Computational Enzymology: Insights into Enzyme Mechanism and Catalysis from Modelling

Abstract

Modern modelling methods can now give a uniquely detailed understanding of enzyme-catalysed reactions, including analysing mechanisms and identifying determinants of specificity and catalytic efficiency. A new field of computational enzymology has emerged, which has the potential to contribute significantly to structure-based design, and in developing predictive models of drug metabolism; for example, in predicting the effects of genetic polymorphisms. This review outlines important techniques in this area, including quantum chemical model studies, and combined quantum mechanics/molecular mechanics (QM/MM) methods. Some recent applications to enzymes of pharmacological interest are also covered, showing the types of problems that can be tackled, and the insight they can give.