Characterization of cisplatin/membrane interactions by QM/MM energy decomposition analysis.

We extend for the first time a quantum mechanical energy decomposition analysis scheme based on deformation electron densities to a hybrid electrostatic embedding quantum mechanics/molecular mechanics framework. The implemented approach is applied to characterize the interactions between cisplatin and a dioleyl-phosphatidylcholine membrane, which play a key role in the permeation mechanism of the drug inside the cells. The interaction energy decomposition into electrostatic, induction, dispersion and Pauli repulsion contributions is performed for ensembles of geometries to account for conformational sampling. It is evidenced that the electrostatic and repulsive components are predominant in both polar and non-polar regions of the bilayer.