Non-covalent interactions in proteins 9781860947070, 1860947077

Table of contents :
Contents......Page 8
Preface......Page 12
1. Introduction......Page 14
1.1 Some Historical Notes......Page 17
1.2.1 The amino acids......Page 25
1.2.2 The polypeptide chain......Page 30
1.3 Non-covalent Interactions and Structure-Function Relationships in Proteins......Page 32
1.3.1 Some comments on Anfinsen's dogma......Page 33
1.3.2 Experimental measurements of non-covalent interactions in proteins......Page 34
References......Page 35
2. Van der Waals Interactions......Page 38
2.1 Observation of van der Waals Interactions......Page 39
2.2 Nature of van der Waals Interactions......Page 41
2.2.1 Dispersion forces......Page 42
2.2.2 Dipole-dipole interactions......Page 50
2.2.3 Dipole-induced dipole interactions......Page 55
2.2.4 Repulsive interactions......Page 57
2.3 Potential Functions for Application in Proteins......Page 59
2.4 Approximation for Polyatomic Systems......Page 61
References......Page 63
3.1 Nature of Hydrogen Bonds......Page 64
3.1.1 Proton donors electronegativity......Page 65
3.1.2 Proton acceptors......Page 68
3.2 Geometry and Strength of Hydrogen Bonds......Page 69
3.2.1 Directionality......Page 70
3.2.2 Hydrogen bond length......Page 77
3.2.3 Hydrogen bond strength......Page 80
3.2.4 Hydrogen bond potential functions......Page 84
3.3.1 Secondary structure elements......Page 86
3.3.2 Hydrogen bonds involving side chains......Page 89
3.3.3 Salt bridges......Page 91
3.3.4 Hydrogen bond networks......Page 93
3.4 Hydrogen Bonds and Protein Stability......Page 96
3.4.1 Hydrogen bonds within the polypeptide chain role in folding......Page 97
3.4.2 Hydrogen bonds involving side chain role in stability......Page 99
References......Page 102
4.1 Nature of Hydrophobic Interactions Pseudo Forces......Page 104
4.2.1 Flickering clusters model of water......Page 106
4.2.2 Hydrocarbons in water iceberg model......Page 109
4.3.1 Oil drop in water......Page 111
4.3.2 Experimental assessment of hydrophobic interaction......Page 113
4.4 Hydrophobic Interactions in Proteins......Page 115
4.4.1 Additivity of hydrophobic interactions......Page 117
4.4.2 Solvent accessibility......Page 118
4.4.3 Evaluation of hydrophobic interactions......Page 124
4.4.4 Size of the hydrophobic core......Page 129
4.4.5 Hydrophobic packing and packing defects......Page 134
References......Page 140
5. Electrostatic Interactions......Page 142
5.1.1 Poisson-Boltzmann equation......Page 143
5.1.2 Parameter of Debye......Page 148
5.1.3 The electrostatic potential of an ion in solution......Page 150
5.1.4 Extension for proteins......Page 152
5.2.1 Born model......Page 153
5.2.2 Application of the Born model for proteins: why do charges tend to be on protein surface?......Page 157
5.2.3 Generalised Born theory for proteins......Page 159
5.3.1 The protein molecule as a dielectric material......Page 164
5.3.2 Dielectric model for calculation of electrostatic interactions in proteins......Page 170
5.3.3 Numerical solution of the Poisson-Boltzmann equation finite difference method......Page 172
5.3.4 Boundary conditions......Page 181
5.3.5 Electrostatic potential calculated by means of the finite difference method......Page 184
References......Page 188
6. Ionisation Equilibria in Proteins......Page 190
6.1 Why Does One Need to Know Ionisation Equilibria?......Page 192
6.2.1 Protonation/deprotonation equilibria......Page 193
6.2.2 Henderson-Hasselbalch equation......Page 195
6.2.3 Degree of deprotonation and degree of protonation......Page 197
6.2.4 Ionisation equilibrium constants of model compounds......Page 199
6.3 Factors Determining Ionisation Equilibria in Proteins......Page 202
6.3.1.1 Born energy......Page 204
6.3.1.2 Calculation of the Born energy......Page 207
6.3.2 Interactions with the protein permanent charges......Page 210
6.3.3 Definition of intrinsic pK......Page 211
6.3.4 Charge-charge interactions......Page 212
6.4 Combinatorial Problem......Page 214
6.4.1 Solution based on the Boltzmann weighted sum......Page 215
6.4.2 Solution based on the Monte Carlo simulation......Page 219
6.5 Cooperative Ionisation......Page 222
References......Page 228
7.1 Allocation Variation of Polar Hydrogen Atoms......Page 230
7.1.1 Titratable and pH-sensitive sites......Page 231
7.1.2 Microscopic pK......Page 232
7.1.3 Population of the microscopic states......Page 237
7.2.1 Ionisation properties of Asp76 in ribonuclease T1......Page 242
7.2.2 Hydrogen bond rearrangement related to protein function......Page 247
7.3 Conformational Flexibility Involving Non-hydrogen Atoms......Page 252
7.3.1 Conformations generated by means of molecular dynamics simulation......Page 254
7.3.2 Average pK values......Page 259
7.3.3 Desolvation and charge-dipole energy compensation......Page 262
7.3.4 Dynamics of salt bridges......Page 265
References......Page 267
8.1 Definitions......Page 268
8.2 Unfolding Induced by pH......Page 270
8.3 Modelling of Unfolded Proteins......Page 275
8.3.1 Spherical model of unfolded proteins......Page 277
8.3.2 Size of the dielectric sphere......Page 278
8.3.3 Average distance between charges......Page 283
8.3.4 lonisation equilibria in unfolded proteins......Page 286
8.4 Thermal Stability of Proteins......Page 290
References......Page 294
Appendix A Basic Definitions of Thermodynamics and Statistical Thermodynamics......Page 296
Appendix B Electric Dipoles......Page 324
Appendix C Solution of Laplace and Poisson-Boltzmann Equation......Page 332
Index......Page 342