An In Silico Study to Explore the Role of EGFR in Ovarian Cancer

Abstract

The EGFR family of Receptor Tyrosine Kinases (RTKs) consists of 4 members (collectively referred to as the ErbB or HER family): EGFR itself, ErbB2 (HER2/Neu), ErbB3 (HER3) and ErbB4 (HER4). Like all RTKs, each ErbB receptor comprises a large extracellular region, a single spanning trans-membrane (TM) domain, an intracellular ABSTRACT EGFR is a tyrosine kinase receptor that has a role in the tumorigenesis of many types of solid tumors. Aberrantly phosphorylated or overexpressed EGFR is associated with cellular proliferation, prevention of apoptosis, activation of invasion and metastasis, and stimulation of tumor-induced neovascularization. EGFR's hyperactivity has been observed in ovarian cancer. Although conventional chemotherapy and surgery for advanced ovarian cancer have improved over the years, still there is a critical need for the development of molecular targeted therapies. The major challenge for this approach is the complete understanding of the protein structure of this mega receptor. In this study, we explored this receptor using in silico tools. The protein structure of the EGFR kinase domain (PDB ID: 1M17) and co-crystal containing EGFR and PTP1B kinase domain fragment (PDB ID: 3I7Z) were obtained from the RCSB Protein Data Bank. We performed protein-protein docking using BioLuminate. It was found in this study that the DADEYL segment of EGFR (position 988-993) which includes autophosphorylated tyrosine at position 992, is the segment that is responsible for the overexpression of this receptor in ovarian cancer. There are currently two main classes of clinically-approved drugs which downregulate EGFR activity; tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (Mabs). However, treatment with both type of therapies has been met with shortcomings. Therefore, there is a need for further studies to explore the suitable ligands that can downregulate its activity.

In Silico Analysis of Protein–Protein Interactions of Putative Endoplasmic Reticulum Metallopeptidase 1 in Schizosaccharomyces pombe

“…Finally, ClusPro 2.0 and BioLuminate 4.5 are molecular-docking tools that have been widely utilized in diverse biological systems due to their automated computational system and the quality of the predictions, which exceed 50% of the success rate compared to other tools [122][123][124][125]. Since the predictions in both programs were similar, it can be suggested that they are congruent; however, other tools could be used to confirm the results.…”