E-Pharmacophore mapping and docking studies on Vitamin D receptor (VDR).
Small structured chemical molecules are importance in the field of molecular medicine since their pharmacokinetic and pharmacodynamic properties are predictable and because of its ability to bind with target molecules and execute biological function. In this study, we engaged computer-aided methodology in combination with molecular docking and pharmacophore filtering to identify chemical compounds that can increase the synthesis of vitamin D receptor (VDR) since its lower expression leads to calcium phosphate metabolic disorders in Chronic Kidney Disease. Energy-optimized pharmacophore was mapped using available agonists for VDR. Based on the e-pharmacophore, we propose the pharmacophore features that should present in VDR agonists. The resulting pharmacophore model contains one hydrogen bond acceptor (A), one hydrogen bond donor (D) and two hydrophobic regions (H). Using these features pharmacophore had been made and screened against large public library of compounds (Asinex, TOSLab, Binding and Zinc database) to find potential lead compounds. The compounds which yield fitness score 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 metabolic disorders.
Department of Bioinformatics, Alagappa University, Karaikudi 630 004, India.
Selvaraman
S
Nagamani
Chandrasekhar
C
Kesavan
Karthikeyan
K
Muthusamy