E-Pharmacophore mapping and docking studies on Vitamin D receptor (VDR)

Abstract

Small structured chemical molecules are importance in the field of molecular medicine since their pharmacokinetic andpharmacodynamic properties are predictable and because of its ability to bind with target molecules and execute biologicalfunction. In this study, we engaged computer-aided methodology in combination with molecular docking and pharmacophorefiltering to identify chemical compounds that can increase the synthesis of vitamin D receptor (VDR) since its lower expressionleads to calcium phosphate metabolic disorders in Chronic Kidney Disease. Energy-optimized pharmacophore was mapped usingavailable agonists for VDR. Based on the e-pharmacophore, we propose the pharmacophore features that should present in VDRagonists. The resulting pharmacophore model contains one hydrogen bond acceptor (A), one hydrogen bond donor (D) and twohydrophobic regions (H). Using these features pharmacophore had been made and screened against large public library ofcompounds (Asinex, TOSLab, Binding and Zinc database) to find potential lead compounds. The compounds which yield fitnessscore of more than 1.0 were further subjected to Glide HTVS, SP and XP. Glide docking results revealed five hits (BD_230,BD_12938, BD_18601, BD_19517 and BD_19584) were identified as potential lead molecules against calcium phosphate metabolicdisorders.