.O 56.60%
SER104.N-PRO97.O 52.60%
GLU264.N-THR275.O 53.20%
PHE128.N-GLN134.OE1 54.50%
ASN187.N-TYR234.O 56.00%
THR302.N-ASN263.O 52.20%
MET85.N-LEU81.O 53.00%
GLN238.NE2-SER240.OG 54.00%
GLN238.NE2-ALA205.O 55.60%
GLN233.N-VAL221.O 52.00%
LEU119.N-SER115.O 52.40%
ALA140.N-ALA136.O 53.50%
PHE128.N-GLN134.OE1 55.20%
LEU88.N-TYR84.O 50.80%
ASN187.N-TYR234.O 52.40%
LYS106.N-LYS95.O 53.50%
PHE32.N-TYR28.O 55.00%
TYR284.N-THR278.O 50.60%
GLY220.N-ASN216.O 52.20%
VAL99.N-LEU102.O 52.50%
LEU174.N-MET170.O 54.40%
ILE223.N-ALA231.O 50.40%
VAL8.N-GLN20.O 52.00%
LEU119.N-SER115.O 52.50%
ALA140.N-ALA136.O 54.40%
PHE128.N-GLN134.OE1 50.20%
ARG141.N-TYR137.O 52.00%
ILE152.N-PHE148.O 52.50%
VAL8.N-GLN20.O 54.00%
ARG285.N-THR292.O 50.20%
LEU88.N-TYR84.O 51.80%
GLN233.N-VAL221.O 51.50%
ARG184.NE-GLN238.OE1 53.60%
LEU260.N-PHE305.O 50.00%
TYR265.N-PRO300.O 51.60%
TYR208.OH-GLN233.OE1 50.50%
VAL99.N-LEU102.O 53.40%
LEU119.N-SER115.O 50.00%
PHE128.N-GLN134.OE1 50.60%
VAL189.N-THR232.O 50.50%
THR103.N-GLN122.OE1 52.60%
GLN20.N-VAL8.O 48.80%
LEU121.N-VAL117.O 50.60%
GLN20.N-VAL8.O 49.50%
GLU135.N-PRO131.O 52.00%
GLU264.N-THR275.O 48.80%
THR169.OG1-ASP165.O 49.80%
MET85.N-LEU81.O 49.50%
LEU88.N-TYR84.O 51.80%
THR169.OG1-ASP165.O 48.40%
ASP287.N-HIS290.O 48.60%
ARG285.N-THR292.O 49.50%
MET85.N-LEU81.O 51.40%
ARG141.N-TYR137.O 48.20%
ILE277.N-ALA262.O 48.20%
LEU88.N-TYR84.O 49.50%
THR35.OG1-GLY33.O 51.00%
ALA140.N-ALA136.O 48.00%
VAL188.N-LYS196.O 47.80%
THR169.OG1-ASP165.O 49.00%
TYR265.N-PRO300.O 50.80%
LEU174.N-MET170.O 47.60%
ALA140.N-ALA136.O 47.80%
THR103.N-GLN122.OE1 48.50%
ILE152.N-PHE148.O 50.80%
TYR84.OH-ASN147.OD1 47.60%
TYR73.OH-VAL12.O 47.60%
ASN129.N-HIS176.O 48.50%
ASN16.N-ASP13.OD2 50.40%
VAL189.N-THR232.O 46.60%
MET24.N-LYS4.O 47.20%
ASN178.N-LYS127.O 48.50%
LEU119.N-SER115.O 49.60%
TYR208.OH-GLN233.OE1 46.40%
SER104.N-PRO97.O 46.60%
VAL304.N-MET245.O 48.00%
GLN20.N-VAL8.O 49.00%
GLN122.NE2-LEU118.O 45.60%
GLN122.NE2-LEU118.O 46.60%
GLY53.N-LYS7.O 47.50%
VAL188.N-LYS196.O 48.40%
LYS307.N-THR258.O 45.60%
VAL304.N-MET245.O 46.40%
LEU121.N-VAL117.O 47.50%
SER104.N-PRO97.O 48.20%
LEU37.N-ALA40.O 44.20%
TYR284.N-THR278.O 46.20%
GLU135.N-PRO131.O 47.00%
ASP287.N-HIS290.O 48.20%
MET24.N-LYS4.O 43.40%
GLN20.N-VAL8.O 45.00%
TYR265.N-PRO300.O 47.00%
GLY220.N-ASN216.O 47.80%
ASN187.N-TYR234.O 43.00%
THR103.N-GLN122.OE1 45.00%
GLN122.NE2-LEU118.O 46.50%
ILE277.N-ALA262.O 47.60%
VAL99.N-LEU102.O 42.60%
LEU37.N-ALA40.O 45.00%
LEU151.N-ASN147.O 46.50%
ASN178.N-LYS127.O 47.00%
ILE277.N-ALA262.O 42.60%
GLY53.N-LYS7.O 44.20%
TYR306.OH-LEU212.O 46.50%
THR169.OG1-ASP165.O 47.00%
GLN238.NE2-SER240.OG 42.60%
ILE223.N-ALA231.O 44.20%
TYR284.N-THR278.O 45.50%
TYR155.OH-TYR73.O 47.00%
PHE70.N-ARG66.O 42.40%
LEU260.N-PHE305.O 44.00%
ARG66.N-ASP62.O 45.00%
LEU37.N-ALA40.O 46.80%
GLY53.N-LYS7.O 42.20%
GLN238.NE2-SER240.OG 44.00%
ASP287.N-HIS290.O 45.00%
VAL304.N-MET245.O 46.20%
THR35.N-THR43.OG1 41.80%
TYR306.OH-LEU212.O 43.80%
THR302.N-ASN263.O 45.00%
ILE223.N-ALA231.O 45.80%
THR91.N-ALA87.O 41.80%
GLN233.N-VAL221.O 43.80%
GLU264.N-THR275.O 44.50%
TYR284.N-THR278.O 45.60%
TYR265.OH-ASN268.O 41.80%
