title: Binding mode pediction of evodiamine within vanilloid receptor TRPV1.
abstract: Accurate assessment of the potential binding mode of drugs is crucial to computer-aided drug design paradigms. It has been reported that evodiamine acts as an agonist of the vanilloid receptor Transient receptor potential vanilloid-1 (TRPV1). However, the precise interaction between evodiamine and TRPV1 was still not fully understood. In this perspective, the homology models of TRPV1 were generated using the crystal structure of the voltage-dependent shaker family K(+) channel as a template. We then performed docking and molecular dynamics simulation to gain a better understanding of the probable binding modes of evodiamine within the TRPV1 binding pocket. There are no significant interspecies differences in evodiamine binding in rat, human and rabbit TRPV1 models. Pharmacophore modeling further provided confidence for the validity of the docking studies. This study is the first to shed light on the structural determinants required for the interaction between TRPV1 and evodiamine, and gives new suggestions for the rational design of novel TRPV1 ligands.
authors.affiliation: State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.|The First Affiliated Hospital, Baotou Medical College, Baotou 014010, China.
authors.forename: Zhanli
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Lidan
authors.initials: L
authors.lastname: Sun
authors.affiliation: The Second Affiliated Hospital, Baotou Medical College, Baotou 014010, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: The First Affiliated Hospital, Baotou Medical College, Baotou 014010, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The First Affiliated Hospital, Baotou Medical College, Baotou 014010, China.
authors.forename: Wuzhuang
authors.initials: W
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Liangren
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Trauma, Burns, and Combined Injury, Department 1, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Liang
mesh_terms: D000818:Animals; D001665:Binding Sites; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011799:Quinazolines / Q000737:chemistry* / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011799:Quinazolines; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C493922:Trpv1 protein, rat; C049639:evodiamine