Regensburg 2019 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 12: Poster II

BP 12.25: Poster

Dienstag, 2. April 2019, 14:00–16:00, Poster B2

Computational optimization of compound selectivity to different membrane environments — Bernadette Mohr and •Tristan Bereau — Max Planck Institute for Polymer Research

Current virtual screening approaches reduce the computational cost by using simplified representations and approximations, statistical mechanical effects are excluded. We investigate one way to include the effects determining the selectivity of a molecule to a specific target into virtual screening by using physics-based models. Coarse-grained simulations are introduced as a preliminary step to allow the effective screening of a large number of molecules. As a test case, the physical and chemical properties of the fluorescent dye 10-N-nonyl acridine orange are modified to increase its binding affinity to Cardiolipin. In eukaryotes, Cardiolipin is almost exclusively found in the inner mitochondrial membrane. Mitochondria are the location of important metabolic pathways and are linked to diseases and apoptosis. Therefore, targeting a lipid specific to mitochondria is of great interest. In the coarse-grained representation, the bead types at selected positions of the acridine orange molecule are changed and the difference in binding affinity between the original and modified structures are determined by free energy calculations. The present results from the coarse-grained simulations indicate that hydrogen bonding has the desired effect. As a next step, the information lost in the coarse-graining process is to be reintroduced to a small subset of the screened molecules by repeating the free energy calculations in atomistic detail.