Dresden 2011 – scientific programme
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BP: Fachverband Biologische Physik
BP 16: Biological Membranes I
BP 16.8: Talk
Tuesday, March 15, 2011, 12:30–12:45, ZEU 260
Calculating Partition Coefficients From Atomistic Computer Simulations — •Axel Arnold1, Thorsten Köddermann2, and Dirk Reith2 — 1ICP, Universität Stuttgart, Germany — 2Fraunhofer SCAI, St. Augustin, Germany
The partition coefficient (log POW) of a substance measures its solubility in octanol compared to water. This can be seen as a simple model for its solubility in biological membranes, which is a rough estimate for toxicity. If a substance is hardly soluble in octanol, it is practically impossible for it to enter (human) cells, and therefore it is less likely to be toxic. On the other hand, for novel drugs it might be important to penetrate the cell through the membrane, or even integrate into it.
Being able to determine the log POW a priori from computer simulations would therefore be an important step towards virtual drug design. Up to now, heuristic approaches based on functional groups are mostly used to estimate the log POW, and only there were only a few computer simulations studies trying to calculate the partition coefficient ab initio.
We present a method to reliably calculate log POW values from atomistic computer simulations. It is based on the calculation of solvation free energies using thermodynamic integration. First results demonstrate that this generic approach is able to predict log POW values for alcohols better than the classical heuristic methods.