Bacterial Outer Membranes and Interactions with Membrane Proteins

Abstract

Because the bacteria's outer membrane (OM) acts as an effective barrier against the permeation of both hydrophobic and hydrophilic compounds, gram-negative cell permeation is one of the biggest challenges to the discovery of novel antibiotics for bacterial infections and antibiotic resistance worldwide. The bacterial OM is a unique and highly asymmetric lipid bilayer composed of phospholipids in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet. An LPS molecule is a complex amphiphatic compound consisting of lipid A, a core oligosaccharide, and an O-antigen polysaccharide. Despite the direct relationship of gram-negative bacteria to the public health and also the fact that there are over 190 identified O-serotypes for Escherichia coli, our molecular-level understanding of how the bacterial OMs behave and work for various types of bacteria, how membrane proteins behave in the OM, and how known drug molecules and potential drugs can enter through the OMs is rudimentary at best. This talk presents our ongoing efforts on all-atom modeling and simulations of these complex bacterial OMs with and without various outer membrane proteins using the CHARMM36 (protein, lipid, carbohydrate) force fields. In addition, various technical aspects and perspectives are also discussed together with future developments of CHARMM-GUI LPS Modeler and OM Builder.