ILE152.N-PHE148.O 43.40%
THR35.OG1-GLY33.O 44.50%
VAL189.N-THR232.O 45.60%
THR278.N-TYR284.O 41.60%
ASN263.N-ASP303.O 43.40%
LEU260.N-PHE305.O 44.50%
ALA132.N-TYR72.O 45.60%
TYR155.OH-TYR73.O 41.60%
ASN178.N-LYS127.O 42.20%
ARG141.N-TYR137.O 44.00%
MET24.N-LYS4.O 45.20%
TYR306.OH-LEU212.O 41.40%
TYR73.N-ALA69.O 41.80%
ILE223.N-ALA231.O 44.00%
LEU121.N-VAL117.O 45.20%
TYR265.N-PRO300.O 41.40%
VAL189.N-THR232.O 41.40%
MET24.N-LYS4.O 43.50%
GLN122.NE2-LEU118.O 45.00%
TYR73.OH-VAL12.O 41.20%
LEU151.N-ASN147.O 40.80%
ALA247.N-THR302.O 43.00%
SER116.OG-ASN263.OD1 44.80%
TYR297.OH-GLU264.OE2 41.20%
VAL185.N-GLN237.O 40.40%
LEU37.N-ALA40.O 42.50%
ARG285.N-THR292.O 44.80%
ASP287.N-HIS290.O 40.80%
THR278.N-TYR284.O 40.20%
THR302.OG1-ASP303.OD2 42.50%
LEU260.N-PHE305.O 44.40%
ASN129.N-HIS176.O 40.80%
ASN129.N-HIS176.O 40.00%
SER104.N-PRO97.O 42.50%
VAL185.N-GLN237.O 42.80%
TYR73.N-ALA69.O 40.60%
THR91.N-ALA87.O 39.80%
ALA231.N-ILE223.O 42.50%
GLN233.N-VAL221.O 42.60%
VAL185.N-GLN237.O 40.40%
VAL99.N-LEU102.O 39.40%
TYR265.OH-ASN268.O 42.00%
ASN129.N-HIS176.O 42.60%
THR103.N-GLN122.OE1 40.00%
THR11.OG1-ASN16.O 39.00%
ILE277.N-ALA262.O 42.00%
THR198.N-LEU186.O 42.40%
THR11.OG1-ASN16.O 40.00%
ARG285.N-THR292.O 38.40%
ASN111.N-ALA108.O 41.50%
THR35.N-THR43.OG1 42.40%
TYR36.N-PHE57.O 39.60%
LEU173.N-THR169.O 38.20%
VAL185.N-GLN237.O 40.50%
TYR306.OH-LEU212.O 42.40%
THR103.OG1-ALA140.O 39.00%
TYR36.N-PHE57.O 38.20%
THR278.N-TYR284.O 40.00%
(continued)
14.4 Concluding Remarks
453
Table 14.4 (continued) Model5-optimized
Model6-optimized
Model7-optimized
Model8-optimized
GLN122.NE2-THR103.O 42.40%
LYS280.N-THR282.O 38.80%
THR198.N-LEU186.O 38.00%
ASN187.N-TYR234.O 40.00%
THR171.OG1-ARG167.O 42.20%
VAL304.N-MET245.O 38.60%
GLU135.N-PRO131.O 37.40%
SER86.N-GLY82.O 40.00%
THR169.N-ASP165.O 41.60%
MET207.N-VAL203.O 38.20%
ARG66.N-ASP62.O 37.40%
ALA120.N-SER116.O 39.50%
THR91.N-ALA87.O 41.40%
GLU135.N-PRO131.O 38.00%
TYR297.OH-GLU264.OE1 37.00%
TYR137.N-LEU133.O 39.00%
LEU151.N-ASN147.O 41.40%
GLY220.N-ASN216.O 38.00%
VAL221.N-GLN233.O 37.00%
TYR234.N-ASN187.O 39.00%
ARG141.N-TYR137.O 40.20%
ASP23.N-GLN31.OE1 37.80%
PHE57.N-TYR36.O 36.60%
GLN122.NE2-THR103.O 38.50%
ALA120.N-SER116.O 40.20%
THR198.N-LEU186.O 37.80%
THR35.N-THR43.OG1 36.60%
LYS92.N-LEU88.O 38.50%
LEU173.N-THR169.O 40.00%
TYR234.N-ASN187.O 37.60%
SER86.N-GLY82.O 36.60%
TYR73.N-ALA69.O 38.00%
GLN238.NE2-SER240.OG 39.60%
VAL188.N-LYS196.O 37.40%
SER116.OG-ASN263.OD1 36.20%
GLY210.N-SER246.O 37.50%
ARG66.N-ASP62.O 38.60%
GLY210.N-SER246.O 37.40%
PHE70.N-ARG66.O 35.60%
THR11.OG1-ASN16.O 37.50%
SER156.OG-ILE152.O 38.60%
ALA136.N-ALA132.O 37.40%
GLN122.NE2-THR103.O 35.60%
ASP23.N-GLN31.OE1 37.50%
THR278.N-TYR284.O 38.00%
GLN134.N-ALA130.O 37.20%
SER67.N-ASP63.O 35.60%
THR10.N-HIS18.O 37.50%
GLY210.N-SER246.O 38.00%
ARG66.N-ASP62.O 37.20%
TYR297.OH-GLU264.OE2 35.40%
THR171.OG1-ARG167.O 37.00%
VAL221.N-GLN233.O 37.80%
LEU151.N-ASN147.O 36.40%
PHE9.N-LYS54.O 35.20%
SER67.N-ASP63.O 36.50%
TYR36.N-PHE57.O 37.40%
ILE152.N-PHE148.O 36.40%
GLN134.N-ALA130.O 34.80%
GLU168.N-ASP165.OD2 36.00%
PHE57.N-TYR36.O 37.20%
THR10.N-HIS18.O 36.20%
LEU235.N-LEU217.O 34.60%
