Structure-Based Screening and Molecular Dynamics Simulation Studies for the Identification of Potential Gsk-3β Inhibitors

<p><strong>Abstract</strong></p> <p>The goal of researchers for almost twenty years has been to discover ways to directly block glycogen synthase kinase 3β (GSK3Ų). Structure-based virtual screening (SBVS) and high-throughput enzyme assays were used in order to search through a library of 3,000 compounds in order to identify potential novel GSK3β inhibitors. In comparison to the other compounds, the pyrazolo[1,5-a]pyrimidin-7-amine derivatives stood out owing to their powerful inhibitory action on GSK3β and their noteworthy modification of Wnt signaling pathways. The subsequent SBVS was directed by molecular dynamics (MD) simulations that were supplemented with upper-wall limitations. These simulations assisted in the refinement of the structural understanding of ligand binding. Through the use of this integrated strategy, the identification of highly effective and selective GSK3β inhibitors, as well as the acquisition of extensive knowledge on their binding mechanisms, became feasible. The findings of this research have the potential to provide the foundation for the enhancement of potential therapeutic medicines that target GSK3β within the hunt for viable therapeutic agents.</p> <p><strong>Keywords:</strong> GSK-3β inhibitors, Structure-based virtual screening (SBVS), Molecular dynamics (MD) simulation, Enzyme inhibition</p>