The Permeation Mechanism of Cisplatin Through a Dioleoylphosphocholine Bilayer**

The investigation of the intermolecular interactions between platinum-based anticancer drugs and lipid bilayers is special relevance to unveil mechanisms involved in different steps mode action these drugs. We have simulated permeation cisplatin through a model membrane composed 1,2-dioleoyl-sn-glycero-3-phosphocholine lipids by means umbrella sampling classical molecular dynamics simulations. initial physisorption into polar region controlled long-range electrostatic with choline groups first step and, second step, hydrogen bond phosphate groups. half pathway, which diffuses nonpolar bilayer, characterized drop heads rise attractive non-polar tails, are dominated van der Waals contributions. free-energy profile explained complex balance drug/lipid energy entropy contributions associated dehydration drug along pathway decrease increase ordering mechanism, respectively.