SER240.OG-GLU308.O 36.00%
TYR137.N-LEU133.O 37.20%
LEU186.N-THR198.O 36.20%
TYR84.OH-ASN147.OD1 34.60%
TYR36.N-PHE57.O 35.50%
LEU186.N-THR198.O 37.20%
GLN122.NE2-THR103.O 35.40%
LEU186.N-THR198.O 34.40%
SER156.OG-ILE152.O 35.50%
GLY53.N-LYS7.O 37.20%
VAL22.N-ILE6.O 35.20%
LYS92.N-LEU88.O 34.00%
THR35.N-THR43.OG1 35.50%
PHE70.N-ARG66.O 36.40%
SER67.N-ASP63.O 34.80%
VAL22.N-ILE6.O 33.80%
PHE70.N-ARG66.O 35.50%
LYS92.N-LEU88.O 35.80%
THR171.OG1-ARG167.O 34.20%
GLY210.N-SER246.O 33.80%
ASN263.ND2-ASP303.OD2 35.50%
THR11.OG1-ASN16.O 35.60%
VAL221.N-GLN233.O 34.20%
ASN89.N-MET85.O 33.40%
GLY220.N-ASN216.O 35.00%
TYR252.N-GLY299.O 34.60%
ASN178.N-LYS127.O 33.40%
SER246.OG-ASP303.OD1 33.20%
ASN111.ND2-LYS106.O 35.00%
THR10.N-HIS18.O 34.00%
HIS51.N-HIS48.O 33.20%
CYS149.N-ALA145.O 33.20%
CYS149.N-ALA145.O 35.00%
LEU124.N-ALA120.O 34.00%
ALA231.N-ILE223.O 33.00%
HIS51.N-HIS48.O 33.00%
TYR28.OH-HIS51.ND1 34.50%
LEU235.N-LEU217.O 33.80%
ASN263.N-ASP303.O 32.80%
ALA132.N-TYR72.O 32.20%
MET207.N-VAL203.O 34.50%
ASP23.N-GLN31.OE1 33.80%
TYR28.OH-HIS51.ND1 32.80%
ASN263.ND2-ASP303.OD2 32.00%
VAL221.N-GLN233.O 34.00%
CYS149.N-ALA145.O 33.40%
ALA132.N-TYR72.O 32.80%
ASN16.N-ASP13.OD2 32.00%
THR198.N-LEU186.O 34.00%
TYR73.N-ALA69.O 33.20%
LEU173.N-THR169.O 32.40%
HIS18.N-THR10.O 31.80%
PHE57.N-TYR36.O 34.00%
TYR297.OH-GLU264.OE1 33.00%
ASN16.N-ASP13.OD2 32.40%
TYR137.N-LEU133.O 31.80%
ARG184.N-LEU200.O 33.50%
VAL22.N-ILE6.O 33.00%
ARG285.NH2-GLU264.OE1 32.00%
ARG184.N-LEU200.O 31.60%
LEU186.N-THR198.O 33.50%
HIS51.N-HIS48.O 32.40%
CYS149.N-ALA145.O 31.60%
THR103.OG1-ALA140.O 31.20%
TYR297.OH-GLU264.OE1 33.50%
TYR306.N-VAL243.O 32.00%
SER156.N-ILE152.O 31.60%
ASN111.ND2-LYS106.O 31.00%
TYR297.OH-GLU264.OE2 33.00%
ALA231.N-ILE223.O 31.80%
THR171.N-ARG167.O 30.60%
ASN16.N-ASP13.OD1 30.60%
LYS307.N-THR258.O 33.00%
SER86.N-GLY82.O 31.00%
ASN111.ND2-LYS106.O 30.60%
TYR306.N-VAL243.O 30.60%
LEU235.N-LEU217.O 32.50%
MET207.N-VAL203.O 30.80%
ALA154.N-ALA150.O 30.60%
THR171.OG1-ARG167.O 30.20%
ALA154.N-ALA150.O 32.50%
THR171.N-ARG167.O 30.80%
ASN89.N-MET85.O 30.40%
THR10.N-HIS18.O 30.20%
SER25.N-ASP23.OD2 32.50%
HIS18.N-THR10.O 30.20%
SER86.N-GLY82.O 30.40%
SER156.OG-ILE152.O 29.60%
VAL22.N-ILE6.O 32.00%
ARG184.N-LEU200.O 30.00%
ASN16.N-ASP13.OD1 30.20%
SER156.N-ILE152.O 29.40%
THR91.OG1-ALA146.O 32.00%
PHE9.N-LYS54.O 30.00%
ALA247.N-THR302.O 30.00%
VAL243.N-TYR306.O 29.40%
ASN16.N-ASP13.OD2 31.50%
GLU239.N-LYS183.O 30.00%
TYR297.OH-GLU264.OE1 30.00%
ALA136.N-ALA132.O 29.20%
MET294.N-LEU283.O 31.00%
ASN16.ND2-ASP13.OD1 29.80%
LEU124.N-ALA120.O 29.80%
LYS307.N-THR258.O 29.20%
THR292.N-ARG285.O 30.50%
THR275.N-GLU264.O 29.80%
PHE9.N-LYS54.O 29.00%
THR91.OG1-ALA146.O 29.00%
GLU168.N-ASP165.OD1 30.50%
TYR297.OH-GLU264.OE2 29.60%
GLU239.N-LYS183.O 29.00%
MET207.N-VAL203.O 29.00%
SER104.OG-GLY288.O 30.50%
ASN89.N-MET85.O 29.60%
ARG184.N-LEU200.O 29.00%
TYR28.OH-HIS51.ND1 28.80%
LYS158.N-LEU153.O 30.00%
ARG285.NE-GLU264.OE2 29.20%
SER25.N-ASP23.OD1 29.00%
ARG285.NE-GLU264.OE1 28.80%
LYS183.N-GLU239.O 30.00%
454
14 PLpro Binding with 12 Compounds
