Hydration Structures of Proteins: Atomic Details

Description

This book describes hydration structures of proteins by combining experimental results with theoretical considerations. It is designed to introduce graduate students and researchers to microscopic views of the interactions between water and biological macromolecules and to provide them with an overview of the field. Topics on protein hydration from the past 25 years are examined, most of which involve crystallography, fluorescence measurements, and molecular dynamics simulations. In X-ray crystallography and molecular dynamics simulations, recent advances have accelerated the study of hydration structures over the entire surface of proteins. Experimentally, crystal structure analysis at cryogenic temperatures is advantageous in terms of visualizing the positions of hydration water molecules on the surfaces of proteins in their frozen-hydrated crystals. A set of massive data regarding hydration sites on protein surfaces provides an appropriate basis, enabling us to identify statistically significant trends in geometrical characteristics. Trajectories obtained from molecular dynamics simulations illustrate the motion of water molecules in the vicinity of protein surfaces at sufficiently high spatial and temporal resolution to study the influences of hydration on protein motion. Together with the results and implications of these studies, the physical principles of the measurement and simulation of protein hydration are briefly summarized at an undergraduate level. Further, the author presents recent results from statistical approaches to characterizing hydrogen-bond geometry in local hydration structures of proteins. The book equips readers to better understand the structures and modes of interaction at the interface between water and proteins. Referred to as “hydration structures”, they are the subject of much discussion, as they may help to answer the question of why water is indispensable for life at the molecular and atomic level. Preface Acknowledgements Contents About the Author Glossary of Symbols 1 Introduction 1.1 Water: The Cradle of Life 1.2 Structure and Interaction of Water Molecules 1.2.1 Structure of Water Molecules 1.2.2 Interactions Between Water Molecules 1.2.3 Hydrogen Bond Between Water Molecules 1.3 Phase Diagram of Water 1.3.1 Three Phases of Water 1.3.2 Hexagonal Ice and Amorphous Ice 1.4 Properties of Liquid Water 1.4.1 Unusual Physical Properties 1.4.2 Brownian Motion in Liquid Water 1.4.3 Structure of Liquid Water 1.5 Hydration 1.5.1 Solvation 1.5.2 Hydration 1.5.3 Hydration of Hydrophobic Molecules 1.6 Hydration Structures of Proteins 1.6.1 Proteins 1.6.2 Hydration Structures of Proteins 1.7 Scope of This Monograph References 2 Biophysical Methods to Investigate Hydration Structures of Proteins 2.1 Introduction 2.2 X-Ray Crystallography at Cryogenic Temperatures 2.2.1 Outline 2.2.2 Crystallographic Structure Refinement 2.2.3 Difference Fourier Map 2.2.4 X-Ray Crystallography at Cryogenic Temperatures 2.3 Cryogenic Electron Microscopy 2.3.1 Outline 2.3.2 Specimen Preparation and Image Collection 2.3.3 Image Processing and Single-Particle Analysis 2.4 Time-Resolved Fluorescence Measurement 2.4.1 Outline 2.4.2 Up-conversion Method 2.5 Molecular Dynamic Simulation 2.5.1 Outline 2.5.2 Force Field References 3 Hydration Structures Inside Proteins 3.1 Introduction 3.2 Water Molecules Inside Proteins 3.2.1 Tightly Bound Water Molecules 3.2.2 Water Molecules Confined Inside Proteins 3.3 Hydration Water Molecules as Glue in Protein Complexes 3.3.1 Hydration at the Subunit Interface of a Protein Complex 3.3.2 Hydration Sites Conserved in Protein Families 3.4 Hydration Water Molecules as Lubricant at the Protein Interface 3.5 Hydration Water Molecules in the Ligand-Binding Sites References 4 Hydration Layer Around Proteins 4.1 Introduction 4.2 Hydration Layer 4.2.1 First- and Second-Layer Classes 4.2.2 Distance Distribution and Positional Fluctuation 4.2.3 Monolayer Hydration 4.2.4 Contact Class 4.3 Local Patterns in Protein Hydration 4.3.1 Patterns on Hydrophilic Surfaces 4.3.2 Hydration Patterns on Hydrophobic Surfaces 4.3.3 Tetrahedral Hydrogen Bond Geometry of Water Molecules 4.4 Hydration Structures in Molecular Dynamics Simulation 4.4.1 Computation of Solvent Density 4.4.2 Characteristics of Solvent Density References 5 Structural Characteristics in Local Hydration 5.1 Introduction 5.2 Empirical Hydration Distribution Around Polar Atoms 5.2.1 Construction 5.2.2 Distribution Around Polar Protein Atoms 5.2.3 Hydration of Aromatic Acceptors 5.2.4 Characteristics and Benefits of the Empirical Hydration Distributions 5.2.5 