Investigations on Binding Pattern of Kinase Inhibitors with PPARγ: Molecular Docking, Molecular Dynamic Simulations, and Free Energy Calculation Studies.
Peroxisome proliferator-activated receptor gamma (PPARγ) is a potential target for the treatment of several disorders. In view of several FDA approved kinase inhibitors, in the current study, we have investigated the interaction of selected kinase inhibitors with PPARγusing computational modeling, docking, and molecular dynamics simulations (MDS). The docked conformations and MDS studies suggest that the selected KIs interact with PPARγin the ligand binding domain (LBD) with high positive predictive values. Hence, we have for the first time shown the plausible binding of KIs in the PPARγligand binding site. The results obtained from these in silico investigations warrant further evaluation of kinase inhibitors as PPARγligands in vitro and in vivo.
Structural Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Mohit
M
Mazumder
Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5C9.
Prija
0000-0002-2643-1947
P
Ponnan
Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5C9.
Umashankar
U
Das
Structural Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Samudrala
S
Gourinath
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
Haseeb Ahmad
0000-0001-6084-8589
HA
Khan
Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5C9.
Jian
0000-0002-4935-7380
J
Yang
Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5C9.
Meena Kishore
0000-0002-9289-3314
MK
Sakharkar