Revisiting the inhibitory potential of protein kinase inhibitors against NEK7 protein via comprehensive computational investigations

The NEK7 protein is required for spindle formation, cell division, and the activation of the NLRP3 inflammasome receptor. The aberrant expression of NEK7 has been implicated to the growth of metastasis and severe inflammatory conditions like rheumatoid arthritis, liver cirrhosis, and gout. An emergent target for the development of anti-cancer drugs is NEK7. In this context, the PubChem database was used to retrieve the 675 compound library and FDA-approved protein kinase inhibitors, which were then thoroughly examined via in-silico experiments. Computational studies investigated the binding orientation, electronic, and thermodynamic characteristics of drug candidates related to target protein. Drugs were investigated using density functional theory and molecular docking to find binding interactions with NEK7. Molecular dynamic simulations assessed interactions and stability of protein–ligand complex. DFT analyses showed that selected compounds maintained a significant amount of chemical reactivity in both liquid and gaseous states. Alectinib, Crizotinib, and compound 146476703 all displayed promising molecular interactions, according to molecular docking studies, with docking scores of − 32.76, − 30.54, and − 34.34 kJ/mol, respectively. Additionally, MD simulations determined the stability and dynamic characteristics of the complex over a 200 ns production run. The current study’s findings indicate that the drugs Alectinib, Crizotinib, and compound 146476703 can successfully inhibit the overexpression of the NEK7 protein. To discover more potent drugs against NEK7, it is recommended to synthesize the derivatives of Alectinib and Crizotinib and carry out additional in-vitro and in-vivo studies at the molecular level.