title: In silico prediction of cytochrome P450-mediated site of metabolism (SOM).
abstract: Drug metabolism is a major consideration for modifying drug clearance and also a primary source for drug metabolite- induced toxicity. Cytochromes P450 (CYPs) are the major enzymes involved in drug metabolism and bioactivation, accounting for almost 75% of the total drug metabolism. Predicting the sites of cytochrome P450-mediated metabolism of drug-like molecules using in silico methods would be highly beneficial and time efficient. An ideal system would enable researchers to make a confident elimination decision based purely on the structure of a new compound. In this review, several tools and models for predicting probable site of metabolism (SOM) have been compared and discussed. The methods are generally based on enzyme structure, ligand structure, and combined methods. Although all the methods have certain accuracy and considerable progress has been made, the results of the calculations still need careful inspection.
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.forename: Qiancheng
authors.initials: Q
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Luo
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zheng
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D030562:Databases, Protein; D006801:Humans; D008658:Inactivation, Metabolic; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010084:Oxidation-Reduction; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D008024:Ligands; D003577:Cytochrome P-450 Enzyme System