Discovery of Novel Lysine Methyltransferase (SMYD3) Inhibitors by Utilizing 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation

To investigate novel isoxazole amide SMYD3 inhibitors as adjuvant anticancer agents for multiple cancers. SET and MYND Domain-Containing Protein 3 is a hopeful therapeutic target for breast, liver, colon, and prostate cancer. Novel SMYD3 inhibitors were predicted by the 3D-QSAR models. In this present work, 3D-QSAR, molecular docking and molecular dynamics (MD) simulations were performed on a series of isoxazole amides-based SMYD3 inhibitors. Molecular docking revealed residues important to protein-compound interactions, indicating that SMYD3 inhibitors have a strong affinity with and bind to key protein residues such as TYR239, MET190, LYS297 and VAL368. The molecular docking results were further validated by molecular dynamics simulations. The above information provided significant guidance for the design of novel SMYD3 inhibitors.