Implicit membrane for helical peptide selectivity toward bacterial membranes.

Membrane lipid composition varies significantly across organisms, cell types, and organelles. Mammalian membranes predominantly contain lipids like phosphatidylcholine or sphingomyelin, whereas bacterial membranes are rich in phosphatidylglycerol, phosphatidylethanolamine, and cardiolipin. This diversity in lipid composition presents an opportunity to design peptides that target specific cell types. Particularly, peptides designed to preferentially bind bacterial membranes can have applications to treat bacterial infections while avoiding toxicity. Here, we present a method to identify a broad range of peptide sequences with preferential binding to bacterial membrane models. Using molecular dynamics simulations, we calculated the free energy of insertion for natural amino acid side chains into simplified bacterial and mammalian membranes and implemented a genetic algorithm to identify alpha helical peptide sequences that preferentially adsorb to bacterial membranes. The main limitation of the model is the assumption of helical secondary structure.