title: Importance of hydrophobic parameters in identifying appropriate pose of CYP substrates in cytochromes.
abstract: Cytochromes are catalytic enzymes which perform oxidative metabolic reactions on drugs. To determine the primary binding forces of CYP-substrate complex, molecular docking studies were carried out. Molecular docking analysis of several drugs with the enzymes CYP2C9, CYP2D6 and CYP3A4 revealed that hydrophobic interactions play a major role in determining the pose selection between substrates and enzymes. GOLD software with hydrophobic and hydrogen bond constraint was employed to identify the specific interactions which play deterministic role in the pose selection.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, Mohali, Punjab 160 062, India.
authors.forename: M
authors.initials: M
authors.lastname: Ramesh
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar, Mohali, Punjab 160 062, India. Electronic address: pvbharatam@niper.ac.in.
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Bharatam
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000737:chemistry / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D012984:Software; D013379:Substrate Specificity
chemical_list: D004364:Pharmaceutical Preparations; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: Cytochromes; Drug metabolism; Hydrophobic interactions; Molecular docking