Modeling and simulation of bacterial outer membranes and interactions with membrane proteins

The outer membrane (OM) of Gram-negative bacteria is composed of phospholipids in the periplasmic leaflet and lipopolysaccharides (LPS) in the external leaflet, along with beta-barrel OM proteins (OMPs) and lipidated periplasmic lipoproteins. As a defensive barrier to toxic compounds, an LPS molecule has high antigenic diversity and unique combination of OM-anchored lipid A with core oligosaccharides and O-antigen polysaccharides, creating dynamic protein-LPS and LPS-LPS interactions. Here, we review recent efforts on modeling and simulation of native-like bacterial OMs to explore structures, dynamics, and interactions of different OM components and their roles in transportation of ions, substrates, and antibiotics across the OM and accessibility of monoclonal antibodies (mAbs) to surface epitopes. Simulation studies attempting to provide insight into the structural basis for LPS transport and OMP insertion in the bacterial OM are also highlighted.