(613e) Solute Transport through Outer Membrane Porins of Gram-Negative Bacteria

Porins facilitate the uptake of antibiotic and nutrients across the outer membrane of Gram-negative bacteria like Escherichia coli. In this work, we focus on solute transport through the porin channels by systematically generating the complex outer membrane description of E. coli in molecular-level detail. In general, cell envelope of gram-negative bacteria contains lipopolysaccharide (LPS) rich outer membrane that acts as the first line of defense for bacterial cells in adverse physical and chemical environments. The LPS macromolecule has negatively charged oligosaccharide domain that limits the permeability of charged chemical agents through the membrane. Elucidating the interplay of these contributing macromolecular components and their role in the transport of solutes through porins remains a challenge. To bridge the gap in our current understanding, we have developed a coarse-grained force field to quantify the transport properties through OmpF channels in E. coli outer membrane. The model is computationally affordable for simulating dynamical processes over physiologically relevant timescales. The force field was benchmarked against available experimental and atomistic simulations data for properties such as membrane thickness, density profiles of the residues, the area per lipid, gel to liquid-crystalline phase transition temperatures, and order parameters. A comparison of simulated structural and dynamical properties with corresponding experimental data shows that the developed force field reproduces the overall physiology of solute transport through LPS rich E. coli outer membranes. The simulations provide the molecular mechanisms for permeation of antibiotics through the outer membrane and the strategies that can be employed to develop a new class of antimicrobial agents.