Molecular Interactions Between DNA, Cocaine and Its Metabolites

This present work aims to investigate the physical chemical interactions between cocaine and its metabolites with the human-DNA. The investigation was performed by molecular docking and molecular dynamics calculations, where the following cocaine metabolites were analyzed: Benzoylecgonine, Cocaethylene, Ester methylecgonine and Norcocaine. From the docking simulations we observed the hydrogen interactions most likely to occur between the drugs and DNA, whereas, through the molecular dynamics, the RMSD values were obtained and analyzed along with van der Waals, electrostatic, solvation and bind free energies between DNA and cocaine, beside its metabolites. Our results showed that the guanine in the minor groove of DNA is the nucleotide with highest chemical affinity to interact with the cocaine metabolites. On the other hand, the cocaethylene and cocaine were the drugs which presented the most stable and strong interactions with DNA, which can suggest, from molecular modeling investigations, a possible genotoxic potential of these molecules.