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

•We investigated specific interactions between vitamin D receptor (VDR) and its ligand.•Electronic states were calculated using ab initio fragment molecular orbital method.•The tetrazole ring of the ligand-1 contributes to the CH-π interactions with VDR.•The difference in the ring structure causes a significant difference in binding with VDR.•Arg274 and Ser278 of VDR interact strongly with the ligands.

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.

Graphical abstractInteracting structures between VDR residues (Tyr143, Ser237, and Hid305) and ligand 1. Green lines and a red line indicate hydrogen bonding and CH-π interactions between the residue and ligand 1, respectively.Download high-res image (101KB)Download full-size image