Proteomics Analysis of MSH2 Protein and Molecular Docking Approach for Colorectal Cancer Targeted therapy

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, with a diverse genetic profile. CRC is the outcome of a gradual accumulation of genetic and epigenetic changes, resulting in significant genomic instability. The present treatment procedures include surgery/polypectomy, chemotherapy, radiotherapy, combination therapy, and immunotherapy, while advanced methods include gene therapy, cellular therapy, and targeted immunotherapy which is in the emerging phase. Understanding the molecular mechanisms underlying CRC is crucial for developing effective diagnostic, prognostic and therapeutic strategies. Integrating Next Generation Sequencing (NGS) and proteomics data provides a comprehensive view of the molecular alterations in CRC. In the present study, the expression levels of MSH2/MSH6 genes and their proteomic analysis of MSH2 protein were carried that offers valuable insights into their role in CRC. Interactive views of the 3D structure of MSH2 was analysed, revealing sequence-structure relationships, and bound ligands, which are critical for understanding the functional implications of MSH2 alterations. Molecular docking studies highlighted potential therapeutic targets by performing interactions with potent ligands like Bevacizumab,                      a monoclonal antibody that targets the vascular endothelial growth factor (VEGF) and Tucatinib, a tyrosine kinase inhibitor drug. The docking results support the efficacy of targeted therapy of Bevacizumab and Tucatinib in CRC. These findings underscore the potential for early detection, genetic analysis, and computational approaches to drive forward colorectal cancer research and improve patient outcomes. Targeting MSH2, either through restoration or modulation, offers a promising therapeutic strategy. Further investigations and clinical trials are necessary to validate the efficacy of identified ligands and explore their therapeutic potential in treating colorectal cancer.