In silico Based Ligand Design and Docking Studies of GSK-3b Inhibitors

• Published in: Chem-bio informatics journal 2010-01, Vol.10, p.1-12
• Main Authors: Babu, Ajay P, Chitti, Sashikanth, Rajesh, B, Prasanth, Vishnu V, Kishen, Radha JV, Vali, Khadar R
• Format: Article
• Language: English
• Subjects: Free energy
• ISSN: 1347-0442
• DOI: 10.1273/cbij.10.1

Automated docking was performed on a series of thiazolo[5,4-f]quinazolin-9-one derivatives as GSK-3b inhibitors. The docking technique was employed to dock a set of representative compounds within the active site region of 1UV5 using AutoDock 3.05. For these compounds, the correlation between binding free energy (kcal/mol) and IC sub(50) (kM) values were examined. The docking simulation clearly predicted the binding mode that is nearly similar to the crystallographic binding mode within 1.0 Aa RMSD. Based on the validations and interactions made by R1 and R2 substituents, inhibitor design was initiated by considering simple combinations. For the designed compounds where the interactions and dock scores are being considered for evaluation, compound 17 exhibited large binding energy (-13.14 kcal/mol) against GSK-3b than the remaining. The results help to understand the type of interactions that occur between designed ligands with GSK-3b binding site region and explain the importance of R1 and R2 substitutions on thiazolo[5,4-f]quinazolin-9-one derivatives.