Front Cover 1
Advances in Protein Chemistry, Volume 51 4
Copyright Page 5
Contents 6
Introduction 10
Chapter 1. Electrostatic Contributions to Molecular Free Energies in Solution 12
I. Introduction 12
II. Theory and Calculational Methods 14
III. Applications 31
IV. Outlook 64
References 65
Chapter 2. Site-Specific Analysis of Mutational Effects in Proteins 70
I. Introduction 70
II. The Reference Cycle 72
III. Structural Mapping of Energetics 74
IV. Site-Specific Analysis of Mutational Effects in Proteins 84
V. Site-Specific Dissection of Thrombin Specificity 90
VI. Concluding Remarks 124
References 126
Chapter 3. Allosteric Transitions of the Acetylcholine Receptor 132
I. Introduction 132
II. Mechanistic Models 138
III. Recovery from Desensitization 144
IV. Kinetic Basis of Dose–Response Curves 148
V. Multiple Phenotypes 152
VI. Deductions from Single-Channel Measurements 160
VII. Allosteric Effectors and Coincidence Detection 174
VIII. General Considerations 177
References 184
Chapter 4. Deciphering the Molecular Code of Hemoglobin Allostery 196
I. Introduction 196
II. Overview 201
III. Binding Curves and Stoichiometric Information 209
IV. Site-Specific Aspects of Oxygen Binding 217
V. Experimental Determination of Site-Specific Cooperativity Terms 222
VI. How the Molecular Code Was Deciphered 232
VII. Concluding Remarks 257
References 259
Chapter 5. Statistical Thermodynamic Linkage between Conformational and Binding Equilibria 266
I. Introduction 266
II. The Most Probable Distribution 268
III. Coupling of Statistical Weights to Ligands 268
IV. Modulation of Distribution of States by Specific Ligands 270
V. Modulation of Distribution of States by Denaturants 273
VI. Ligand-Induced Conformational Changes 274
VII. The Distribution of Conformational States According to Their Gibbs Energy 274
VIII. Is the Unfolded State the State with the Highest Gibbs Energy? 278
IX. The Gibbs Energy Scale of Conformational States 280
X. Statistical Descriptors of the Conformational Ensemble 282
XI. Conclusions 289
References 289
Chapter 6. Analysis of Effects of Salts and Uncharged Solutes on Protein and Nucleic Acid Equilibria and Processes: A Practical Guide to Recognizing and Interpreting Polyelectrolyte Effects, Hofmeister Effects, and Osmotic Effects of Salts 292
I. Introduction 293
II. Overview of Concentration-Dependent Effects of Perturbing Solutes on Processes Involving Biopolymers 297
III. Preferential Interaction Coefficients as Fundamental Measures of Thermodynamic Effects due to Solute–Biopolymer Interactions 306
IV. Preferential Interactions of Nonelectrolyte Molecules with an Uncharged Biopolymer 314
V. Preferential Interactions of Electrolyte Ions with a Charged Biopolymer 322
VI. Use of Three-Component Preferential Interaction Coefficients to Analyze Effects of Solute Concentration on Equilibrium Constants, Transition Temperatures, or Free Energy Changes of Biopolymer Processes 330
VII. Two-Domain Predictions of Functional Forms of Effects of Nonelectrolyte Concentration on Equilibria (Kobs) and Transition Temperatures ( Tm ) of Uncharged Biopolymers in Aqueous Solution 337
VIII. Polyelectrolyte and Two-Domain Predictions of Functional Forms of Effects of Salt Concentration on Equilibria (Kobs) and Transition Temperatures ( Tm ) of Charged Biopolymers in Aqueous Solution 341
IX. Conclusions and Future Directions 358
References 361
Chapter 7. Control of Protein Stability and Reactions by Weakly Interacting Cosolvents: The Simplicity of the Complicated 366
I. Introduction 367
II. Preferential Interactions 371
III. Wyman Linkages in Preferential Interactions 389
IV. Linkage Control of Protein Stability 398
V. Linkage Control of Protein Reactions 420
VI. Sources of Exclusion 427
VII. Osmolytes 434
VIII. Conclusion 436
References 439
Author Index 444
Subject Index 464