Computer Modeling of Chemical Reactions in Enzims and Solutions (Warshel A.)

Computer Modeling of Chemical Reactions in Enzims and Solutions

Автор(ы):Warshel A.
06.10.2007
Год изд.:1991
Описание: The book can be used in a one semester course for senior undergraduate and graduate students who are interested in understanding physical aspects of biochemistry and computer modeling of macromolecules. It can also be used as a self-study text and as a complement to other books. Although it follows a rigorous introductory outline, this book does not require significant prior knowledge, and many of the principles taught in the first three chapters can be adopted as working recipes even without a full understanding of their exact derivations. Several specific examples of enzymatic reactions are presented and analyzed to illustrate the approaches needed for simulating such reactions. These examples can be followed conveniently in studies of other systems. Many problems and computer exercises are provided to help readers test their understanding of actual modeling concepts and prepare them to handle larger molecular simulation packages in studies of biophysical problems.
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Computer Modeling of Chemical Reactions in Enzims and Solutions — обложка книги. Обложка книги.
1. BASIC PRINCIPLES OF CHEMICAL BONDING [1]
  1.1. The Isolated Atom [1]
    1.1.1. The Schroedinger Equation [2]
    1.1.2. Wave Functions for Atoms [3]
    1.1.3. Valence Electrons and the Core/Valence Separation [4]
  1.2. Molecular Orbitals for Diatomic Molecules [4]
    1.2.1. The MO Potential Surface for the H^ Molecule [5]
    1.2.2. MO Potential Surface for Molecules with Many Valence Electrons [7]
    1.2.3. Solution of Secular Equations by Matrix Diagonalization [11]
    1.2.4. Incorporating the Effect of External Charges in MO Treatments [12]
  1.3. The Valence Bond Description of Diatomic Molecules [14]
    1.3.1. The Heitler-London Treatment of the H(?) Molecule [15]
    1.3.2. Adding Ionic Terms [17]
    1.3.3. Semi-empirical Parametrization of the VB Hamiltonian [18]
    1.3.4. Molecular Dipole Moment [22]
  1.4. Small Polyatomic Molecules [23]
  1.5. Appendix A—Molecular Orbital Treatment of Many-Electron Systems [27]
  1.6. Some Relevant Computer Programs [31]
      References [39]
2. CHEMICAL REACTIONS IN THE GAS PHASE AND IN SIMPLE SOLVENT MODELS [40]
  2.1. Reaction Rate in the Gas Phase [40]
    2.1.1. Equilibrium Constant and Rate Constants [40]
    2.1.2. The Rate Constants for Many-Dimensional Systems [43]
  2.2. VB Potential Surfaces for Reactions in Solutions [46]
    2.2.1. General Considerations [46]
    2.2.2. The Langevin Dipoles Model [49]
    2.2.3. LD Calculations of VB Potential Surfaces [51]
  2.3. MO Potential Surfaces for Reactions in Solutions [54]
  2.4. Proton Transfer Reactions and the EVB Model [55]
    2.4.1. VB Potential Surface for Proton Transfer Reactions in Solutions [55]
    2.4.2. The EVB Calibration Procedure [58]
  2.5. Appendix B—Four Electrons/Three Orbitals VB Treatment [59]
  2.6. Some Relevant Computer Programs [63]
      References [73]
3. CHEMICAL REACTION IN ALL-ATOM SOLVENT MODELS [74]
  3.1. All-Atom Solvent Models [74]
    3.1.1. Explicit Models for Water Molecules [74]
    3.1.2. How to Obtain Refined Potential Surfaces for the Solvent Molecules [76]
  3.2. Exploring the Solvent Phase Space by the Method of Molecular Dynamics [76]
    3.2.1. Statistical Mechanics and the Relationship Between Macroscopic and Microscopic Properties [76]
    3.2.2. Molecular Dynamics and Simulations of Average Solvent Properties [77]
  3.3. Calculation of Solvation Energies by Free-Energy Perturbation Methods [80]
    3.3.1. Direct Calculations of Free Energy Converge Very Slowly [80]
    3.3.2. Perturbation Calculations of Free-Energy Changes [81]
  3.4. Combining Solvent Effects with Quantum Mechanical Solute Calculations [83]
  3.5. Evaluation of Activation-Free Energies [87]
    3.5.1. The EVB Mapping Potential [87]
    3.5.2. Obtaining the Free-Energy Functions [88]
  3.6. Examining Dynamical Effects [90]
  3.7. Linear Free-Energy Relationships [92]