Table 14.5 The HBs with more than 30% occupancy rates from the analyses of the 2 .μs’ MD trajectory data of [321] Model9-optimized
Model10-optimized
Model11-optimized
Model12-optimized
TYR84.N-PHE80.O 70.00%
TYR155.N-LEU151.O 71.50%
LEU118.N-LEU114.O 70.50%
LEU200.N-ARG184.O 68.50%
LEU200.N-ARG184.O 69.00%
PHE56.N-PHE9.O 71.00%
LEU200.N-ARG184.O 68.50%
TYR84.N-PHE80.O 68.50%
TYR155.N-LEU151.O 67.00%
MET245.N-VAL304.O 69.50%
MET244.N-VAL206.O 68.00%
TYR155.N-LEU151.O 67.50%
MET244.N-VAL206.O 66.00%
PHE305.N-CYS261.O 68.00%
MET245.N-VAL304.O 68.00%
MET245.N-VAL304.O 66.00%
MET245.N-VAL304.O 65.00%
TYR265.OH-ASN268.O 68.00%
PHE32.N-TYR28.O 66.00%
PHE56.N-PHE9.O 65.00%
LYS106.N-LYS95.O 64.50%
LEU118.N-LEU114.O 65.00%
ILE286.N-HIS276.O 66.00%
TYR84.OH-ASN147.OD1 63.50%
TYR73.OH-VAL12.O 62.50%
MET170.N-VAL166.O 65.00%
ARG184.NE-GLN238.OE1 64.00%
MET244.N-VAL206.O 62.50%
LEU174.N-MET170.O 62.50%
MET244.N-VAL206.O 64.00%
MET170.N-VAL166.O 63.50%
ILE286.N-HIS276.O 62.00%
ILE286.N-HIS276.O 62.00%
PHE32.N-TYR28.O 63.00%
THR302.N-ASN263.O 63.50%
LEU118.N-LEU114.O 61.00%
TYR84.OH-ASN147.OD1 62.00%
LEU200.N-ARG184.O 62.00%
TYR155.N-LEU151.O 62.50%
GLN238.NE2-ALA205.O 60.50%
PHE56.N-PHE9.O 59.00%
LYS106.N-LYS95.O 62.00%
PHE56.N-PHE9.O 61.00%
PHE32.N-TYR28.O 60.50%
ARG184.NE-GLN238.OE1 58.50%
ALA140.N-ALA136.O 59.50%
PHE305.N-CYS261.O 61.00%
LYS106.N-LYS95.O 60.00%
VAL8.N-GLN20.O 58.00%
ILE286.N-HIS276.O 59.00%
LEU121.N-VAL117.O 58.00%
THR103.N-GLN122.OE1 59.50%
LEU119.N-SER115.O 57.00%
VAL8.N-GLN20.O 57.50%
LYS106.N-LYS95.O 58.00%
TYR265.OH-ASN268.O 59.50%
PHE305.N-CYS261.O 57.00%
LYS307.N-THR258.O 57.00%
TYR155.OH-TYR73.O 56.50%
VAL8.N-GLN20.O 59.00%
PHE32.N-TYR28.O 56.00%
ARG184.NE-GLN238.OE1 56.50%
THR35.OG1-GLY33.O 55.00%
ASN16.N-ASP13.OD1 58.00%
LEU121.N-VAL117.O 55.50%
LEU119.N-SER115.O 56.00%
ASN263.N-ASP303.O 54.50%
LEU88.N-TYR84.O 57.00%
ASN178.N-LYS127.O 55.00%
GLN238.NE2-ALA205.O 56.00%
THR169.OG1-ASP165.O 54.00%
ALA140.N-ALA136.O 57.00%
THR169.OG1-ASP165.O 53.50%
PHE128.N-GLN134.OE1 55.50%
TYR73.OH-VAL12.O 53.00%
MET170.N-VAL166.O 56.50%
LYS307.N-THR258.O 53.50%
SER246.OG-ASP303.OD1 55.50%
TYR84.N-PHE80.O 52.50%
LEU119.N-SER115.O 55.00%
MET170.N-VAL166.O 53.50%
TYR84.N-PHE80.O 54.00%
ARG285.N-THR292.O 52.00%
ARG184.NE-GLN238.OE1 54.50%
THR35.OG1-GLY33.O 52.50%
TYR73.OH-VAL12.O 54.00%
LEU88.N-TYR84.O 51.50%
THR302.N-ASN263.O 54.00%
ARG141.N-TYR137.O 52.50%
TYR155.OH-TYR73.O 53.50%
VAL189.N-THR232.O 51.50%
LEU174.N-MET170.O 53.50%
GLN233.N-VAL221.O 52.00%
LEU174.N-MET170.O 53.00%
MET85.N-LEU81.O 51.00%
GLU264.N-THR275.O 53.50%
PHE128.N-GLN134.OE1 51.50%
THR35.OG1-GLY33.O 53.00%
GLN233.N-VAL221.O 51.00%
VAL304.N-MET245.O 53.50%
ILE223.N-ALA231.O 51.00%
ARG285.N-THR292.O 52.00%
GLN238.NE2-ALA205.O 50.50%
MET85.N-LEU81.O 53.00%
TYR208.OH-GLN233.OE1 51.00%
THR103.N-GLN122.OE1 51.50%
VAL8.N-GLN20.O 49.50%
PHE128.N-GLN134.OE1 53.00%
TYR284.N-THR278.O 50.50%
ASN187.N-TYR234.O 51.50%
THR103.N-GLN122.OE1 49.50%
PHE305.N-CYS261.O 52.00%
GLN238.NE2-ALA205.O 50.50%
VAL99.N-LEU102.O 50.50%
ILE152.N-PHE148.O 49.50%
TYR284.N-THR278.O 50.50%
LEU118.N-LEU114.O 50.50%
MET85.N-LEU81.O 50.00%
PHE70.N-ARG66.O 49.00%
ASN187.N-TYR234.O 50.00%
MET85.N-LEU81.O 50.50%
