Molecular Docking and Simulation Studies of FDA Approved Drugs Targeting Allosteric Inhibition of Glycogen Synthase Kinase-3β

Background: Inhibition of glycogen synthase kinase (GSK-3β) by various mechanisms of inhibition has become an important drug target for treating neurodegenerative diseases such as Alzheimer’s disease (AD). AD is characterized by cognitive, memory loss, and behavioral impairments. The pathological hallmarks of AD which appear before the clinical symptoms are neurofibrillary tangles and amyloid plaques. Aim and Objectives: In the present study, we focused on the in-silico-based prediction approach for the virtual screening of FDA-approved ligands (Drug bank database) to target the allosteric pocket of GSK-3β, with the help of Schrodinger (Maestro software). Results and Conclusion: After various levels of screening compounds, out of 2133 FDA-approved ligands, only three compounds formoterol, salmeterol, and polydatin were subjected to induced fit docking (IFD). After performing IFD, one top pose of the above three compounds was proposed for molecular dynamics studies by using the Desmond module. Formoterol showed the most stable interactions with the key amino acid residues. However, further to confirm these finding experimental studies are required.