PROTEIN-SOLVENT INTERACTIONS. Roger B. Gregory

Transcription

1 PROTEIN-SOLVENT INTERACTIONS Roger B. Gregory

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3 Preface Contributors iii xvii 1. The New Paradigm for Protein Research Rufus Lumry 1 I. Introduction 1 A. Purposes 1 B. Confusing Biology with Chemistry 8 C. Supporting Evidence 9 II. Protein Structure 10 A. Information from B Factors 10 B. Observations Based on B Factors 1 2 C. Information from Proton-Exchange Studies 2 8 D. Information About Groups from Evolution and Genetics 36 E. Information from Density Data 39 III. How Substructures Determine Gestalt Structure and Properties 39 A. Genetic Stability 39 B. Kinetic Stability 40 C. Thermodynamic Stability 45 D. "Molten-Globule" Conformation States 5 3 E. Structural Dependence of Common Experimental Observables 5 4 IV. Some Devices that Became Possible After the Discovery of the Knot-Matrix Construction Principle 56

4 A. Modular Construction of Knot-Matrix Proteins 5 6 B. Expansion-Contraction Processes 5 6 C. Free Volume and Dielectric Constant 5 7 D. The "Pairing Principle" 5 8 E. "Completing the Knot" 5 9 F. Protein Activity Coefficients : Gibbs-Duhem Consequences 62 G. Intermolecular Communication Through Surfaces 6 7 V. Some Thermodynamic Topics of Special Importance for Biology 69 A. Weak Relationship Between Free Energy and It s Temperature and Pressure Derivatives 69 B. Enthalpy-Entropy Compensation Behavior 7 5 VI. Conformational Dynamics and "Dynamic Matching" 82 A. The Facts 82 B. Protein-Protein Association 9 1 C. The Oxygen-Binding Mechanism of Hemoglobins 94 D. Enzyme Mechanisms : Updating the Rack Mechanism 100 E. The Kunitz Proteinase Inhibitors 11 7 F. The Immune Reaction 11 8 VII. Dynamical Aspects of Protein Electrostatic Potentials 123 A. The Next Level of Complexity 123 B. What Is the Atomic Description of a Knot? 12 3 C. What Factors Are Responsible for the Stability of Knots? 124 D. Gestalt Versus Local Fields 12 6 VIII. Summary 12 9 A. Thermodynamics in the Biosphere 12 9 B. The Evolution of Devices 13 0 C. Function Follows Form? 13 1 D. Consequences for the Immediate Future of Protei n Chemistry 13 3 E. Hypotheses Based on the Knot-Matrix Principle 134 References Solvent Interactions with Proteins as Revealed by X-Ra y Crystallographic Studies Edward N. Baker 14 3 I. Introduction 14 3 II. Solvent Content of Protein Crystals 144 III. Crystallographic Location of Solvent 145 A. The Crystallographic Method 145 B. Identification and Refinement of Solvent Sites 146 C. Chemical Identity of Solvent Molecules 150

5 IV. Patterns of Solvent Structure 15 1 A. The General Picture 15 1 B. Hydration of Protein Groups 154 C. Internal Solvent Molecules 15 7 D. Surface Solvent Structure 16 2 E. Association with Secondary Structures 16 7 F. Solvent in Active Sites 17 2 V. Significance of Bound Solvent 174 A. Conservation of Solvent Sites 174 B. Contributions to Stability 178 C. Functional Roles of Solvent Molecules 180 VI. Bound Ions and Other Solvent Molecules 18 2 VII. Conclusions 18 5 References Protein Hydration and Glass Transition Behavior Roger B. Gregory 19 1 I. Introduction 19 1 II. Preparation of Solid State Samples 19 3 III. Adsorption of Water Vapor by Proteins : The Sorption Isotherm 19 3 A. Conventional Sorption Isotherms 195 B. Site Heterogeneity and Conformational Perturbations 19 8 C. Sorption Hysteresis 20 1 IV. Identification and Coverage of Sorption Sites and Som e Critical Hydration Levels in the Sorption Isotherm 205 A. Infrared Spectroscopic Studies of Protein Hydration 206 B. Heat Capacity as a Function of Hydration 207 C. Enzyme Activity 21 0 D. Proton Percolation 21 1 E. Nonfreezing Water 21 4 F. The Effect of Hydration on Thermal Stability 21 5 G. Protein Surface Areas and Monolayer Coverage 21 7 V. Hydration-Induced Conformational Changes 21 7 A. Solid State 13C NMR Studies of Protein Hydration 21 8 B. An X-Ray Diffraction Study of a Dehydrated Protein 219 C. FTIR Studies of Dehydration-Induced Conformational Transitions 220 VI. Effect of Hydration on Protein Dynamics 22 1 A. Spectroscopic Methods 22 1 B. Hydrogen Isotope Exchange 22 4 C. Positron Annihilation Lifetime Spectroscopy 225