LEU260.N-PHE305.O 50.00%
LEU119.N-SER115.O 48.50%
GLN233.N-VAL221.O 49.00%
TYR155.OH-TYR73.O 50.00%
TYR284.N-THR278.O 49.50%
MET24.N-LYS4.O 48.00%
LEU260.N-PHE305.O 49.00%
THR302.N-ASN263.O 49.00%
GLN122.NE2-LEU118.O 49.00%
ILE277.N-ALA262.O 48.00%
THR35.OG1-GLY33.O 48.00%
THR103.N-GLN122.OE1 48.50%
LEU151.N-ASN147.O 48.50%
ASP287.N-HIS290.O 47.00%
GLY220.N-ASN216.O 48.00%
ILE152.N-PHE148.O 48.50%
VAL185.N-GLN237.O 47.50%
LEU174.N-MET170.O 46.50%
TYR155.OH-TYR73.O 48.00%
VAL304.N-MET245.O 48.50%
GLU264.N-THR275.O 47.50%
TYR284.N-THR278.O 46.50%
ASN263.N-ASP303.O 48.00%
LEU88.N-TYR84.O 48.50%
GLN20.N-VAL8.O 47.50%
ASN129.N-HIS176.O 46.00%
VAL185.N-GLN237.O 48.00%
ASN187.N-TYR234.O 48.00%
ILE152.N-PHE148.O 47.50%
GLU264.N-THR275.O 45.50%
ASN129.N-HIS176.O 47.50%
ARG285.N-THR292.O 47.50%
SER104.N-PRO97.O 47.00%
SER104.N-PRO97.O 45.00%
SER104.N-PRO97.O 47.00%
GLN20.N-VAL8.O 47.00%
LEU88.N-TYR84.O 47.00%
GLN20.N-VAL8.O 45.00%
LYS307.N-THR258.O 47.00%
VAL99.N-LEU102.O 46.50%
VAL188.N-LYS196.O 47.00%
ARG141.N-TYR137.O 44.50%
THR169.OG1-ASP165.O 46.50%
ALA140.N-ALA136.O 45.50%
THR302.N-ASN263.O 46.00%
PHE128.N-GLN134.OE1 44.00%
LEU121.N-VAL117.O 46.50%
SER104.N-PRO97.O 45.50%
TYR265.N-PRO300.O 46.00%
LEU173.N-THR169.O 44.00%
GLN20.N-VAL8.O 46.00%
GLN238.NE2-SER240.OG 45.50%
VAL304.N-MET245.O 46.00%
TYR73.N-ALA69.O 43.00%
VAL188.N-LYS196.O 45.00%
ILE277.N-ALA262.O 45.00%
VAL189.N-THR232.O 45.50%
VAL185.N-GLN237.O 43.00%
ARG141.N-TYR137.O 45.00%
MET24.N-LYS4.O 44.50%
GLU135.N-PRO131.O 45.50%
TYR306.OH-LEU212.O 43.00%
GLN122.NE2-LEU118.O 45.00%
VAL185.N-GLN237.O 44.50%
ASN129.N-HIS176.O 45.00%
GLN122.NE2-LEU118.O 43.00%
GLN238.NE2-SER240.OG 45.00%
GLY53.N-LYS7.O 43.50%
ILE223.N-ALA231.O 44.00%
THR278.N-TYR284.O 43.00%
ARG285.N-THR292.O 44.00%
VAL189.N-THR232.O 43.50%
MET24.N-LYS4.O 44.00%
LEU260.N-PHE305.O 42.50%
ASP287.N-HIS290.O 43.50%
LEU37.N-ALA40.O 43.50%
ASN111.ND2-LYS106.O 44.00%
TYR234.N-ASN187.O 42.50%
LEU151.N-ASN147.O 43.00%
THR91.N-ALA87.O 43.50%
THR171.OG1-ARG167.O 43.50%
TYR265.N-PRO300.O 42.50%
ASN111.N-ALA108.O 43.00%
ASP287.N-HIS290.O 43.00%
TYR306.OH-LEU212.O 43.50%
VAL99.N-LEU102.O 42.50%
ILE223.N-ALA231.O 43.00%
GLU264.N-THR275.O 43.00%
PHE57.N-TYR36.O 43.00%
VAL304.N-MET245.O 42.50%
VAL189.N-THR232.O 41.00%
GLN122.NE2-LEU118.O 43.00%
GLY220.N-ASN216.O 43.00%
PHE57.N-TYR36.O 42.50%
GLN122.NE2-THR103.O 41.00%
TYR234.N-ASN187.O 42.50%
THR278.N-TYR284.O 42.00%
TYR84.OH-ASN147.OD1 42.50%
THR35.N-THR43.OG1 41.00%
TYR73.N-ALA69.O 42.50%
ASN16.N-ASP13.OD2 42.00%
ASN16.N-ASP13.OD1 42.00%
VAL221.N-GLN233.O 41.00%
TYR36.N-PHE57.O 42.50%
GLY53.N-LYS7.O 41.50%
ALA140.N-ALA136.O 42.00%
THR171.OG1-ARG167.O 40.50%
LEU260.N-PHE305.O 42.50%
ILE277.N-ALA262.O 41.50%
LEU37.N-ALA40.O 42.00%
VAL99.N-LEU102.O 40.50%
THR11.OG1-ASN16.O 42.00%
GLN233.N-VAL221.O 41.50%
THR35.N-THR43.OG1 41.50%
MET24.N-LYS4.O 39.50%
ALA136.N-ALA132.O 40.50%
ASP287.N-HIS290.O 41.00%
GLY220.N-ASN216.O 41.00%
TYR265.N-PRO300.O 39.50%
SER86.N-GLY82.O 40.00%
THR169.OG1-ASP165.O 41.00%
ALA132.N-TYR72.O 41.00%
TYR73.N-ALA69.O 39.00%
ASN129.N-HIS176.O 39.50%
GLN122.NE2-THR103.O 40.50%
LEU151.N-ASN147.O 41.00%
