title: Exploration of the binding of curcumin analogues to human P450 2C9 based on docking and molecular dynamics simulation.
abstract: Molecular docking and molecular dynamics (MD) simulations are used to investigate the interactions of curcumin analogues (CAs) with human cytochrome P450 2 C9 (CYP2C9 or 2 C9) and the conformations of their binding sites. In order to examine conformations of CAs/2 C9 and interaction characteristics of their binding sites, RMSDs, RMSFs, and B-factors are computed, and electrostatic and hydrophobic interactions between CAs and 2 C9 are analyzed and discussed. Results demonstrate that the most CAs studied lie 4~15 Å above the heme of CYP2C9. The presence of CAs makes some residues in bound CYP2C9s become more flexible. In the binding sites of A0/2 C9 and C0/2 C9, the formation of H-bond networks (or CA-water-residue bridges) enhances the interactions between CAs and 2 C9. The stronger inhibitory effects of A0, B0, and C0 on 2 C9 can be ascribed to stronger electrostatic and hydrophobic interactions in the binding sites of CAs/2 C9.
authors.affiliation: State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemistry and Chemical Engineering, Nanjing University of Technology, Nanjing, China.
authors.forename: Rongwei
authors.initials: R
authors.lastname: Shi
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Lu
mesh_terms: D020816:Amino Acid Motifs; D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry*; D001665:Binding Sites; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry*; D065729:Cytochrome P-450 CYP2C9; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006418:Heme / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D014867:Water; D006418:Heme; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D003474:Curcumin
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