36
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Ligand-dependent conformation change reflects steric structure and interactions of a vitamin D receptor/ligand complex: a fragment molecular orbital study.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          We used an in silico computational method to theoretically analyze important residue-ligand interactions as well as ligand conformation changes in the vitamin D receptor (VDR). The ligand used for analysis was 1alpha,25-dihydroxy-19-nor-vitamin D3 [1alpha,25-19-nor-(OH)2D3] [1,2], whose crystal structure has not been solved. To estimate amino acid residue-ligand interactions with chemical accuracy, we adopted the fragment molecular orbital (FMO) method [3,4], which is based on the nonempirical total electronic quantum calculation. The docking of the ligand to the VDR was controlled by hydrophilic and hydrophobic interactions between amino acid residues and the ligand in the ligand binding pocket (LBP) [5-8]. These molecular interactions changed when the conformation of the ligand in the VDR was changed [5,9,10]. This conformation change is important to consider in computational, in silico, approaches for analyzing the mechanism of ligand-docking to the VDR. The position of the 1alpha,25-19-nor-(OH)2D3 ligand in the VDR-LBP was related to the hydrophobic interaction that occurred between the Ile271 residue of the VDR-LBP and the ligand. The interaction between Ile271 and 1alpha,25-19-nor-(OH)2D3 was repulsive, whereas, that between Ile271 and the natural ligand, 1alpha,25-(OH)2D3, is stable. The orientation change in the isopropyl group of Ile271 affected the residue's interaction with 1alpha,25-19-nor-(OH)2D3. We also found that conformation changes in the A-ring affected electrostatic (hydrophilic) interactions between the VDR and the ligand.

          Related collections

          Author and article information

          Journal
          J. Steroid Biochem. Mol. Biol.
          The Journal of steroid biochemistry and molecular biology
          Elsevier BV
          1879-1220
          0960-0760
          Jul 2010
          : 121
          : 1-2
          Affiliations
          [1 ] Department of Chemistry, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan.
          Article
          S0960-0760(10)00115-9
          10.1016/j.jsbmb.2010.03.024
          20236615
          c1dff246-4b1c-4a9f-b872-7a19ec99c6ef
          History

          Comments

          Comment on this article