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BP: Fachverband Biologische Physik

BP 36: Molecular Dynamics (Focus Session)

BP 36.5: Talk

Wednesday, March 9, 2016, 10:45–11:00, H43

High-throughput thermodynamics of drug-membrane interactions from multiscale simulations — •Tristan Bereau and Kurt Kremer — Max Planck Institute for Polymer Research, Mainz

The number of small organic molecules is overwhelmingly large--so large, that most of it remains unexplored. Computer simulations offer an appealing framework to probe many of these compounds without the need to synthesize them in the laboratory. The main hurdles preventing a high-throughput characterization of many small molecules relies on the time investment to parametrize the force field---a process that typically requires significant human intervention---and extensive sampling requirements. We address these issues by first sampling from the coarse-grained Martini model, for which we developed an automated parametrization protocol for small molecules. The resulting potential-of-mean-force (PMF) curves for the insertion of small molecules in lipid membranes show excellent agreement for a number of benchmark cases. We further use the coarse-grained trajectory as an enhanced-sampling strategy to efficiently estimate the corresponding atomistic PMF. To illustrate the method, we rationalize experimental observations of lipid-domain formation in bacterial membranes after the insertion of a small alcohol compound. This framework enables a fast and efficient strategy to gain insight in the thermodynamic properties of drug-membrane interactions.