In silico Study on the Active Site Conformation and Structural Modulation of Glycerol-3-Phosphate Acyltransferase in Relevance to Medicinal SignificanceDownload PDF
Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the first step in the synthesis of glycerolipid and glycerophospholipids.Overexpression of GPAT can lead to certain diseases like atherosclerosis and by extension, the risk of heart disease, stroke, obesity and hypertension. The present study was designed to develop specific analogues having high binding affinity for the receptor, probably helping in controlling the overexpression of triacylglycerol (TG) by molecular docking using Vlife MDS. To study the molecular interaction the receptor was docked with GPAT isomers 1IUQ &1K30 after energy minimization. The results obtained after docking indicated formation of a stable complex with strong binding affinity. It was also observed that the amino acid residues involved in this interaction and the predicted residues responsible for binding are GLU124, TYR158, ILE159, ALA160, ASP162, THR163, LEU177 & LEU226 and PRO238, GLY243, TRY245, LYS246, HIS279, ASP280, PRO283, GLU294, ARG296 & ALN299.The molecular interaction between GPAT and its receptor provides new insights into the elucidation of structural domains and development of functional analogues with higher binding affinity and new drug combination therapies for the treatment of obesity.
Keywords: GPAT, Inhibitor designing, Molecular docking, Obesity, TG, Vlife MDS.