In-silico Analysis of Chemical Space Governing the Interactions between Distamycin A Derivatives and DNA Molecule

Targeting DNA lies at the heart of anti-cancer therapies. Hence, DNA-binding drugs and their interaction with DNA have recently drawn the attention of researchers. Since DNA minor groove binders (MGBs) act as potent anti-tumor agents, there is a need to have detailed insights on how they interact with DNA. The mechanism of action of the majority of MGBs is not well studied at the molecular level. Herein, molecular docking and dynamics simulations were performed, using AutoDock Vina and NAMD softwares, respectively, to evaluate the binding of A derivatives (Tallimustine, PNU 151807, and ) to , and to compare their interaction energy and binding patterns. All three drugs were stably bound throughout the simulation, causing only minor modifications to the structure of DNA. Results of interaction energy analyses together with LigPlot outcomes showed that A/T residues are responsible for making the majority of non-bonding interactions in the case of all three drugs, showing a good agreement with previously reported findings on MGBs. A/T residues are responsible for making the majority of non-bonding interactions in the case of all three drugs, showing a good agreement with previously reported findings on MGBs. Furthermore, our studies have shown that to the other members of the Distamycin A family, makes stronger interactions with , making it a better candidate for cancer therapy goals.