IN SILICO EXPLORATION OF MARCH2 PROTEIN: A SHARED E3 LIGASE IN NEURODEGENERATIVE DISEASES AND CANCER

Abstract

Aim: This study showcases an in-depth investigation into E3 ligases implicated in neurodegenerative diseases (NDDs) and cancer. It involved a comprehensive literature survey, structural studies, and molecular docking simulations (MDS) analysis with a particular focus on the MARCH2 protein. Background: The literature review unravelled common E3 ligases in NDDs and cancer, highlighting their importance as common therapeutic targets. Among the common E3 ligases, the MARCH2 protein is documented to be overexpressed in colorectal cancer. It also showcases a regulatory function in CFTR-mediated autophagy shedding light on its relevance in NDDs. These instances highlight its significance in the mechanisms underlying cancer and NDDs. Methodology: An in-depth structural analysis was conducted using the SWISS model of the RING domain to determine the structural features and therapeutic importance of the MARCH2 protein. Subsequently, MDS studies were performed using EasyDock Vina and CHARMM-GUI to predict the interaction of MARCH2 with drugs from DrugBank and Phytochemica, providing insights into potential therapeutic interventions. Results: The MDS studies yielded promising results, highlighting the stability of the MARCH2-Tafluposide and MARCH2-Ergotamine complexes. The results of this project suggest that targeting MARCH2 could be a promising strategy for curing cancer and lays a strong foundation for understanding the common molecular mechanisms involving E3 ligases in both NDDs as well as cancer [1]. Additionally, it paves the way for precision medicine by rendering insights into the development of novel strategies that target the MARCH2 protein.