Atom-based and Pharmacophore-based 3D – QSAR Studies on Vitamin D Receptor (VDR)

Author(s): Selvaraman Nagamani, Chandrasekhar Kesavan, Karthikeyan Muthusamy*

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 21 , Issue 5 , 2018

Become EABM
Become Reviewer
Call for Editor


Aim and Objective: Vitamin D3 (1,25(OH)2D3) is a biologically active metabolite and plays a wide variety of regulatory functions in human systems. Currently, several Vitamin D analogues have been synthesized and tested against VDR (Vitamin D Receptor). Electrostatic potential methods are greatly influence the structure-based drug discovery. In this study, ab inito (DFT, HF, LMP2) and semi-empirical (RM1, AM1, PM3, MNDO, MNDO/d) charges were examined on the basis of their concert in predicting the docking pose using Induced Fit Docking (IFD) and binding free energy calculations against the VDR.

Materials and Methods: Initially, we applied ab initio and semi-empirical charges to the 38 vitamin D analogues. Further, the charged analogues have been docked in the VDR active site. We generated the structure-based 3D-QSAR from the docked conformation of vitamin D analogues. On the other hand, we performed pharmacophore-based 3D-QSAR.

Results: The result shows that, AM1 is the good charge model for our study and AM1 charge based QSAR produced more accurate ligand poses. Furthermore, the hydroxyl group in the side chain of vitamin D analogues played an important role in the VDR antagonistic activity.

Conclusion: Overall, we found that charge-based optimizations of ligands were out performed than the pharmacophore based QSAR model.

Keywords: Vitamin D receptor, 3D-QSAR, empirical and semi-empirical calculations, AM1, induced fit docking, vitamin D analogues.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2018
Published on: 20 July, 2018
Page: [329 - 343]
Pages: 15
DOI: 10.2174/1386207321666180607101720
Price: $65

Article Metrics

PDF: 38