List of Figures
1 X-RAY CRYSTALLOGRAPHY 6
1.1. DIFFRACTION 8
1.2. THE DNA DOUBLE HELIX 13
1.3. SOLVING PROTEIN STRUCTURES 20
1.4. THE PHASE PROBLEM. 29
1.5. PROBLEM SET 35
2 NUCLEAR MAGNETIC RESONANCE 39
1.6. THE NMR PHENOMENON 39
1.7. CHEMICAL SHIFT. 41
1.8. J COUPLING 43
1.9. NUCLEAR OVERHAUSER EFFECT AND 2D NMR 45
1.10. PROBLEM SET 49
3 CRYO-ELECTRON MICROSCOPY 55
1.11. BACTERIORHODOPSIN 55
1.12. RADIATION DAMAGE 59
1.13. DIRECT ELECTRON DETECTORS AND VITRIFICATION. 60
1.14. COMPUTATIONAL ALGORITHMS 61
1.15. EXAMPLE - A BACTERIAL EFFLUX PUMP 63
1.16. PROBLEM SET 65
4 PROTEIN FOLDING 70
1.17. ANFINSENâS EXPERIMENTS 70
1.18. FREE ENERGY, ENTHALPY AND ENTROPY 72
1.19. HYDROPHOBIC EFFECT 80
1.20. LEVINTHAL PARADOX and FOLDING FUNNELS 82
1.21. PROBLEM SET 96
5 ARTIFICIAL INTELLIGENCE 101
1.22. SUPERVISED AND UNSUPERVISED LEARNING 101
1.23. DATA 103
1.24. FEATURES 107
1.25. CLASSICAL ML MODELS. 108
1.26. DEEP LEARNING 111
1.27. TRAINING THE MODEL 115
1.28. ML EXAMPLE â" T CELL RECEPTOR SPECIFICITY 116
1.29. BAYESIAN AI 121
1.30. ALPHAFOLD! 125
1.31. PROBLEM SET 131
6 MOLECULAR FORCES 3
6.1 QUANTUM MECHANICS 3
6.2 MOLECULAR MECHANICS FORCE FIELD 8
6.3 PROBLEM SET 19
7 VIBRATIONS AND CONFORMATIONAL TRANSITIONS 23
7.1 LOW-FREQUENCY VIBRATIONS 28
7.2 ANHARMONICITY AND CONFORMATIONAL TRANSITIONS 29
7.3 PROBLEM SET 33
8 MOLECULAR DYNAMICS SIMULATION 36
8.1 MD TRAJECTORIES. 36
8.2 INTERPRETATION OF MD 39
8.3 CONFORMATIONAL SUBSTATES AND ENERGY LANDSCAPES. 48
8.4 PROBLEM SET 50
9 EXPERIMENTS ON DYNAMICS 54
9.1 NMR 54
9.2 DYNAMIC NEUTRON SCATTERING 59
9.3 FLUORESCENCE SPECTROSCOPY 64
9.4 PROBLEM SETS 72
10 LIGAND BINDING. 76
10.1 LIGAND BINDING THERMODYNAMICS AND KINETICS. 76
10.2 WHAT MAKES A LIGAND BIND. 83
10.3 SOLVATION 91
10.4 KINETICS 97
10.5 PROBLEM SET 100
11 ALLOSTERY 105
11.1 HEMOGLOBIN 105
11.2 RAS AND THE ENSEMBLE MODEL. 114
11.3 G-PROTEIN COUPLED RECEPTORS 119
11.4 PROBLEM SET 125
12 INTRINSICALLY DISORDERED PROTEINS 129
12.1 SOLUTION SCATTERING 130
12.2 LIQUID-LIQUID PHASE SEPARATION AND BIOLOGICAL CONDENSATES 139
12.3 PROBLEM SET 143
13 ENZYME CATALYSIS 3
13.1 CHYMOTRYPSIN 4
13.2 PROTONATION STATES: MOTIONS OF PROTONS 12
13.3 PROBLEM SET 20
14 BIOLOGICAL MEMBRANES 25
14.1 PHASES AND DOMAINS 27
14.2 CHANNELS 36
14.3 PROBLEM SET 43
15 LIGHT-DRIVEN PROTEINS 48
15.1 PHOTOSYNTHESIS 48
15.2 RETINAL PROTEINS 65
15.3 VISION 69
15.5 PROBLEM SET 73
16 BIOLOGICAL COMPLEXES AND THE MACHINERY OF LIFE 78
16.1 THE RIBOSOME. 80
16.2 ATP SYNTHASE. 91
16.3 NUCLEAR PORE COMPLEX 96
16.4 SPLICEOSOME 100
16.5 PROBLEM SET 105
17. THE ENVIRONMENT 3
17.1 MERCURY 4
17.2 CIRCULAR BIOECONOMY 15
17.3 BIOENERGY 16
17.4 BIOBASED MATERIALS 39
17.5 SYNTHETIC BIOLOGY AND DE NOVO PROTEIN DESIGN 49
17.1 CLIMATE 59
17.2 PROBLEM SETS 63
18. HEALTH 69
18.1 STRUCTURE-BASED DRUG DISCOVERY 73
18.2 LEAD OPTIMIZATION 88
18.3 COVID 19. 94
18.4 MODULATING INTERACTIONS BETWEEN MACROMOLECULES 101
18.5 DRUG DISCOVERY - THE FUTURE 105
18.6 DESIGNING VACCINES 108
18.7 PROBLEM SETS 120
19. SOME CLOSING THOUGHTS 126
Index
