Virtual Screening and Molecular Dynamics Simulation of Natural Compounds as Potential Inhibitors of Serine/Threonine Kinase 16 for Anticancer Drug Discovery

Serine/threonine kinase 16 (STK 16) is involved in many facets of cellular regulation; activation of STK 16 plays a crucial role in the migration of cancer cells. Therefore, it is a novel target for the discovery of anticancer agents. Herein, virtual screeningand dynamics simulation were used to screen a large library of natural compounds against STK 16 using Schrodinger suit 2021-2 and GROMACS 2021.6. The results predicted five molecules with high binding affinity against the target, with NPC 132329 and NPC 160898 having higher binding affinity and molecular mechanics generalized born surface area (MM/GBSA),suggesting that it is better than the standard inhibitor. The MD simulation studies showed that the STK 16-NPC 132329 complex has the lowest root mean square deviation, and STK 16-NPC 160898 was the most stable compared with the standard drug and selective STK 16 inhibitor. The minimal fluctuation was observed in the STK 16-NPC 132329 and STK 16-NPC 160898 complexes based on the root mean square fluctuation trajectory with NPC 132329 and NPC 160898 forming 2 and 3 hydrogen bonds, respectively, with the amino acid residue of the target’s binding site. Overall, NPC 132329 and NPC 160898 are better STK 16 inhibitors than the standard drug and selective inhibitor, which can be further studied to discover novel anticancer drugs.