IDENTIFICATION OF NOVEL INHIBITORS FOR MITOGEN-ACTIVATED PROTEIN KINASE KINASE 4 BY VIRTUAL SCREENING AND MOLECULAR DYNAMICS SIMULATION TECHNIQUES

Objective: The objective of this study was to discover a therapeutic natural lead compound against mitogen-activated protein kinase kinase 4 (MKK4) employing in silico studies.Methods: In the present study, natural compounds database was first screened for potent inhibitory activity by employing a high throughput virtual screening and molecular docking. The molecular dynamic simulation was used to analyze the stability of ligands.Results: Top ten hit compounds obtained from virtual screening and molecular docking were analyzed for their binding poses. Molecular docking studies reveal that all ten compounds bind into the same binding pocket. Molecular dynamic simulation of ZINC06091752-MKK4 and ZINC00391412-MKK4 complexes revealed stable and potential binding mode of MKK4 to ZINC06091752 and ZINC00391412.Conclusion: The potential binding mode of MKK4 to ZINC06091752 and ZINC00391412 was explored through molecular dynamic simulations. ZINC06091752 and ZINC00391412 have been identified as potential inhibitors of MKK4. Analysis of ligand efficiency profiles through assays would add more value to the current findings and may be beneficial in prostate cancer therapy.Keywords: Molecular Dynamics Simulation, Virtual Screening, Molecular Docking, Prostate Cancer, ERK Kinase-1, MKK