Comparison of AutoDock and Glide towards the Discovery of PPAR Agonists

Peroxisome Proliferator Activated Receptors are lipid-sensors and regulate energy metabolism. The agonists of PPARs are of interest to the pharmaceutical industry since they regulate the expression of genes associated with diseases like cancer, diabetes, atherosclerosis and obesity. Synthetic agonists are more likely to cause side effects. Hence eight naturally occuring lipid ligands (tocotrienol α , β , γ and δ , DHA, EPA, 2-Arachidonyl Glycerol and Anandamide) were tested for their ability to act as the agonists of PPARs. DHA and EPA were identified as the dual agonists of PPAR α and γ. DHA and EPA have beneficial health effects in the treatment of cancer, obesity and inflammatory diseases. Two different docking methods Autodock and Glide were performed to compare their suitability for PPARs. Interestingly in both the docking programs the ligands have occupied the same binding pocket confirming the selection of active site. Autodock yielded better results than Glide for PPAR α and γ whereas the performance of Glide was better in case of PPAR δ . --4th International Conference on Bioscience, Biochemistry and Bioinformatics held: Mercure Melbourne Treasury Gardens, Melbourne, 4-5 January, 2014