In Silico Model Escherichia Coli Membranes: Simulating a Lipid with a Cyclopropane Ring

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Bacterial membranes are composed mostly of lipids with phosphoethanolamine (PE) and phosphoglycerol (PG) head groups and a variety of fatty acid chains. A defining characteristic of bacterial membranes is the presence of lipids with a cyclic-containing chain. To our knowledge, a phospholipid with such a chain has never been studied in a molecular dynamics simulation. Thus, novel force field parameters to describe a cyclopropane moiety were developed using parameters from the CHARMM36 (C36) general force field as a basis and high-level quantum mechanical energies. Two simple membranes and one complex membrane for use as realistic model Escherichia coli (E. coli) cytoplasmic membranes were designed for future work with secondary active transporters expressed in E. coli. Compositions of the membranes were based on several different experimental methods using an E. coli K12 strain grown on Luria broth. One simple membrane consisted of 85 % PE 18:1/16:0 (POPE) and 15 % PG 18:1/16:0(POPG), and the other of only PE cy17:0/16:0 (PMPE). The complex membrane consisted of six different phospholipids, the most prevalent being the cyclic-containing lipid, PMPE. NPT simulations were carried out at 310 K for 50 ns using the C36 lipid force field and the developed cyclopropane moiety force field for each membrane. NMR deuterium order parameters (SCD), density profiles, and diffusion constants are compared with experiment. The model membranes will provide a basis to study membrane bound proteins or other bound molecules expressed in E. coli with realistic molecular dynamic simulations.