Tetrahedral Hydrogen Bond Geometry 5.3 Assessment of Force Fields of Polar Protein Atoms 5.3.1 Models of Water Molecule Suitable for Simulation 5.3.2 Hydration of Deprotonated Polar Atoms in sp2-Hybridization 5.3.3 Hydration of Protonated Nitrogen Atoms in sp2- or sp3-Hybridization 5.3.4 Hydration of Protonated Oxygen Atoms in sp2- or sp3-Hybridization 5.3.5 Molecular Dynamics Simulation of Proteins Using Force Field with Lone-Pair Electrons References 6 Prediction of Hydration Structures 6.1 Introduction 6.2 Computation of Probability Distribution of Hydration Water Molecules [19] 6.3 Prediction for Soluble Protein [19] 6.3.1 On Solvent-Exposed Surfaces and in Cavities 6.3.2 At Interface in Protein Complex 6.4 Prediction for Membrane Proteins 6.4.1 For Surfaces of Membrane Proteins 6.4.2 For Channels in Transmembrane Regions 6.5 Accuracy of Prediction 6.6 Comparison of the Prediction with Theory of Liquids 6.7 Utilization of Probability Distribution in Structure Analysis 6.7.1 Assessment on Hydration Water Sites 6.7.2 Probability Distribution-Weighted Electron Density Map [55] 6.8 Prediction of Hydration Structures on Hydrophobic Surfaces References 7 Network of Hydrogen Bonds Around Proteins 7.1 Introduction 7.2 Network of Hydrogen Bonds 7.2.1 Chain Connection of Hydrogen Bonds 7.2.2 Percolation Property 7.3 Probability of Hydrogen Bond Formation 7.4 Network of Hydrogen Bonds in Simulation Trajectory 7.5 Influence of Networks of Hydrogen Bonds on Protein Motions References 8 Dipole–Dipole Interactions in Hydration Layer 8.1 Introduction 8.2 Orientational Ordering of Hydration Water Molecules 8.2.1 Coherent Patterns of Time-Averaged Water Dipoles 8.2.2 Solvent Dipole and Network of Hydrogen Bonds 8.2.3 Solvent Dipole in Drug Design 8.2.4 Poisson-Boltzmann Equation and Orientation Ordering of Water Molecules 8.3 Fluorescence from Tryptophan Side Chains Exposed to Solvent 8.3.1 Fluorescence from Photo-Excited Tryptophan of Protein 8.3.2 Interpretation of Dynamic Stokes Shift 8.3.3 Orientation Ordering of Water Molecules Around Tryptophan Side Chains 8.3.4 Origin of Dynamic Stokes Shift References 9 Hydration Structure Changes of Proteins at Work 9.1 Introduction 9.2 Experimental Evidence on Hydration-Regulated Protein Motion 9.2.1 Domain Motion in Glutamate Dehydrogenase 9.2.2 Hydration Structure Changes in Domain Motion 9.2.3 Model for Hydration Coupled Domain Motion 9.3 Molecular Mechanism in Hydration-Coupled Domain Motion 9.3.1 Domain Motion Observed in Simulation 9.3.2 Simultaneous Changes in Conformation and Hydration 9.3.3 Hydration Changes in the Hydrophobic Pocket 9.3.4 Drying Transition in the Hydrophobic Pocket 9.3.5 Hydration Changes in the Hydrophilic Crevice 9.3.6 Mechanism of Hydration Regulated Domain Motion 9.4 Manipulation of Conformation and Hydration of Proteins in the Crystals 9.4.1 Conformational Changes of Protein in Different Molecular Packing 9.4.2 Hydration Changes in Different Molecular Packing References 10 Energy Landscape and Hydration of Proteins 10.1 Introduction 10.1.1 Protein Conformation Manifold and Energy Landscape 10.2 X-Ray Diffraction Imaging 10.2.1 Structure Analysis Using X-Ray Diffraction Imaging 10.2.2 X-Ray Diffraction Imaging Using X-Ray Laser 10.3 Cryogenic Electron Microscopy 10.3.1 Classification of Protein Structures 10.3.2 Energy Landscape in Protein Motions 10.3.3 Prediction of Hydration Structures Using Neural Networks 10.4 Future Prospects References Appendix A Appendix B X-Ray Diffraction by a Crystal B.1 Thomson Scattering [B1] B.2 Interference of X-Rays Emitted by Electrons B.3 Diffraction From a Crystal [B3] B.4 The Ewald Sphere References Appendix C The Image Obtained by Electron Microscopy C1. Electron Scattering by a Weak-Phase Object [C1, C2] C2. Contrast Transfer Function [C1, C2] References Appendix D The Principle of the Up-Conversion Method D.1 Higher-Order Dielectric Polarization D.2 Radiation by Nonlinear Dielectric Polarization [D2, D3] D.3 The Phase-Matching Condition and Birefringence [D2, D3] References Appendix E The Symplectic Integrator Appendix F The Geometries of the Polar Groups in Amino Acid Residues Reference Appendix G Examples of Force Field Parameters Incorporating Lone-Pair Electrons for Deprotonated Oxygen and Nitrogen Atoms in the sp2-Hybridization Reference Appendix H Energy Relaxation of Perturbed System Reference Appendix I Surface Topography of Protein Crystals by Atomic Force Microscopy References Appendix J The Phase Retrieval Algorithm Used in X-Ray Diffraction Imaging References Appendix K Derivation of the Formula to Determine Appearance Frequencies of Model Structures in Electron Micrographs Reference Index