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

Selvaraman Nagamani

doi:10.6026/97320630008705

Abstract

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.

Highlights

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
We collected the have shown that Chronic Kidney Disease (CKD) patients show high level of bone fracture vitamin D receptor (VDR) agonists from the literature and docking analyses were than the normal population and it is increasing with performed with the VDR protein
In summary, a new approach combining molecular docking and pharmacophore filtering have been employed to meet the critical challenges faced in designing efficient VDR agonists to treat calcium phosphate metabolism disorders

Summary

Introduction

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. 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. 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. We collected the have shown that CKD patients show high level of bone fracture VDR agonists from the literature and docking analyses were than the normal population and it is increasing with performed with the VDR protein. Almost 50% of the CKD given as input for E-Pharmacophore mapping Based on this patients undergo dialysis show severe osteoporotic conditions. One way to reduce the incidence of osteoporosis in CKD patients is to stimulate new bone formation [2]

Methods

Findings

Discussion

Conclusion