Berlin 2018 – wissenschaftliches Programm

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SYMS: Symposium Data-driven Methods in Molecular Simulations of Soft-Matter Systems

SYMS 1: Data-driven Methods in Molecular Simulations of Soft-Matter Systems

SYMS 1.5: Hauptvortrag

Montag, 12. März 2018, 17:15–17:45, H 0105

Computational high-throuhgput screening of drug-membrane thermodynamics — •Tristan Bereau — Max Planck Institute for Polymer Research, Mainz, Germany

The partitioning of small molecules in cell membranes—a key parameter for pharmaceutical applications—typically relies on experimentally-available bulk partitioning coefficients. Computer simulations provide a structural resolution of the insertion thermodynamics via the potential of mean force, but require significant sampling at the atomistic level. Here, we introduce high-throughput coarse-grained molecular dynamics simulations to screen thermodynamic properties. This application of physics-based models in a large-scale study of small molecules establishes linear relationships between partitioning coefficients and key features of the potential of mean force. This allows us to predict the structure of the insertion from bulk experimental measurements for more than 450,000 compounds. The potential of mean force hereby becomes an easily accessible quantity—already recognized for its high predictability of certain properties, such as passive permeation. Further, we demonstrate how coarse graining helps reduce the size of chemical space, enabling a hierarchical approach to screening small molecules.