TYR36.N-PHE57.O 38.50%
PHE57.N-TYR36.O 39.50%
THR198.N-LEU186.O 40.50%
TYR265.OH-ASN268.O 41.00%
MET207.N-VAL203.O 38.50%
ASP23.N-GLN31.OE1 39.00%
VAL221.N-GLN233.O 40.50%
ILE223.N-ALA231.O 40.50%
LEU186.N-THR198.O 38.50%
(continued)
14.4 Concluding Remarks
455
Table 14.5 (continued) Model9-optimized
Model10-optimized
Model11-optimized
Model12-optimized
ARG184.N-LEU200.O 38.50%
LEU121.N-VAL117.O 40.00%
GLU135.N-PRO131.O 40.00%
THR91.N-ALA87.O 38.50%
VAL188.N-LYS196.O 38.00%
THR11.OG1-ASN16.O 39.50%
SER86.N-GLY82.O 40.00%
ILE152.N-PHE148.O 38.00%
ARG66.N-ASP62.O 37.50%
THR35.N-THR43.OG1 39.00%
THR10.N-HIS18.O 40.00%
THR198.N-LEU186.O 38.00%
LYS280.N-THR282.O 37.50%
TYR36.N-PHE57.O 39.00%
VAL221.N-GLN233.O 39.50%
LYS92.N-LEU88.O 37.50%
THR278.N-TYR284.O 37.50%
LEU37.N-ALA40.O 39.00%
THR91.N-ALA87.O 39.50%
LEU37.N-ALA40.O 36.00%
SER246.OG-ASP303.OD2 37.50%
LEU173.N-THR169.O 39.00%
THR198.N-LEU186.O 39.00%
ASN111.ND2-LYS106.O 35.50%
THR198.N-LEU186.O 37.00%
ARG141.N-TYR137.O 38.50%
SER246.OG-ASP303.OD2 39.00%
THR169.N-ASP165.O 35.50%
TYR297.OH-GLU264.OE1 36.50%
ARG66.N-ASP62.O 38.00%
GLN122.NE2-THR103.O 38.50%
ARG285.NE-GLU264.OE1 35.50%
VAL221.N-GLN233.O 36.50%
ALA120.N-SER116.O 38.00%
GLY210.N-SER246.O 38.00%
ASP23.N-GLN31.OE1 35.00%
TYR297.OH-GLU264.OE2 36.50%
MET207.N-VAL203.O 38.00%
GLY53.N-LYS7.O 38.00%
ARG184.N-LEU200.O 35.00%
GLY210.N-SER246.O 36.50%
SER156.OG-ILE152.O 38.00%
GLN238.NE2-SER240.OG 37.50%
THR11.OG1-ASN16.O 34.50%
HIS51.N-HIS48.O 35.50%
GLN238.NE2-SER240.OG 38.00%
GLN134.N-ALA130.O 37.50%
GLU135.N-PRO131.O 34.50%
ASN111.N-ALA108.O 35.50%
ALA247.N-THR302.O 37.50%
ASN263.ND2-ASP303.OD1 37.50%
ILE277.N-ALA262.O 34.50%
TYR265.N-PRO300.O 35.50%
TYR297.OH-GLU264.OE1 37.50%
LYS92.N-LEU88.O 37.00%
GLY210.N-SER246.O 34.50%
MET207.N-VAL203.O 35.00%
TYR84.OH-ASN147.OD1 37.50%
ARG66.N-ASP62.O 36.50%
ASN16.ND2-ASP13.OD2 34.50%
VAL22.N-ILE6.O 34.50%
ASN178.N-LYS127.O 36.50%
THR91.OG1-ALA146.O 36.50%
ARG66.N-ASP62.O 34.00%
TYR137.N-LEU133.O 34.50%
TYR73.N-ALA69.O 36.00%
THR275.N-GLU264.O 36.50%
THR91.OG1-ALA146.O 34.00%
THR35.N-THR43.OG1 34.50%
THR91.N-ALA87.O 36.00%
TYR297.OH-GLU264.OE1 36.50%
SER156.N-ILE152.O 34.00%
GLN122.NE2-THR103.O 34.50%
ARG184.N-LEU200.O 35.50%
TYR208.OH-GLN233.OE1 36.50%
HIS51.N-HIS48.O 34.00%
LYS158.N-LEU153.O 34.50%
SER86.N-GLY82.O 35.50%
SER67.N-ASP63.O 36.00%
TYR252.N-GLY299.O 34.00%
PHE70.N-ARG66.O 34.00%
ASP23.N-GLN31.OE1 35.50%
TYR36.N-PHE57.O 35.50%
CYS149.N-ALA145.O 33.50%
GLU168.N-ASP165.OD1 33.50%
LYS92.N-LEU88.O 35.00%
TYR297.OH-GLU264.OE2 35.00%
SER116.OG-ASN263.OD1 33.50%
THR10.N-HIS18.O 33.00%
ALA132.N-TYR72.O 35.00%
VAL22.N-ILE6.O 35.00%
ALA132.N-TYR72.O 33.00%
GLN134.N-ALA130.O 33.00%
ASN89.N-MET85.O 34.50%
LYS307.N-THR258.O 35.00%
TYR297.OH-GLU264.OE2 33.00%
GLU135.N-PRO131.O 33.00%
THR292.N-ARG285.O 34.50%
THR302.OG1-ALA247.O 35.00%
THR278.N-TYR284.O 33.00%
PHE9.N-LYS54.O 32.50%
PHE70.N-ARG66.O 34.50%
ASN187.N-TYR234.O 34.00%
SER246.OG-ASP303.OD1 33.00%
THR171.OG1-ARG167.O 32.50%
LEU186.N-THR198.O 34.00%
ASN111.ND2-LYS106.O 34.00%
VAL22.N-ILE6.O 33.00%
SER67.N-ASP63.O 32.00%
PHE9.N-LYS54.O 34.00%
HIS51.N-HIS48.O 33.50%
