Note: Cover page -- Contents -- New Directions in the Study of Peptide H-Bonds and.Peptide Solvation -- Chapter 1: Potential Functions for Hydrogen Bonds in Protein Structure Prediction and Design -- I. Introduction -- II. Physical Mechanism of Hydrogen Bond Formation -- III. Main Approaches to Modeling Hydrogen Bonds in Biomolecular Simulations -- A. Potentials Derived from Hydrogen Bonding Geometries Observed in Crystal Structures -- B. Molecular Mechanics: Comparison with the Structure-Derived, Orientation-Dependent Potential -- C. Quantum Mechanics: Comparison with Molecular Mechanics and the Structure-Derived Potential -- IV. Applications of Hydrogen Bonding Potentials -- A. Protein Structure Prediction and Refinement -- B. Prediction of Protein-Protein Interfaces -- C. Protein Design -- V. Conclusions and Perspectives -- References -- Chapter 2: Backbone-Backbone H-Bonds Make Context-Dependent Contributions to Protein Folding Kinetics and Thermodynamics: Lessons from Amide-to-Ester Mutations -- I. Introduction -- II. Nomenclature and Synthesis of Amide-to-Ester Mutants -- III. Esters as Amide Replacements -- A. Geometry and Conformation -- B. Structural Effects of Amide-to-Ester Mutations -- IV. Interpretation of Energetic Data from Amide-to-Ester Mutants -- A. H-Bond Energies and the Thermodynamic Analysis of Amide-to-Ester Mutants -- B. Kinetic Analysis of Amide-to-Ester Mutants -- V. Amide-to-Ester Mutations in Studies of Protein Function -- VI. Amide-to-Ester Mutations in Studies of Protein Folding Thermodynamics -- VII. Analysis of DeltaDeltaGb and DeltaDeltaGf Values from Amide-to-Ester Mutants -- A. General Observations -- B. Quantitative Analysis of DeltaDeltaGf/b Values -- VIII. Amide-to-Ester Mutations in Studies of Protein Folding Kinetics -- IX. Conclusions and Future Directions -- References. , Chapter 3: Modeling Polarization in Proteins and Protein-ligand Complexes: Methods and Preliminary Results -- I. Introduction -- II. Incorporation of Polarization in Molecular Mechanics Models -- A. Overview -- B. Development of the OPLS/PFF Force Field -- C. Simulation Methodology -- D. Evaluation of the Polarizable Force Field in the Gas Phase and Condensed Phase -- III. Aqueous Solvation Models for Polarizable Simulations -- A. Overview -- B. Polarizable Explicit Water Models -- IV. Modeling Polarizability with Mixed Quantum Mechanics/Molecular Mechanics Methods -- A. Overview -- B. Protein-Ligand Docking Using a Mixed Mixed Quantum Mechanics/Molecular Mechanics Methodology to Compute Ligand Charges -- V. Protein Simulations in Explicit Solvent Using a Polarizable Force Field -- A. Overview -- B. Simulations of BPTI with Polarizable and Fixed Charge Protein and Water Models -- VI. Conclusion -- References -- Chapter 4: Hydrogen Bonds In Molecular Mechanics Force Fields -- I. Introduction -- II. Geometric Deformation -- III. Nonbonded Interactions -- IV. Conclusion -- References -- Chapter 5: Resonance Character of Hydrogen-bonding Interactions in Water and Other H-bonded Species -- I. Introduction -- II. Natural Bond Orbital Donor-Acceptor Description of H-Bonding -- III. Quantum Cluster Equilibrium Theory of H-Bonded Fluids -- IV. Recent Experimental Advances in Determining Water Coordination Structure -- V. General Enthalpic and Entropic Principles of H-Bonding -- A. Torsional, Angular, and Dissociative Entropic Contributions -- B. Binary and Cooperative Enthalpic Contributions -- VI. Hydrophobic Solvation: A Cluster Equilibrium View -- VII. Summary and Conclusions: The Importance of Resonance in H-Bonding and Its Possible Representation by Molecular Dynamics Simulations -- References. , Chapter 6: How hydrogen bonds shape membrane protein structure -- I. Introduction -- II. Structure of Fluid Lipid Bilayers -- III. Energetics of Peptides in Bilayers -- A. Folding in the Membrane Interface -- B. Transmembrane Helices -- IV. Helix-Helix Interactions in Bilayers -- V. Perspectives -- References -- Chapter 7: Peptide and Protein Folding and Conformational Equilibria: Theoretical Treatment of Electrostatics and Hydrogen Bonding with Implicit Solvent Models -- I. Introduction -- II. Generalized Born (GB) Models -- A. GB Electrostatics Theory -- B. Advances and Achievements -- C. Remaining Opportunities for Continued Improvement -- III. Peptide Folding and Conformational Equilibria -- A. Influence of Backbone H-Bond Strength on Conformational Equilibria -- B. Influence of Backbone Dihedral Energetics on Conformational Equilibria -- IV. Concluding Discussion -- References -- Chapter 8: Thermodynamics Of alpha-Helix Formation -- I. First 50 Years of Study of the Thermodynamics of the Helix-Coil Transition -- II. The Quest for Enthalpy of the Helix-Coil Transition -- III. Temperature Dependence of Enthalpy of the Helix-Coil Transition -- IV. Thermodynamic Helix Propensity Scale: Importance of Peptide Backbone Hydration -- V. Other Instances When Peptide Backbone Hydration is Important for Stability -- VI. Future Directions -- References -- Chapter 9: The Importance of Cooperative Interactions and a Solid-State Paradigm to Proteins: What Peptide Chemists Can Learn from Molecular Crystals -- I. Introduction -- II. Similarities and Differences Between Proteins/Peptides and Molecular Crystals -- A. Similarities -- B. Differences -- III. The Importance of H-Bond Cooperativity in Molecular Crystals -- A. Enthalpy Is Relatively More Important in the Solid Than in the Liquid -- B. H-Bonds Are More Stable in the Solid Than in the Liquid State. , IV. Structural Consequences of H-Bond Cooperativity in Molecular Crystals -- A. Acetic Acid -- B. 1,3-Cyclohexanedione -- C. Urea -- D. Formamide -- E. CH...O H-Bonding Interactions and Parabenzoquinone -- V. How Does the Use of the Crystal Paradigm Affect Protein/Peptide Study? -- A. Low-Barrier H-Bonds -- VI. Are H-Bonds Electrostatic? -- A. Water-Water H-Bonding Cannot be Described Adequately Purely by Electrostatic Interactions -- B. Comparison of H-Bonds with the Behavior of Molecules in an Electric Field -- VII. How Strong are Peptide H-Bonds? -- A. Amide Dimers -- B. Formamide Chains -- C. alpha-Helices -- D. Protonated alpha-Helices -- E. beta-Sheets -- F. Collagen-like Triple Helices -- VIII. Comparison with Experimental Data from Studies in Solution -- A. alpha-Helices -- IX. The Importance of a Suitable Reference State(s) -- A. Differences between Reference States for Experimental and Theoretical Studies -- B. Multiple Reference States -- C. Component Amino Acids -- D. Extended beta-Strand -- E. Choosing More Than One Reference State -- X. How Protein Chemists Can Deal with Problems Posed by Dual Paradigms -- A. Theoretical and Modeling Studies -- B. Experimental Studies -- XI. Water, the Hydrophobic Effect and Entropy -- A. Water -- B. The Hydrophobic Effect and Entropy -- C. Another Origin of Entropy Control of Protein Folding -- XII. Concluding Remarks -- References -- Author Index -- Subject Index.