title: Ligand-Based Site of Metabolism Prediction for Cytochrome P450 2D6.
abstract: A ligand-based method based on the SMARTCyp approach that predicts the sites of cytochrome P450 2D6-mediated metabolism of druglike molecules has been developed. The method uses only two descriptors besides the reactivity from SMARTCyp: the distance to a protonated nitrogen atom and the distance to the end of the molecule. Hence, the site of metabolism is predicted directly from the 2D structure of a molecule, without requiring calculation of electronic properties or generation of 3D structures. Testing on an independent test set gives an area under the curve value of 0.94, and a site of metabolism is found among the top two ranked atoms for 91% of the compounds.
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: Lars
authors.initials: L
authors.lastname: Olsen
keywords: CYP2D6; cytochrome P450; drug metabolism