Abstract

COMPUTATIONAL DRUG DISCOVERY OF POTENTIAL GLUCOKINASE SENSITIZER USE BY INSILICO STUDIES

Dr. Mrityunjay Banerjee*, Rasmi Ranjan Biswakarma, Sahin Meheboob, Sujit Kumar Sahu

ABSTRACT

Glucokinase is expressed in multiple organs & play a key role in heapatic glucose metabolism & pancreatic insulin secretion. Glucokinase could indeed serve as pacemaker of glycolysis & could be an attractive target for type-2 diabetes. the recent preclinical data of first GK activator RO-28-1675 has opened up a new field of GK activation as a powerful tool in T2D therapies, The GK allosteric site is located 20A away from glucose binding site. chemical structure of the Glucokinase activator includes three chemical arms, all consisting of cyclic moiety & joined in a shape resembling the letter Y. The current study was designed to identify suitable agents for Glucokinase. Computer-assisted molecular modeling approach has contributed to the successful discovery of several novel antidiabetic Glucokinase agents by docking-based virtual screening method. Glibenclamide, Glipizide, Glimipiride, Gliclazide are the approved and marketed drug. Protein-ligand interactions were studied using Glucokinase protein PDB ID 1V4S, obtained from Protein data bank to evaluate the affinity of various Glucokinase modulating analogues towards ligand binding site and to study the extent of correlation between experimental values and computational dock scores, to proposed a new compounds (RPM4) with Glibenclamide, Glipizide, Glimipiride, Gliclazide as the standard. Molecular docking using Hex 5.1 and MVD suggests the importance of evaluating the prediction accuracy of studied Glucokinase modulating synthetic analogues. The resulting data of receptor-ligand interactions demonstrates that in silico screening method is highly efficient for identifying potential lead compounds against major disorders/diseases.

Keywords: Antidiabetic, Docking, Hex 5.1, MVD 5.5. Argus lab. Diabetes mellitus Type 2.