Interaction of anticancer drug doxorubicin with sodium oleate bilayer: Insights from molecular dynamics simulations

The structure of a complex spontaneously formed by the molecule of anticancer drug doxorubicin hydrochloride (DOX) and sodium oleate (OLA) bilayer via non-covalent interactions has been investigated by means of molecular dynamics simulations. It has been shown that non-covalent interactions in the studied system are as strong as to achieve the binding free energy of 55 kJ/mol, which is sufficient to ensure thermodynamic stability of the complex. The spatial structure of the formed complex (orientation of DOX molecule relative to OLA bilayer, atomic composition of the nearest environment of DOX, the conformation of DOX molecule) has been studied in details. The calculated potential of mean force acting between DOX and OLA bilayer has been shown to arise from forces of short-range nature which are most likely to be the solvent-mediated (hydrophilic/hydrophobic) interactions.