The investigation of the association of caffeine and actinocin derivatives in aqueous solution: A molecular dynamics simulation

The association of caffeine (Cf) and the analogue of the anticancer antibiotic Actinomycin D-actinocin derivative ActII was studied by molecular dynamics simulation. The simulation was carried out with explicit water molecules and Na+ and Cl− ions. The hydration scheme of monomer and associated forms of caffeine and ActII were determined. The calculated values of interaction energies of monomers in dimers show that the aggregation of these compounds in aqueous solutions is the energetically favorable process. The self- and hetero-associates were stabilized by van-der-Waals, electrostatic and hydrophobic interactions and also due to formation of intermolecular hydrogen bonds. The reconstruction of hydration shells of monomers after their association in solution was energetically unfavorable and destabilized the dimer formation. The formation of heterodimers Cf-ActII was energetically more favorable than formation of the self-associates of caffeine. Therefore caffeine can decrease concentration of actinocin derivative in solution by the formation of hetero-associates and hence leads to the decrease of the pharmacological activity of the analogue of anticancer antibiotic acting as interceptor.