Protein Folding Kinetics (eBook)

Preface 6
Preface to the first edition 7
Contents 9
Symbols 13
1 Introduction 14
2 Structures of proteins 18
2.1 Primary structure 18
2.2 Secondary structure 22
2.3 Tertiary structure 24
3 Physical interactions that determine the properties of proteins 30
3.1 Electrostatic interactions 30
3.2 Quantum-mechanical short-range repulsion 32
3.3 Hydrogen bonding 34
3.4 Hydrophobic interaction 35
4 Calculation of the kinetic rate constants 40
4.1 Transition state theory 41
4.2 Two-state transitions 42
4.3 Three-state transitions 44
4.4 Reversible sequential four-state transition 53
4.5 Reactions with monomer dimer transitions 54
4.6 Kinetic rate constants for perturbation methods 57
4.7 Summary 60
5 High kinetic resolution of protein folding events 64
5.1 Ultrafast mixing 64
5.2 Temperature-jump 68
5.3 Optical triggers 78
5.4 Acoustic relaxation 82
5.5 Pressure-jump 85
5.6 Dielectric relaxation and electric-field-jump 86
5.7 NMR line broadening 88
5.8 Summary 89
6 Kinetic methods for slow reactions 92
6.1 Stopped-flow nuclear magnetic resonance (NMR) 92
6.2 Fluorescence- and isotope-labeling 93
7 Resolution of protein structures in solution 96
7.1 Nuclear magnetic resonance 96
7.2 Circular dichroism 102
8 High structural resolution of transient protein conformations 108
8.1 NMR detection of H/D exchange kinetics 108
8.2 Time-resolved circular dichroism 111
8.3 F-value analysis 118
9 Experimental problems of the kinetic and structural resolution of reactions that involve proteins 138
9.1 Protein expression problems 138
9.2 Aggregation 142
9.3 Misfolding 146
9.4 Unstable curve fit 148
10 The folding pathway of a protein (barstar) at the resolution of individual residues from microseconds to seconds 150
10.1 Introduction 150
10.2 Materials and methods 151
10.3 Structure of native barstar 153
10.4 Residual structure in the cold-unfolded state 154
10.5 Gross features of the folding pathway of barstar 156
10.6 F-value analysis 162
10.7 Inter-residue contact maps 165
10.8 The highly resolved folding pathway of barstar 168
10.9 Structural disorder and misfolding 173
10.10 Structure of peptides of barstar 175
10.11 Nucleation condensation mechanism of folding 175
11 Highly resolved folding pathways and mechanisms of six proteins 178
11.1 General features of the main transition states for the formation of the native structures 178
11.2 Nucleation condensation 189
11.3 Framework-model-like properties 192
11.4 Conclusions 192
12 Structural determinants of the rate of protein folding 194
12.1 Chain topology as a major structural determinant of two- state folding 194
12.2 Chain topology of the transition state and implications for the mechanism of folding 197
12.3 Further factors 197
12.4 Ultrafast folding 198
13 Evolutionary computer programming of protein structure and folding 200
13.1 Evolution method 201
13.2 Protein folding and structure predictions 202
13.3 Further potential applications of the evolution method 207
14 Conclusions 208
References 210
Index 228