title: Specific interactions between vitamin-D receptor and its ligands: Ab initio molecular orbital calculations in water.
abstract: Vitamin D is recognized to play important roles not only in the bone metabolism and the regulation of Ca amount in the blood but also in the onset of immunological diseases. These physiological actions caused by vitamin D are triggered by the specific interaction between vitamin D receptor (VDR) and vitamin D. In the present study, we investigated the interactions between VDR and vitamin D derivatives using ab initio molecular simulation, in order to elucidate the reason for the significant difference in their effects on VDR activity. Based on the results simulated, we elucidated which parts of the derivatives and which residues of VDR mainly contribute to the specific binding between VDR and the derivatives at an electronic level. This finding will be helpful for proposing new vitamin D derivatives as a potent modulator or inhibitor against VDR.
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takeda
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580, Japan.
authors.forename: Ittetsu
authors.initials: I
authors.lastname: Kobayashi
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Shimamura
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ishimura
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580, Japan.
authors.forename: Ryushi
authors.initials: R
authors.lastname: Kadoya
authors.affiliation: Drug Research Center, Kaken Pharmaceutical Co. Ltd, 14, Shinomiya, Minamigawara-cho, Yamashina-ku, Kyoto 607-8042, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kawai
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
authors.affiliation: Teijin Institute for Bio-Medical Research, Teijin Pharma Ltd, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Takimoto-Kamimura
authors.affiliation: Department of Computer Science and Engineering, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi, 441-8580, Japan. Electronic address: kurita@cs.tut.ac.jp.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kurita
mesh_terms: D001120:Arginine / Q000737:chemistry; D001665:Binding Sites; D050071:Bone Density Conservation Agents / Q000737:chemistry / Q000378:metabolism*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D003198:Computer Simulation; D030562:Databases, Protein; D004735:Energy Transfer; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D011789:Quantum Theory; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012694:Serine / Q000737:chemistry; D013777:Tetrazoles / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry
chemical_list: D050071:Bone Density Conservation Agents; D008024:Ligands; D018167:Receptors, Calcitriol; D011994:Recombinant Proteins; D013777:Tetrazoles; C579457:VDR protein, human; D014443:Tyrosine; D012694:Serine; D001120:Arginine; D002117:Calcitriol
keywords: Fragment molecular orbital; Inhibitor; Modulator; Molecular simulation; Protein–ligand interactions; Vitamin D receptor