(303h) Coarse Grained Parameterization of Gram-Negative Bacterial Outer Membrane

To study the molecular complexity and dynamics of the gram-negative bacterial membrane, we have developed coarse grained parameter set for the lipopolysaccharide rich bilayer assembly of the outer membrane. The membrane acts as the first line of defense for bacterial cells in adverse physical and chemical environments.  Besides the lipopolysaccharide, the outer membrane has radially extending O-antigen polysaccharide chains and β-barrel membrane proteins that make the bacterial membrane physiologically unique compared to phospholipid cell membranes. The coarse grained model compatible with the MARTINI force field was benchmarked against available experimental and atomistic simulations data for properties such as membrane thickness, density profiles of the residues, area per lipid, gel to liquid-crystalline phase transition temperatures, order parameters, and radial distribution functions. More than 17 membrane compositions were studied with a combined simulation time of over 100 microseconds. A comparison of simulated structural and dynamical properties with corresponding experimental data shows that the developed parameter set reproduces the overall physiology of lipopolysaccharide membranes. The coarse grained model of the outer membrane makes long timescale simulations feasible, which can be instrumental in designing effective antibiotics with enhanced outer membrane permeation properties.