GLU239.N-LYS183.O 32.00%
TYR28.OH-HIS51.ND1 32.00%
TYR137.N-LEU133.O 33.50%
CYS149.N-ALA145.O 33.00%
PHE70.N-ARG66.O 32.00%
THR302.OG1-ASP303.OD1 32.00%
LEU124.N-ALA120.O 33.50%
MET207.N-VAL203.O 33.00%
TYR306.OH-LEU212.O 32.00%
ALA120.N-SER116.O 31.50%
SER67.N-ASP63.O 33.00%
LYS183.N-GLU239.O 33.00%
TYR297.OH-GLU264.OE1 32.00%
CYS149.N-ALA145.O 31.50%
TYR28.OH-HIS51.ND1 32.50%
ALA231.N-ILE223.O 32.50%
THR10.N-HIS18.O 32.00%
LEU186.N-THR198.O 31.50%
VAL22.N-ILE6.O 32.50%
VAL188.N-LYS196.O 32.50%
ARG83.NE-SER79.OG 32.00%
ARG83.NE-SER79.OG 31.50%
LYS280.N-THR282.O 32.00%
LEU186.N-THR198.O 32.50%
GLY53.N-LYS7.O 31.50%
SER156.OG-ILE152.O 31.50%
ARG285.NH2-GLU264.OE2 31.50%
ASP23.N-GLN31.OE1 32.00%
PHE9.N-LYS54.O 31.50%
ASN16.N-ASP13.OD2 31.00%
TYR252.N-GLY299.O 31.00%
TYR137.N-LEU133.O 32.00%
TYR28.OH-HIS51.ND1 31.00%
SER156.N-ILE152.O 31.00%
SER25.N-ASP23.OD1 30.50%
LYS158.NZ-LEU163.O 31.50%
ARG285.NH2-GLU264.OE2 31.00%
ALA231.N-ILE223.O 31.00%
ASN263.ND2-ASP303.OD2 30.50%
THR171.OG1-ARG167.O 31.00%
LEU254.N-TYR297.O 30.50%
LEU235.N-LEU217.O 31.00%
HIS51.N-HIS48.O 30.50%
GLU168.N-ASP165.OD2 30.50%
LEU173.N-THR169.O 30.50%
LEU173.N-THR169.O 30.50%
LEU235.N-LEU217.O 30.50%
THR292.N-ARG285.O 30.50%
SER156.OG-ILE152.O 30.50%
SER240.OG-GLU308.O 30.50%
TYR297.OH-GLU264.OE2 30.00%
TYR72.OH-GLU135.OE2 29.50%
ASN110.ND2-GLY161.O 30.50%
ASN89.N-MET85.O 30.50%
VAL42.N-THR35.O 30.00%
SER104.OG-GLY288.O 29.50%
ASN263.ND2-ASP303.OD2 30.00%
LEU151.N-ASN147.O 30.00%
THR10.N-HIS18.O 30.00%
SER25.N-ASP23.OD1 29.50%
SER67.N-ASP63.O 30.00%
LYS183.N-GLU239.O 30.00%
LYS183.N-GLU239.O 30.00%
MET294.N-LEU283.O 29.50%
TYR306.N-VAL243.O 29.50%
Chapter 15
3CLpro Binding with N3/Lopinavir/Ritonavir
Abstract This brief chapter is to do molecular dynamics (MD) studies on SARSCoV-2 3CLpro binding with three inhibitors N3, lopinavir, and ritonavir, respectively, and to do optimization studies on SARS-CoV-2 Mpro binding with top 100 compounds, respectively. Here, we present a note of results of studies: the catalytic dyad (HIS41 and CYS145) residues and the strong polar contact ARG40-ASP187 , etc. are always constructing a binding cavity for the inhibitors/compounds. SARSCoV-2 3CLpro is an attractive drug target against COVID-19; the note of structural bioinformatics presented by this brief chapter might be useful or helpful to drug designers. Keywords MD and optimization studies · SARS-CoV-2 3CLpro · 3CLpro-binding site · Top 100 compounds · Drug designing or discovery
15.1 Introduction SARS-CoV-2 3C-like protease (3CLpro) or called main protease (Mpro) is a key coronavirus enzyme (which plays a pivotal role in mediating viral replication and transcription) for the maturation of viral particles and an attractive drug target against COVID-19. In Sect. 2.3.2 of Chap. 2, we did MD studies on SARS-CoV2 3CLpro dimer (with unliganded active site/without ligand – we denoted as the 6Y84-dimer model and the 6LU7-dimer model ), without any binding. This chapter is doing MD and optimization studies on some bindings of SARS-CoV-2 3CLpro with inhibitors (such as N3, lopinavir, and ritonavir) and with top 100 drugs.
