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 |
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Authors: | B R Prashantha Kumar S Sopna Jenson Verghese Bijoy Desai M J Nanjan |
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Institution: | 1. Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Ootacamund, 643001, India 2. TIFAC CORE, JSS College of Pharmacy, Ootacamund, 643001, India
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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. |
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