A computational approach to determine susceptibility to cancer by evaluating the deleterious effect of nsSNP in XRCC1 gene on binding interaction of XRCC1 protein with ligase III

• SNP rs2307166 of XRCC1 protein is predicted to be the most damaging nsSNP.
• Analyses of deleterious effect of SNP on protein structure and functionality
• Docking analysis to study the impact of rs2307166 on XRCC1-LIG3 interactions

Several reports suggest that non-synonymous single nucleotide polymorphisms affect the function of XRCC1 which impairs DNA repair capacity and thus increases risk to diseases like cancer. In our study, we predicted the most damaging nsSNPs using a computational approach and analysed its functional impact on the XRCC1 and LIG3 interaction. SNP rs2307166 was predicted to be deleterious using eight software programs: SIFT, PolyPhen, PANTHER, PhD-SNP, nsSNPAnalyzer, SNPS&GO, SNAP and I-Mutant. Protein structural analysis was performed using Swiss PDB viewer, and PyMOL. Xenoview was used for molecular dynamic simulation and energy minimisation. Finally, PatchDock and FireDock were used to analyse the interactions of XRCC1 and LIG3. By comparing the results we found that the mutant protein has less binding energy and the interacting amino acids than native protein. In silico analysis predicted rs2307166 to be more damaging than three other extensively studied SNPs. Identification of this SNP will help in determining the susceptibility of the individual to cancer, their prognosis and further treatment.