Structural exploration of PPARγ modulators through pharmacophore mapping, fragment-based design, docking, and molecular dynamics simulation analyses

摘要: Peroxisome proliferator-activated gamma receptor is an attractive therapeutic target involving various types of metabolic syndrome. Viewing the importance peroxisome modulators, ligand and energetically optimized pharmacophores (e-pharmacophore), hologram-based quantitative structural activity relationships, classification-based Bayesian models were developed, followed by molecular docking, mechanics, dynamic analyses to search for essential requirements in molecules potent selective modulation. Both e-pharmacophore suggest that aromatic ring feature plays crucial role, whereas relationships study indicates phenyl indole rings are scafolds imparting Further, model, dynamics studies depict a carboxyl group modulating agonistic through generating strong H-bonds with active amino acid residues (His323, Tyr327, His449, Tyr473, etc). The multi chemometrics modeling provide some insight into prime features responsible significant property ligands.