Investigation of Plant-Derived Compounds as Potent Inhibitors of Casein Kinase-1 Alpha through Computational Analysis and Molecular Dynamic Simulations

Casein kinase-1 alpha (CK1α) is a kinase family enzyme involved in a number of key cell-signalling pathways, such as Wnt/β-catenin, p53, and circadian rhythm. CK1α overexpression and dysregulation are linked to a number of pathogeneses, including neurodegeneration, cancer and inflammatory diseases. In this investigation, computational methods have been applied to discover the potential scaffolds as CK1α inhibitors from the database. We evaluated the binding affinity of selected phytoconstituents from the IMPPAT database using molecular docking and molecular dynamics (MD) simulations. Significant candidates targeting CK1α were identified based on their docking score and binding interactions. The ADMET assessment was conducted to identify potent drug-like candidates with promising pharmacokinetic behaviours. Among the screened compounds, Ochrolifuanine A ( -11.1 kcal/mol) and Trichotomine ( -10.6 kcal/mol) are exhibited superior binding affinities as compared to the standard ligand Liriodenine (-10.1 kcal/mol) . Blind docking was applied for further confirmation of the robust interaction characteristics of the compounds. The docking complexes were analysed by MD simulations, and were statistically evaluated using RMSD value, RMSF analysis, radius of gyration (Rg) values, and SASA analysis (solvent accessible surface area), demonstrating the structural compactness and binding affinity of the protein-ligand complexes over time. These outcomes suggest that the identified phytochemical constituents have promising potential as CK1α inhibitors and need more experimental proof for developing new chemical entities.