Atom-based and pharmacophore-based 3D - QSAR studies on Vitamin D Receptor (VDR).

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. The result shows that, AM1 is the good charge model for our study. 3D quantitative structure activity relationship (3D - QSAR) model was generated for 38 Vitamin D analogues and structure and pharmacophore based QSAR was performed. The results revealed that 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. Overall we found that, charge based optimizations of ligands were out performed than the pharmacophore based QSAR model. PMID: 29874993 [PubMed - as supplied by publisher]
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research