Mohadeseh Bazoobandi, Mohammad R. Bozorgmehr*, Ali Mahmoudi and Ali Morsali Pages 546 - 554 ( 9 )
Aim and Objective: The stability of the G-quadruplex structure can increase its activity in telomerase inhibiting cancer cells. In this study, a molecular dynamics simulation method was used to study the effect of three phenanthroline-based ligands on the structure of G-quadruplex at the temperatures of 20, 40, 60 and 80°C.
Materials and Methods: RMSD values and frequency of calculated RMSD in the presence and absence of ligands show that ligands cause the relative stability of the G-quadruplex, particularly at low temperatures. The calculation of hydrogen bonds in Guanine-tetrads in three different quadruplex sheets shows that the effect of ligands on the sheets is not the same so that the bottom sheet of G-quadruplex is most affected by the ligands at high temperatures, and the Guaninetetrads in this sheet are far away. Conformation factor was calculated as a measure of ligands binding affinity for each of the G-quadruplex residues.
Results: The results show that the studied ligands interact more with the G-quadruplex than loop areas, although with increasing temperature, the binding area also includes the G-quadruplex sheets. The contribution of each of the residues involved in the G-quadruplex binding area with ligands was also calculated.
Conclusion: The calculations performed are consistent with the previous experimental observations that can help to understand the molecular mechanism of the interaction of phenanthroline and its derivatives with quadruplex.
Phenanthroline, quadruplex, affinity, conformation factor, molecular mechanism, cancer cells.
Faculty of Chemistry, Islamic Azad University, North Tehran Branch, Hakimiyeh, Tehran, Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Faculty of Chemistry, Islamic Azad University, North Tehran Branch, Hakimiyeh, Tehran, Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad