Linking the Outer Membrane of E.Coli to the Cell Wall via OMPA & Braun's Lipoprotein: Towards a Molecular Model of a Virtual Bacterial Cell Envelope

Abstract

In the last couple of years molecular dynamics simulations of bacterial membranes have reached unprecedented levels of detail. In particular the outer membrane of Gram-negative bacteria is now being routinely simulated as an asymmetric membrane, incorporating lipopolysaccharide (LPS) molecules in the outer leaflet and a realistic mixture of phospholipids in the inner leaflet, at the atomistic level of detail. However to move towards a more systems approach to simulating the whole cell envelope, the cell wall must be considered. Here we present our progress on simulating the full-length OmpA protein in its monomeric and dimeric forms anchored in the outer membrane but also bound to peptidoglycan of the cell wall. Our results reveal considerable flexibility in the OmpA linker, predict stable binding of the peptidoglycan to the C-terminal domain and reveal hitherto unexplored details of the dimerization interface in a realistic membrane environmentFurthermore, we also discuss our models of Braun's lipoprotein, which also provides a link between these two components of the cell envelope. In summary we present our progress towards detailed models of an entire bacterial organelle.