6 VII. Glass Transitions in Proteins 227 A. Glass Transition Behavior in Polymers 227 B. Free Volume in Glass Transition Theory 230 C. The 200 K Transition in Fully Hydrated Proteins 23 2 D. Hydration Dependence of Glass Transition Temperatures 23 3 E. Hysteresis Effects 236 VIII. Dynamically Distinct Structural Classes in Globular Proteins 23 7 A. Evidence from Hydrogen Isotope Exchange 23 8 B. The Basis of Knot Formation 242 C. The Connection Between Hydrogen Exchange Propertie s and Glass Transition Behavior 245 D. "Molten Globule" and Cold-Denatured States 249 IX. Protein Folding 249 X. Conclusions 25 7 References Dielectric Studies of Protein Hydration Ronald Pethig 265 I. Introduction 26 5 II. Dielectric Theory and Measurements 26 6 III. Experimental Results 27 3 A. Protein Solutions 27 3 B. Solid State Studies 27 5 C. Water as Plasticizer 27 7 D. Proton Conduction Effects 28 1 IV. Concluding Remarks 28 5 References Protein Dynamics : Hydration, Temperature, and Solvent Viscosit y Effects as Revealed by Rayleigh Scattering of Mossbauer Radiatio n Vitalii I. Goldanskii and Yurii F. Krupyanskii 289 I. Introduction 289 II. Background of RSMR Technique, Basic Expressions, an d Approximations 290 III. Hydration Dependencies of the Elastic RSMR Fractions an d RSMR Spectra 296 IV. Solvent Composition and Viscosity Dependencies of the Elasti c RSMR Fractions 300 V. Temperature Dependencies of the Elastic RSMR Fraction an d RSMR Spectra 305 VI. Angular Dependencies of Inelastic RSMR Intensities 306

7 VII. Properties of Protein-Bound Water 30 9 VIII. Dynamical Properties of Hydrated Proteins 314 IX. Principal Conclusions and Outlook 32 1 References Proteins in Essentially Nonaqueous Environments Darrell L. Williams, Jr., Igor Rapanovich, and Alan J. Russell 32 7 I. Introduction 32 7 II. "Anhydrous" and Heterogeneous Systems 33 2 III. "Anhydrous" and Homogeneous Systems 33 5 IV. Water/Cosolvent Mixtures 33 7 V. Conclusions 33 9 References Solvent Viscosity Effect on Protein Dynamics : Updating the Concepts Benjamin Gavish and Saul Yedgar 343 I. Introduction 343 II. Brownian Dynamics 344 A. Basics 345 B. Generalized Approach 349 C. Free Volume 35 6 III. Barrier Crossing 35 8 A. Basic Concepts 35 8 B. Models 35 9 IV. Viscosity Effect 36 3 A Kinetic Studies 36 3 B. Ultrasonic Studies 364 V. Why a Power Law? 36 8 VI. Conclusions 36 9 References Effect of Solvent on Protein Internal Dynamics : The Kinetic s of Ligand Binding to Myoglobin Wolfgang Doster, Thomas Kleinert, Frank Post, and Marcus Settles 37 5 I. Introduction 375 IL The Flash Photolysis Experiment 37 7 III. The Kinetics of CO Binding to Myoglobin 37 8 IV. The Surface Barrier 380 V. The Internal Barriers 382

8 VI. Conclusion 38 3 References Solvent Effects on Protein Stability and Protein Association 38 7 Arieh Ben-Naim I. Introduction : A Historic Perspective 38 7 II. Protein Folding and Protein-Protein Association 39 0 HI. Direct and Indirect Interactions 396 IV. Driving Force, Force, and Stability 40 1 V. Inventory of Solvent-Induced Effects 407 VI. The Missing Information and How to Obtain It 41 3 A. The Solvation Gibbs Energy of the Large Linear Polypeptide Having No Side Chains 41 3 B. Solvation of the Backbone of the F Form 414 C. Loss of the Conditional Solvation Gibbs Energies o f the Various Side Chains 414 D. Pairwise Correlations 41 5 E. Higher-Order Correlations 41 6 VII. Concluding Remarks 41 7 References Thermodynamic Mechanisms for Enthalpy-Entropy Compensation Ernest Grunwald and Lorrie L. Comeford 42 1 I. Introduction 42 1 II. Experimental Examples 42 2 III. Interaction Mechanisms and Compensation Vecto r Diagrams 42 3 IV. Examples of Partial Compensation 42 5 V. Thermodynamic Compensation 427 A. Molecular Species 428 VI. Mathematical Formulation 43 1 A. Standard Partial Enthalpies and Entropies in Dilute Solutions 43 3 B. Molar-Shift Mechanism 43 3 C. Solvation Mechanism 435 VII. Application to Nonpolar Solutes in Water 438 A. Delphic Dissection of Standard Partial Entropies 43 9 VIII. Concluding Remarks 44 1 References 442

