title: In silico methods for predicting ligand binding determinants of cytochromes P450.
abstract: A large number of computational methodologies have been used to predict, and thus help explain, the metabolism catalysed by the enzymes of the cytochrome P450 superfamily (P450s). A summary of the methodologies and resulting models is presented. This shows that investigations so far have focused on just a few of the many P450s, mainly those that are involved in drug metabolism. The models have evolved from simple comparisons of known substrates to more elaborate models requiring considerable computer power. These help to explain and, more importantly, predict the involvement of P450s in the metabolism of specific compounds.
authors.affiliation: Department of Medicinal Informatics, Structure & Design, Pfizer Global Research & Development, Sandwich Laboratories, Kent CT13 9NJ, UK. marcel.degroot@pfizer.com
authors.forename: Marcel J
authors.initials: MJ
authors.lastname: de Groot
authors.forename: Stewart B
authors.initials: SB
authors.lastname: Kirton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sutcliffe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D039301:Computers, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D016415:Sequence Alignment
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System