Rigid and flexible docking studies on PPAR-γ agonists: key interactions for a better antihyperglycemic activity and in silico pharmacodynamic activity versus experimental in vivo activity

Abstract

We report both automated rigid and flexible ligand docking simulations performed on fifty peroxisome proliferator-activated receptor (PPAR-γ) agonists, namely, glitazones. The binding conformations and binding affinities of these agonists were obtained by the use of the Autodock 4.1 with Lamarckian genetic algorithm (LGA). All the 50 flexible docks are considered as well-docked as all of them were bound to the ligand binding domain of PPAR-γ. The predicted binding affinity values (pKa) were found to have some degree of correlation with their experimental in vivo activity values. The head group hydrogen bond interactions via H323 and H449 histidine residues were found to play a significant role. The results obtained will be valuable in designing newer selective PPAR-γ agonists.