Screening the binding potential of quercetin with parallel, antiparallel and mixed G-quadruplexes of human telomere and cancer protooncogenes using molecular docking approach

Abstract

The bioinformatics analysis revealed that more than 400,000 DNA sequences within the human genome have the potential of forming G-quadruplex structures. Specifically, G-quadruplexes have been proved to be involved in the regulation of replication, DNA damage repair, transcription and translation of cancer-related genes and hence a therapeutic target. Targeting G4 with small molecules may regulate its expression. Chemical molecules generally shows more cellular toxicity while natural small molecules are more bioavailable and hence shows high biological activity together with low toxicity. In the present study, we have screened the binding potential of quercetin with parallel, anti-parallel and mixed conformations of telomeric G-quadruplexes, cancer protoncogenes and RNA G-quadruplex using molecular docking approach. Our results suggest that the quercetin mainly binds with grooves of all selected G-quadruplxes and its planer aromatic rings stabilizes the structure by π-π stacking. The binding energies were in a range of − 40.24 to − 17.11 kcal/mol, − 35.73 to − 18.09 kcal/mol, − 32.68 to − 22.47 kcal/mol for telomeric parallel, anti-parallel and mixed G-quadruplexes respectively. Further, binding energies of quercetin with selected cancer proto-oncogenes are in a range of − 38.67 to − 12.95 kcal/mol and − 14.8 and − 14.6 kcal/mol for selected RNA G-quadruplex. Hence, this study highlights the comparative differences in binding energies of quercetin even with a group of single conformation of G-quadruplex and helpful to evaluate the binding potential of quercetin to inhibit the activity of telomerases and down-regulate the expression of oncogenes and to be used as a potential anti-cancer agent.