title: Modelling enzyme reaction mechanisms, specificity and catalysis.
abstract: Modern modelling methods can now give uniquely detailed understanding of enzyme-catalyzed reactions, including the analysis of mechanisms and the identification of determinants of specificity and catalytic efficiency. A new field of computational enzymology has emerged that has the potential to contribute significantly to structure-based design and to develop predictive models of drug metabolism and, for example, of the effects of genetic polymorphisms. This review outlines important techniques in this area, including quantum-chemical model studies and combined quantum-mechanics and 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.
authors.affiliation: Centre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, UK. Adrian.Mulholland@bris.ac.uk
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland
mesh_terms: D002384:Catalysis; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory; D013379:Substrate Specificity; D009626:Terminology as Topic
chemical_list: D004798:Enzymes