In silico Characterization of Rad51a Interactions with Cancer-Related Proteins

Abstract

RAD51a is a highly conserved protein and its major role is the repair of DNA double strand breaks. Endogenous species are generated during normal cell metabolic activities and can cause damage to DNA, as well as several environmental factors. The interactions RAD51a perform with other proteins help the maintenance of oncogenetic metabolism within cells. RAD51a interacts with PCNA, FANCD2 and ABL1, among many other cancer-related proteins. PCNA acts as a DNA clamp and is related to the replication process, FANCD2 arrests DNA replication fork progression in response to DNA damage and ABL1 is a proto-oncogene related to cell differentiation. Protein-protein interactions (PPIs) are governed by the presence of hot spots within the interface of interaction. Identifying residues directly involved in PPIs enables the likelihood of modulating such complexes with biologically active small molecules such as synthetic peptides, which leads to a new era of diseases treatment. Here, we use an in silico approach to determine the best free-energy of interaction between RAD51a and the targeted cancer-related proteins PCNA, FANCD2 and two chains of ABL1. We propose an interaction interface between RAD51a and those proteins and identified hot spots that could be useful to understand the molecular basis of their interaction. We believe that further studies may find small-targeted molecules with therapeutics properties that could modulate those interactions and increase our knowledge regarding the complex trait diseases such as cancer.