Specific interactions between vitamin-D receptor and its ligands: Ab initio molecular orbital calculations in water

J Steroid Biochem Mol Biol. 2017 Jul;171:75-79. doi: 10.1016/j.jsbmb.2017.02.018. Epub 2017 Feb 27.


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.

Keywords: Fragment molecular orbital; Inhibitor; Modulator; Molecular simulation; Protein–ligand interactions; Vitamin D receptor.

Publication types

  • Comparative Study

MeSH terms

  • Arginine / chemistry
  • Binding Sites
  • Bone Density Conservation Agents / chemistry
  • Bone Density Conservation Agents / metabolism*
  • Calcitriol / analogs & derivatives*
  • Calcitriol / chemistry
  • Calcitriol / metabolism
  • Computer Simulation
  • Databases, Protein
  • Energy Transfer
  • Humans
  • Isomerism
  • Kinetics
  • Ligands
  • Models, Molecular*
  • Molecular Conformation
  • Protein Conformation
  • Quantum Theory
  • Receptors, Calcitriol / agonists*
  • Receptors, Calcitriol / chemistry
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Serine / chemistry
  • Tetrazoles / chemistry
  • Tetrazoles / metabolism*
  • Tyrosine / chemistry


  • Bone Density Conservation Agents
  • Ligands
  • Receptors, Calcitriol
  • Recombinant Proteins
  • Tetrazoles
  • VDR protein, human
  • Tyrosine
  • Serine
  • Arginine
  • Calcitriol