Open AccessGLYCOGEN SYNTHASE KINASE-3 BETA PROTEIN INHIBITION BY SELECTED PHYTOCOMPOUNDS IN SILICO
Author(s) -
Vanitha Varadharaj,
Naresh Kandakatl
Publication year - 2016
Publication title -
asian journal of pharmaceutical and clinical research
Language(s) - English
Resource type - Journals
eISSN - 2455-3891
pISSN - 0974-2441
DOI - 10.22159/ajpcr.2017.v10i1.14113
Subject(s) - autodock , docking (animal) , chemistry , hydrogen bond , gsk 3 , lupeol , biochemistry , stereochemistry , in silico , pharmacology , kinase , organic chemistry , biology , molecule , medicine , nursing , gene
Objectives: Bioactive phytocompounds are a rich source of chemopreventive substance. In the present investigation, docking study was performedfor the selected bioactive phytocompounds such as oleanolic acid, ecdysterone, betaine, stigmasterol acetate, and cinnamic acid to evaluate theiraffinity to glycogen synthase kinase-3 beta (GSK-3β) protein, a wound-healing biomarker. 2-chloro-5-[4-(3-chloro-phenyl)-2, 5-dioxo-2,5-dihydro-1hpyrrol-3-ylamino]-benzoicacid wasused as an inhibitorforGSK-3βwith minimum binding energy(−31.5 kcal/mol).Methods: Molecular docking study was conducted using AutoDock 4.2 version and the visualization result using Discover Studio 4.5.Results: The docking analysis ranked the selected phytocompounds that have high theoretical scores to bind to the proteins. The binding mode of thephytocompounds that bound to all the target proteins with high affinity was studied. The simulation demonstrated that the protein-ligand complexstabilized by multiple hydrogen bonds (H-bonds) was preferentially formed at the catalytic site. The results highlighted in this study reveals thatamong the selected lead phytocompounds that docked into the active site of GSK-3β, ecdysterone showed acceptable 6 H-bond interactions withresidues LYS85, TYR134, ARG141, GLN185, ASP200, PRO136 when compared to the reference compound with 5 H-bond interactions.Conclusion: Thus, based on the docking score ecdysterone could be considered as a novel compounds that can be used for experimental studies forthe inhibition of GSK-3β kinase. These results can be helpful for further design of novel GSK-3β inhibitors.Keywords: Phytocompounds, Molecular docking, Simulation, Receptor, Ligand, Inhibition.