Combination of COSMOmic and molecular dynamics simulations for the calculation of membrane-water partition coefficients.

The importance of membrane-water partition coefficients led to the recent extension of the conductor-like screening model for realistic solvation (COSMO-RS) to micelles and biomembranes termed COSMOmic. Compared to COSMO-RS, this new approach needs structural information to account for the anisotropy of colloidal systems. This information can be obtained from molecular dynamics (MD) simulations. In this work, we show that this combination of molecular methods can efficiently be used to predict partition coefficients with good agreement to experimental data and enables screening studies. However, there is a discrepancy between the amount of data generated by MD simulations and the structural information needed for COSMOmic. Therefore, a new scheme is presented to extract data from MD trajectories for COSMOmic calculations. In particular, we show how to calculate the system structure from MD, the influence of lipid conformers, the relation to the COSMOmic layer size, and the water/lipid ratio impact. For a 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer, 66 partition coefficients for various solutes were calculated. Further, 52 partition coefficients for a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer system were calculated. All these calculations were compared to experimental data.