Molecular docking studies of guggultetrol from Nymphaea pubescens with target glucokinase (GK) related to type-II Diabetes

Abstract

Article history: Received on: 07/12/2012 Revised on: 31/12/2012 Accepted on: 07/02/2013 Available online: 28/02/2013 Diabetes prevalence is one of the life threatening diseases in India. In this work we address a specific suitable ligand for diabetes mellitus. A large focus has been on structure based drug designing. Guggultetrol isolated from Nymphaea pubescenswas taken as ligand for molecular docking. A theoretical docking study, the evaluation of guggultetrol as inhibitor of Glucokinase (PDB ID: 1V4S) a validated drug target enzyme of the Type-II diabetes, was taken up. Guggultetrol was found to bind at active site of glucokinase with lowest binding energy and RMSD values to be -9.45Kcal/Mol and 2.0 A respectively. Docking analysis of 1V4S with ligand enabled us to identify specific residues viz. Thr-168, Glu-290, Glu-51, Ser-411, Gly-410, Asn-254, Thr-206, Arg-155 and Asp-205 within the 1V4S binding pocket to play an important role in ligand binding affinity. The docking studies of the Guggultetrol with target protein showed that this is a suitable molecule which docks well with target related to diabetes mellitus. This compound has shown promising biological activity in preliminary studies by targeting multiple signaling pathways. Thus on the basis of our in silico studies we hypothesize that this compound into guggultetrol can be inhibitory effect on against diabetes. We concluded that the natural products with interesting biological properties and structural diversity have often served as valuable lead drug candidates for the treatment of human diseases.