title: Prediction of cytochrome P450 mediated metabolism.
abstract: Cytochrome P450 enzymes (CYPs) form one of the most important enzyme families involved in the metabolism of xenobiotics. CYPs comprise many isoforms, which catalyze a wide variety of reactions, and potentially, a large number of different metabolites can be formed. However, it is often hard to rationalize what metabolites these enzymes generate. In recent years, many different in silico approaches have been developed to predict binding or regioselective product formation for the different CYP isoforms. These comprise ligand-based methods that are trained on experimental CYP data and structure-based methods that consider how the substrate is oriented in the active site or/and how reactive the part of the substrate that is accessible to the heme group is. We will review key aspects for various approaches that are available to predict binding and site of metabolism (SOM), what outcome can be expected from the predictions, and how they could potentially be improved.
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Denmark. Electronic address: lo@sund.ku.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Olsen
authors.affiliation: Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, Austria.
authors.forename: Chris
authors.initials: C
authors.lastname: Oostenbrink
authors.affiliation: Department of Drug Design and Pharmacology, University of Copenhagen, Denmark.
authors.forename: Flemming Steen
authors.initials: FS
authors.lastname: Jørgensen
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System
keywords: Cytochrome P450; Docking; Ligand-based models; Machine learning; Molecular dynamics; Reactivity; Site of metabolism; Structure-based models