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.