A Comparative Study of Perylene Di‐Imide and Triethylene Tetramine With c‐KIT Quadruplex DNA: Molecular Dynamics Simulation

ABSTRACT G‐quadruplex DNA, also known as quadruplex DNA, is a unique secondary structure formed by guanine‐rich sequences that fold into four‐stranded configurations. These structures are located in biologically important regions such as telomeres and gene promoter areas. In this study, we selected two ligands Triethylene Tetramine (TETA) and perylene di‐imide (PDI), which are small molecules capable of binding to and stabilizing G‐quadruplex structures. This property is particularly significant in the context of anticancer drug development. We used docking and 1200 ns molecular dynamics simulations in the AMBER 14 environment to conduct a comparative analysis. Systems were modeled with the AMBER nucleic acid force field, solvated using the TIP3P water model, and neutralized with Na + ions under periodic boundary conditions. We conducted a comparative analysis of the interactions between these ligands and the c‐KIT G‐quadruplex DNA. Our results (docking score, RMSD, RMSF, hydrogen bonding, MMPBSA/MMGBSA binding energy) demonstrate that TETA exhibits superior binding properties compared to PDI in stabilizing the c‐KIT G4 DNA. Thus, TETA may serve as a more promising candidate than PDI for potential anticancer therapeutic applications.