9 11. Preferential Interactions of Water and Cosolvents with Protein s Serge N. Timasheff 44 5 I. Introduction 44 5 II. Cosolvent Control of Protein Solution Stability and State of Dispersion 446 A. Binding of Cosolvent and Displacement of Reactio n Equilibria 446 B. What Is Binding? 447 C. Cosolvent Effects on Equilibria Relative to Water 448 III. Relation Between Preferential Interactions and Transfer Free Energy 44 9 A. Thermodynamic Definition of Binding 44 9 B. Binding Is Replacement of Water by Ligand at a Site 45 0 C. The Wyman Slope Is the Change in Thermodynami c Interaction 45 1 D. Relation Between Transfer Free Energy and Preferentia l Interaction 45 2 IV. How Transfer Free Energy Modulates Protein Reactions 45 3 A. Precipitation 45 3 B. Structure Stabilization-Destabilization 45 5 C. Why Precipitants Are Not Necessarily Stabilizers 46 1 V. Preferential Interactions and Binding at Sites 46 1 A. Classical Site Binding Theory 46 2 B. Inadequacy of the Site Binding Treatment 46 2 C. Preferential Binding as Exchange at Sites : Weak and Strong Binding 463 D. Preferential Binding as the Balance Between Water an d Ligand Binding to a Protein: Meaning of Zero "Binding" 46 5 E. Meaning of Thermodynamic Indifference 46 7 F. Relation Between Global Preferential Interactions an d Exchange at Sites 46 7 G. Direct Site Occupancy Measurements Cannot Define th e Thermodynamic Interaction 470 H. Weak Effects as Results of Strong Interactions at Sites 47 1 VI. Meaning of Sites in Weak Binding 474 VII. Why Are Some Cosolvents Preferentially Exclude d from Protein? 47 5 VIII. Conclusion : Competition, Compensation, Binding-Exclusion Balance 47 8 References 479

10 12. Thermodynamic Nonideality and Protein Solvatio n Donald J. Winzor and Peter R. Wills 483 I. Introduction 483 II. Quantitative Interpretation of Partial Specific Volumes 484 A. Traditional Approach 48 4 B. Choice of Concentration Scale 486 C. Direct Thermodynamic Interpretation 489 D. Equivalence of Treatments 49 1 III. Virial Coefficients from Density Measurements 492 A. Protein-Small Nonelectrolyte Systems 493 B. Osmolytes as Inert Solute 495 C. Excluded Volume Interpretation 495 IV. Consideration of Small Solutes as Effective Spheres 496 A. Interpretation of Isopiestic Measurements 49 6 B. Freezing Point Depression Data 500 C. Frontal Gel Chromatography of Sucrose 500 D. Validity of the Proposition 502 V. Effective Thermodynamic Radii of Globular Proteins 503 A. Evaluation from Self-Covolume Measurements 504 B. Evaluation from Protein-Small Solute Covolume 507 C. Relationship to the Stokes Radius 508 VI. Effects of Small Solutes on Protein Isomerization 51 0 A. ph-induced Unfolding of Proteins 51 2 B. Ligand-Induced and Preexisting Isomerizations 51 3 C. Thermal Unfolding of Proteins 51 5 VII. Concluding Remarks 516 References Molecular Basis for Protein Separations Rex E. Lovrien, Mark J. Conroy, and Timothy I. Richardson 52 1 I. Introduction 52 1 II. Protein Reactivity and Conformation Governance in Separations 524 III. The Plasma Albumin Prototype : Conformation Behavior, Reactivity Toward Ligands, Consequences i n Coprecipitation, and Cocrystallization 526 IV. Salt Counterion Contraction of Proteins from Acid - Expanded Conformation 528 V. Cocrystallization of Proteins with Inorganic and Organic Ionic Ligands 530

11 VI. Water Inside, Water Outside Proteins 53 3 VII. Protein Precipitation from Four-Carbon Cosolvent, t-butanol 53 6 VIII. Matrix Coprecipitation by Organic Ion Ligands 54 0 IX. Inorganic and Organic Ion-Binding Thermochemistry 54 6 References 55 0 Index 555