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

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

Volume: 21 Issue: 10

Author(s): YuanZe Shi, XiaoDie Chen, JiaLi Li, Na Yu, JinPing Wu, XueMin Zhao, Mao Shu*ZhiHua Lin

Affiliation:

• School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China

Keywords: 3D-QSAR, molecular docking, molecular dynamics simulation, SMYD3 inhibitors, SET, MYND.

Abstract:

Aims: To investigate novel isoxazole amide SMYD3 inhibitors as adjuvant anticancer agents for multiple cancers.

Background: SET and MYND Domain-Containing Protein 3 is a hopeful therapeutic target for breast, liver, colon, and prostate cancer.

Objective: Novel SMYD3 inhibitors were predicted by the 3D-QSAR models.

Methods: In this present work, 3D-QSAR, molecular docking and molecular dynamics (MD) simulations were performed on a series of isoxazole amides-based SMYD3 inhibitors.

Results: 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.

Conclusion: The above information provided significant guidance for the design of novel SMYD3 inhibitors.

Cite this article as:

Shi YuanZe, Chen XiaoDie, Li JiaLi, Yu Na, Wu JinPing, Zhao XueMin, Shu Mao*, Lin ZhiHua, Discovery of Novel Lysine Methyltransferase (SMYD3) Inhibitors by Utilizing 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation, Letters in Drug Design & Discovery 2024; 21 (10) . https://dx.doi.org/10.2174/1570180820666230419082516