Microbial biomolecule-driven identification of next-gen GSK-3β inhibitors for brain disorders

Health conditions of neurological disorders, including Alzheimer's, schizophrenia, and bipolar disorder, are associated with abnormalities in glycogen synthase kinase-3β (GSK-3β), an essential enzyme that plays a role in neurological growth, neural adaptation, and regulating mood. This research employs an in-silico methodology that utilises molecular docking, ADMET, post-docking MM-GBSA, DFT, MD simulation, post-simulation MM-GBSA, Principal component analysis, and DCCM to identify GSK-3β inhibitors derived from natural products. From 36,395 natural compounds, the top ten with significant GSK-3β binding affinities were identified, and ADMET analysis prioritised three promising molecules: CID_139587391 (NPA015418), CID_11306254 (NPA016078), and CID_57333567 (NPA014273). Each of the compounds interacted with important GSK-3β amino acid residues, such as ALA 83, CYS 199, ILE 62, VAL 70, LEU 188, TYR 134, LEU…