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. ANFINSEN'S 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 - 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.