Molecular docking and molecular dynamic simulation of phytochemical derived compounds as potential anti cancer agent against tyrosine kinase

Abstract

There is a continuous requirement to develop novel, safe, effective and affordable anti-cancer drugs because Cancer is a serious disease at current situation. A huge number of patients die annually due to cancer disease.  Phytochemical are the secondary metabolites of medicinal plants and significantly used in conventional cancer research.  Bioactive phytochemical is favored as they claim differentially on cancer cell only without altering normal cell. Carcinogenesis is an intricate process and includes multifold signaling procedures. Phytochemical are pleiotropic in nature, function and target these events in multiple manners so they are considered as most appropriate candidate for drug development. The aim of the present research was to find out the anti-cancer activity of the phytochemical constituents through computer aided drug design approach. In this experiment, we have find total 42 natural compounds with anti-cancer activity against the cancer target 1QCF tyrosine kinase. The data set comprising of phytochemical compounds was used for virtual screening and molecular docking in PyRx software. Along with screened compound, hit compound Carnosic acid was further docked to confirm the binding mode and confirmed the effective inhibition of 1QCF and anticancer activity. Molecular dynamic simulation studies were done to confirm the stability of the protein and ligand complex during a simulation. Parameters like RMSD, RMSF, and radius of gyration were experiential to understand the fluctuations. Protein-ligand interaction studies also expose that enough hydrogen and hydrophobic bonds are present to validate our results. Our study suggests that the potential use of Carnosic acid can come out as a potential candidate and in turn prevent cancer.