title: SMARTCyp: A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism.
abstract: SMARTCyp is an in silico method that predicts the sites of cytochrome P450-mediated metabolism of druglike molecules. The method is foremost a reactivity model, and as such, it shows a preference for predicting sites that are metabolized by the cytochrome P450 3A4 isoform. SMARTCyp predicts the site of metabolism directly from the 2D structure of a molecule, without requiring calculation of electronic properties or generation of 3D structures. This is a major advantage, because it makes SMARTCyp very fast. Other advantages are that experimental data are not a prerequisite to create the model, and it can easily be integrated with other methods to create models for other cytochrome P450 isoforms. Benchmarking tests on a database of 394 3A4 substrates show that SMARTCyp successfully identifies at least one metabolic site in the top two ranked positions 76% of the time. SMARTCyp is available for download at http://www.farma.ku.dk/p450.
authors.affiliation: Biostructural Research, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Patrik
authors.initials: P
authors.lastname: Rydberg
authors.affiliation: Biostructural Research, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: David E
authors.initials: DE
authors.lastname: Gloriam
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York 12180.
authors.forename: Jed
authors.initials: J
authors.lastname: Zaretzki
authors.affiliation: Center for Biotechnology and Interdisciplinary Studies, Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, New York 12180.
authors.forename: Curt
authors.initials: C
authors.lastname: Breneman
authors.affiliation: Biostructural Research, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Olsen
keywords: Cytochromes P450; DFT; density functional theory; heme; metabolism