Computer simulation of the association of caffeine and actinocin derivatives in aqueous solutions

The association of caffeine and actinocin derivatives (ActII), the analogues of anticancer antibiotic actinomycin D, was studied by molecular dynamics simulation. The simulation was carried out with consideration of solvent molecules, water and Na+ and Cl- ions. The information was obtained which describes in detail the association of caffeine and ActII in water and aqueous-salt solutions and interaction of monomers and dimers with water-ion environment. The hydration schemes for monomers 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 an energetically favorable process. The self- and heteroassociates were stabilized by van-der-Waals, electrostatic, and hydrophobic interactions and also due to the formation of intermolecular hydrogen bonds. The reconstruction of hydration shells of monomers after their association in water is energetically unfavorable and destabilizes the dimer formation. The reconfiguration of hydration shell of monomers after their association in the presence of Na+ and Cl- ions is energetically favorable for dimer of singly charged ActII(+) and heteroassociates Cf-ActII(+). The formation of heterodimers Cf-ActII is energetically more favorable than the formation of self-associates of caffeine. Therefore, caffeine can decrease the concentration of aromatic biologically active compounds, actinocin derivatives, in solution through the formation of heteroassociates and hence lead to a decrease in the pharmacological activity of the analogues of anticancer antibiotic acting as an interceptor.