Molecular docking study on vitamin D supplements to understand their interaction with VDR-RXRα heterodimer and VDRE of TAGAP gene

Abstract

The expression level of T cell activation Rho GTPase activating protein (TAGAP) gene is higher in rheumatoid arthritis (RA) patients compared to healthy individuals. Vitamin D receptor element (VDRE) sequences present in the regulatory region of TAGAP gene are targeted by vitamin D dependent Vitamin D receptor (VDR) - retinoic acid X receptor (RXR) heterodimer complex to regulate the TAGAP gene expression. Reduction in the expression of the TAGAP gene can prevent different severity of RA disease conditions. Calcitriol is a proven vitamin D supplement prescribed to patients with RA. However, it is involved in causing hypercalcemia. Maxacalcitol, an analog of vitamin D, is shown to have less hypercalcemic activity when compared to calcitriol. This study was done to analyze and compare the binding modes of calcitriol and maxacalcitol with VDR. We also studied the interactions of these compounds with the VDR-RXRα heterodimer complex. In addition, the binding of the ligand-activated heterodimer complexes with VDREs of the TAGAP gene was also analyzed to comprehend the binding affinities of calcitriol and maxacalcitol to the gene. The current work utilizes in silico molecular docking and simulation analysis to understand the mechanism in each complex formation.

Communicated by Ramaswamy H. Sarma

Keywords:

• Rheumatoid arthritis
• hypercalcemia
• calcitriol
• maxacalcitol
• TAGAP
• VDRE

Acknowledgements

The authors are thankful to Vellore Institute of Technology, Vellore, Tamil Nadu, for providing support and infrastructural facilities to carry out this study.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.