Insight into toxicity via free energy profiles of chemicals passing though a membrane
Octanol/water (log POW) and membrane/water (log PMW) partition coefficients of a substance measure its solubility in octanol/membrane compared to water. They can be seen as simple models for the compound's solubility in biological membranes, which ultimately is a rough estimate for toxicity. This can e.g. be an important issue for the development of new additives for common industrial products like lubricants. On the other hand, for novel drugs it might be crucial to enter the cell through the membrane, or even integrate into it.
Molecular dynamic simulations allow to calculate reliable log POW values from atomistic simulations, even for substances with concentration-dependent log POW like ionic liquids. Our method is based on the calculation of solvation free energies in water and octanol using thermodynamic integration.
In the same manner we predict Log PMW values of chemicals via umbrella sampling. We obtain free enthalpy profiles along the compound's path though the membrane and can search for relations between the energetic barrier and the observed toxicity.