Identification of new inhibitors against human Great wall kinase using in silico approaches

AbstractMicrotubule associated serine/threonine kinase (MASTL) is an important Ser/Thr kinase belonging to the family of AGC kinases. It is the human orthologue of Greatwall kinase (Gwl) that plays a significant role in mitotic progression and cell cycle regulation. Upregulation of MASTL in various cancers and its association with poor patient survival establishes it as an important drug target in cancer therapy. Nevertheless, the target remains unexplored with the paucity of studies focused on identification of inhibitors against MASTL, which emphasizes the relevance of our present study. We explored various drug databases and performed virtual screening of compounds from both natural and synthetic sources. A list of promising compounds displaying high binding characteristics towards MASTL protein is reported. Among the natural compounds, we found a 6-hydroxynaphthalene derivative ZINC85597499 to display best binding energy value of −9.32 kcal/mol. While among synthetic compounds, a thieno-pyrimidinone based tricyclic derivative ZINC53845290 compound exhibited best binding affinity of value −7.85 kcal/mol. MASTL interactions with these two compounds were further explored using molecular dynamics simulations. Altogether, this study identifies potential inhibitors of human Gwl kinase from both natural and synthetic origin and calls for studying these compounds as potential drugs for cancer therapy.