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 J. Zhang, Optimization-based Molecular Dynamics Studies of SARS-CoV-2 Molecular Structures, Springer Series in Biophysics 23, https://doi.org/10.1007/978-3-031-36773-1_15
457
458
15 3CLpro Binding with N3/Lopinavir/Ritonavir
15.2 Materials and Methods 15.2.1 N3 at the Binding Pocket of SARS-CoV-2 Mpro “Data includes all of the trajectories (1000) of classical all-atom MD simulations of inhibitor N3 at the binding pocket of SARS-CoV2 main protease target (PDB ID: 6LU7). In order to decrease the size of the file only protein and ligand trajectories were provided. Simulation has been performed with Desmond. Proteinligand complexes were obtained from RCSB PDB (PDB ID: 6LU7). Complex was placed in the cubic boxes with explicit TIP3P water models that have 10.0 Å thickness from surfaces of protein. The system is neutralized by adding counter ions, and salt solution of 0.15M NaCl was also used to adjust the concentration of the systems. The long-range electrostatic interactions were calculated by the particle mesh Ewald method. A cut-off radius of 9.0 Å was used for both van der Waals and Coulombic interactions. The temperature was set as 310 K initially, and NoseHoover thermostat was used for adjustment. Martyna-Tobias-Klein protocol was employed to control the pressure, which was set at 1.01325 bar. The time-step was assigned as 2.0 fs. The default values were used for minimization and equilibration steps, and finally 100 ns production run was performed for the simulations” [102] – we denote as the N3-model.
15.2.2 Lopinavir at the Binding Pocket of SARS-CoV-2 Mpro “Data includes all of the trajectories (2000) of classical all-atom MD simulations of Lopinavir at the binding pocket of SARS-CoV-2 main protease target. In order to decrease the size of the file, only protein and ligand trajectories were provided. Simulation has been performed with Desmond. Protein-ligand complexes were obtained by Glide/SP docking program. Complex was placed in the cubic boxes with explicit TIP3P water models that have 10.0 Å thickness from surfaces of protein. The system is neutralized by adding counter ions, and salt solution of 0.15M NaCl was also used to adjust the concentration of the systems. The long-range electrostatic interactions were calculated by the particle mesh Ewald method. A cut-off radius of 9.0 Å was used for both van der Waals and Coulombic interactions. The temperature was set as 310 K initially, and Nose-Hoover thermostat was used for adjustment. Martyna-Tobias-Klein protocol was employed to control the pressure, which was set at 1.01325 bar. The time-step was assigned as 2.0 fs. The default values were used for minimization and equilibration steps, and finally 500 ns production run was performed for the simulations” [103] – we denote as the Lopinavir-model.
15.2 Materials and Methods
459
15.2.3 Ritonavir at the Binding Pocket of SARS-CoV-2 Mpro “Data includes all of the trajectories (2000) of classical all-atom MD simulations of Ritonavir at the binding pocket of SARS-CoV2 main protease target. In order to decrease the size of the file only protein and ligand trajectories were provided. Simulation has been performed with Desmond. Protein-ligand complexes were obtained by Glide/SP docking program. Complex was placed in the cubic boxes with explicit TIP3P water models that have 10.0 Å thickness from surfaces of protein. The system is neutralized by adding counter ions, and salt solution of 0.15M NaCl was also used to adjust the concentration of the systems. The long-range electrostatic interactions were calculated by the particle mesh Ewald method. A cut-off radius of 9.0 Å was used for both van der Waals and Coulombic interactions. The temperature was set as 310 K initially, and Nose-Hoover thermostat was used for adjustment. Martyna-Tobias-Klein protocol was employed to control the pressure, which was set at 1.01325 bar. The time-step was assigned as 2.0 fs. The default values were used for minimization and equilibration steps, and finally 500 ns production run was performed for the simulation” [104] – we denote as the Ritonavir-model.
15.2.4 Top 100 Drugs Binding with SARS-CoV-2 Mpro “7922 compounds were downloaded from NPC database (https://tripod.nih.gov/ npc/). In order to eliminate the non-specific binders, some criteria including molecular weight, between 100–1000 g/mol; number of rotatable bonds, .