  3.8. Some Relevant Computer Programs [96]
      References [108]
4. POTENTIAL SURFACES AND SIMULATIONS OF MACROMOLECU LES [109]
  4.1. Background [109]
  4.2. Force Fields for Large Molecules [111]
    4.2.1. The Forces in Macromolecules Can Be Described by Simple Functions [111]
    4.2.2. Refining the Parameters in Molecular Force Fields [112]
  4.3. Energy Minimization [113]
    4.3.1. The Steepest Descent Method [113]
    4.3.2. Converging Minimization Methods [114]
  4.4. Normal Modes Analysis of Large Molecules [117]
  4.5. Molecular Dynamics and Phase Space Exploration [119]
    4.5.1. Thermal Amplitudes [119]
    4.5.2. Diffusion Constants and Autocorrelation Times [120]
    4.5.3. Free Energies of Macromolecules [122]
  4.6. Electrostatic Free-Energies and Dielectric Effects in Macromolecules [122]
    4.6.1. The Protein Dipoles-Langevin Dipoles (PDLD) Model [123]
    4.6.2. Surface-Constrained Solvent Model for Macromolecules [126]
  4.7. Some Relevant Computer Programs [128]
      References [135]
5. MODELING REACTIONS IN ENZYMES: AN INTRODUCTION [136]
  5.1. Enzyme Kinetics and Free-Energy Surfaces [137]
    5.1.1. Basic Concepts of Enzyme Kinetics [137]
    5.1.2. The Relationship Between Enzyme Kinetics and Apparent Activation Free Energy [138]
  5.2. PDLD Simulations of Proton Transfer Reactions in Enzymes [140]
    5.2.1. The His-Cys Ion Pair in Papain as a Model System [140]
    5.2.2. Calibrating the Enzyme. Surf ace Using Solution Experiments [143]
  5.3. All-Atom Models for Proton Transfer Reactions in Enzymes [146]
  5.4. Linear Free-Energy Relationship in Enzymes [148]
  5.5. Some Relevant Computer Programs [149]
      References [152]
6. GENERAL ACID CATALYSIS AND ELECTROSTATIC STABILIZATION IN THE CATALYTIC REACTION OF LYSOZYME [153]
  6.1. Background [153]
  6.2. The Strain Hypothesis and Protein Flexibility [155]
  6.3. Modeling Chemistry and Electrostatic Effects [158]
    6.3.1. A Simple VB Formulation [158]
    6.3.2. Calibrating the EVB Surface Using the Reference Reaction in Solution [162]
    6.3.3. Examination of the Catalytic Reaction in the Enzyme-Active Site [167]
      References [169]
7. SERINE PROTEASES AND THE EXAMINATION OF DIFFERENT MECHANISTIC OPTIONS [170]
  7.1. Background [170]
  7.2. Potential Surfaces for Amide Hydrolysis in Solution and in Serine Proteases [173]
    7.2.1. The Key Resonance Structures for the Hydrolysis Reaction [173]
    7.2.2. Calibrating the Potential Surface [176]
  7.3. Examining the Charge-Relay Mechanism [182]
  7.4. Site-Specific Mutations Provide a Powerful Way of Exploring Different Catalytic Mechanisms [184]
      References [188]
8. SIMULATING METALLOENZYMES [189]
  8.1. Staphylococcal Nuclease [189]
    8.1.1. The Reaction Mechanism and the Relevant Resonance Structures [189]
    8.1.2. The Construction of the EVB Potential Surface for the Reaction [192]
    8.1.3. The Ca(?) Ion Provides Major Electrostatic Stabilization to the Two High-Energy Resonance Structures [195]
  8.2. Carbonic Anhydrase [197]
  8.3. General Aspects of Metalloenzymes [201]
    8.3.1. Linear Free-Energy Relationships for Metal Substitution [201]
    8.3.2. Classification of Metalloenzymes in Terms of the Interplay Between the General Base and the Metal [205]
      References [207]
9. HOW DO ENZYMES REALLY WORK? [208]
  9.1. Introduction [208]
  9.2. Factors That Are Not So Effective in Enzyme Catalysis [209]
    9.2.1. It Is Hard to Reduce Activation Free Energies in Enzymes by Steric Strain [209]
    9.2.2. The Feasibility of the Desolvation Hypothesis Can Be Examined with Clear Thermodynamic Considerations [211]
    9.2.3. Dynamical Effects and Catalysis [215]
  9.3. What About Entropic Factors? [217]
    9.3.1. Entropic Factors Should be Related to Well-Defined Potential Surfaces [217]
    9.3.2. Entropic Factors in Model Compounds and Their Relevance to Enzyme Catalysis [221]
  9.4. Electrostatic Energy is the Key Catalytic Factor in Enzymes [225]
    9.4.1. Why Electrostatic Interactions Are So Effective in Changing (?) [225]
    9.4.2. The Storage of Catalytic Energy and Protein Folding [226]
      References [228]
INDEX [229]
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