Epicatechin as a potential hit to target ERK2 in breast cancer: molecular docking, molecular dynamic simulation studies

Abstract

Breast cancer is the most prevalent cancer globally, leading to significant mortality rates. Despite advancements in treatment modalities, including chemotherapy, surgery, radiotherapy, hormonal therapy, and targeted therapy, issues such as adverse effects and intricate signaling pathways necessitate the development of novel and safer therapeutic options. Overexpression of the ERK2 protein of the MAPK/ERK pathway has a significant role in breast cancer progression by modulating cell proliferation, survival, and apoptosis. Our study involved the screening of a library of 241 phytochemicals for their inhibitory potential against ERK2 using molecular docking, molecular dynamics simulations, binding free energies, etc. Epicatechin emerged as a promising candidate having a docking score of -10.847 kcal/mol better than the control (docking score of -9.719 kcal/mol) and also had better conformational stability as shown by molecular dynamics simulation. These preliminary findings suggest that epicatechin, through its ERK2 inhibition, could serve as a valuable addition to breast cancer therapy, warranting further investigation and clinical validation.