Computational Analysis Depicting Potency of Phytochemicals to Target MAPK Signalling Pathway in Breast Cancer

Abstract

Background: Breast cancer has caused significant mortality among women worldwide. A comprehensive analysis of the disease indicated that MAPK signalling pathways are primarily involved in cell proliferation and have substantially induced drug resistance amongst the diseased individuals and henceforth may be considered a potential drug target to combat the disease. Methods: Phytochemicals obtained from medicinal plants were evaluated for their efficacy to target MAPK by molecular docking and were compared with synthetic analogues available in the market to target the disease. The stability of complexes was determined using MD Simulation, and interaction energy was calculated. Ligand binding pockets of interaction were also depicted along with the computation of RMSD. Results: Withanolide belonging to Withania somnifera exhibited the highest BA at both 35 × 57 × 38 Å and 33 × 41 × 41 Å sites of MAPK. Withanolide showed a BA of -10.2 Kcal/mol in comparison to AL8697 and Ralimetinib mesylate, which represented BA of -8.5 and -8.0 Kcal/mol, respectively. The Withanolide- MAPK complex showed stable conformation during MD Simulation. RMSD value for Withanolide was found to be the least, thereby indicating the least fluctuations during the interactions. Conclusion: The present study unveiled that Withanolide may emerge as a potential drug candidate to target MAPK signalling pathway in breast cancer.