title: Molecular modeling used to evaluate CYP2C9-dependent metabolism: homology modeling, molecular dynamics and docking simulations.
abstract: Cytochrome P450 (CYP) 2C9 is the principal isoform of the CYP2C subfamily in the human liver and is involved in the oxidation of several endogenous and xenobiotic compounds, including many therapeutic drugs. The metabolism of drugs by CYP2C9 can yield either safe or toxic products, which may be related to the recognition and binding modes of the substrates to this isoform. These interactions can be studied using in silico methods such as quantum chemistry, molecular dynamics and docking simulations, which can also be useful for predicting the structure of metabolites. In these types of studies, the ligand and the protein must be tridimensional models; thus, the protein can be built by homology modeling or retrieved from the Protein Data Bank. Therefore, the current review emphasizes the importance of using in silico methods to predict the metabolism of CYP2C9 because these computational tools have allowed the description of the principal characteristics of the active site of this isoform at the molecular level and the chemical properties of its ligands.
authors.affiliation: Sección de Estudios de Posgrado e Investigación y Departamento de Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Miguel Hidalgo, Distrito Federal, México.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Mendieta-Wejebe
authors.forename: José
authors.initials: J
authors.lastname: Correa-Basurto
authors.forename: Erika M
authors.initials: EM
authors.lastname: García-Segovia
authors.forename: Gisela
authors.initials: G
authors.lastname: Ceballos-Cancino
authors.forename: Martha C
authors.initials: MC
authors.lastname: Rosales-Hernández
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9; D006801:Humans; D008024:Ligands; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011485:Protein Binding
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases