Computational Approaches to Biochemical Reactivity

A quantitative description of the action of enzymes and other biological systems is both a challenge and a fundamental requirement for further progress in our und- standing of biochemical processes. This can help in practical design of new drugs and in the development of artificial enzymes as well as in fundamental understanding of the factors that control the activity of biological systems. Structural and biochemical st- ies have yielded major insights about the action of biological molecules and the mechanism of enzymatic reactions. However it is not entirely clear how to use this - portant information in a consistent and quantitative analysis of the factors that are - sponsible for rate acceleration in enzyme active sites. The problem is associated with the fact that reaction rates are determined by energetics (i. e. activation energies) and the available experimental methods by themselves cannot provide a correlation - tween structure and energy. Even mutations of specific active site residues, which are extremely useful, cannot tell us about the totality of the interaction between the active site and the substrate. In fact, short of inventing experiments that allow one to measure the forces in enzyme active sites it is hard to see how can one use a direct experimental approach to unambiguously correlate the structure and function of enzymes. In fact, in view of the complexity of biological systems it seems that only computers can handle the task of providing a quantitative structure-function correlation.

Klappentext

This book summarises recent results in the rapidly developing discipline of the computational aspects of biochemical reactivity. It presents a comprehensive and critical treatise on the subject, with numerous references covering practically all relevant and recent work. The chapters, written by eminent experts in the field, deal with quantum mechanical models for reactions in solution, ab initio molecular orbital studies on enzymatic reactions, combined quantum-classical models for proteins, force field approaches for modelling enzymes, electrostatic effects in proteins, electrostatic basis of enzyme catalysis, the mechanism of proteases, modelling of proton transfer reactions in enzymes and protein-ligand interactions. Audience: This volume will be of interest to graduate students and researchers working in molecular biophysics, structural biology or structure-based molecular design. TOC:Preface.- 1. Quantum Mechanical Models for Reactions in Solution.- 2. Free Energy Perturbation Calculations within Quantum Mechanical Methodologies.- 3. Hybrid Potentials for Molecular Systems in the Condensed Phase.- 4. Molecular Mechanics and Dynamics Simulations of Enzymes.- 5. Electrostatic Interactions in Proteins.- 6. Electrostatic Basis of Enzyme Catalysis.- 7. On the Mechanisms of Proteinases.- 8. Modelling of Proton Transfer Reactions in Enzymes.- 9. Protein-Ligand Interactions.- Subject Index.

Inhalt
Quantum Mechanical Models for Reactions in Solution.- Free Energy Perturbation Calculations within Quantum Mechanical Methodologies.- Hybrid Potentials for Molecular Systems in the Condensed Phase.- Molecular Mechanics and Dynamics Simulations of Enzymes.- Electrostatic Interactions in Proteins.- Electrostatic Basis of Enzyme Catalysis.- On the Mechanisms of Proteinases.- Modelling of Proton Transfer Reactions in Enzymes.- Protein-Ligand Interactions.