Computational Approaches to Biochemical Reactivity

1. Front Matter

   Pages i-x

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2. Quantum Mechanical Models for Reactions in Solution

   • J. Tomasi, B. Mennucci, R. Cammi, M. Cossi

   Pages 1-102

3. Free Energy Perturbation Calculations within Quantum Mechanical Methodologies

   • Robert V. Stanton, Steven L. Dixon, Kenneth M. Merz Jr.

   Pages 103-123

4. Hybrid Potentials for Molecular Systems in the Condensed Phase

   • Martin J. Field

   Pages 125-151

5. Molecular Mechanics and Dynamics Simulations of Enzymes

   • Roland H. Stote, Annick Dejaegere, Martin Karplus

   Pages 153-198

6. Electrostatic Interactions in Proteins

   • Kim A. Sharp

   Pages 199-235

7. Electrostatic Basis of Enzyme Catalysis

   • G. Náray-Szabó, M. Fuxreiter, A. Warshel

   Pages 237-293

8. On the Mechanisms of Proteinases

   • A. Goldblum

   Pages 295-340

9. Modelling of Proton Transfer Reactions in Enzymes

   • Johan Åqvist

   Pages 341-362

10. Protein-Ligand Interactions

    • Terry P. Lybrand

    Pages 363-374

11. Back Matter

    Pages 375-380

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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.

• biology
• biophysics
• catalysis
• enzyme
• enzymes
• mechanics
• protein
• proteins
• structural biology

• Department of Theoretical Chemistry, Eötvös Loránd University, Budapest, Hungary

  Gábor Náray-Szabó

• Department of Chemistry, University of Southern California, Los Angeles, USA

  Arieh Warshel

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