Modeling and Simulation of Outer Membranes with LPS, ECAs, and CPs

Abstract

In addition to lipopolysaccharides (LPS), glycolipids such as enterobacterial common antigens (ECAs) and capsular polysaccharides (CPS) also play a critical role in the biological functions of various Gram-negative bacterial outer membranes (OMs). Characterizing their structure and dynamics at the molecular level will provide an in-depth understanding of various OMs with different LPS, ECAs, and CPS. However, systematic generation of all-atom OM structural models including various LPS, ECAs, and/or CPS is challenging because of complex variations in the lipid structures and glycan sequences (i.e., carbohydrate types and their linkages). To facilitate the generation of all-atom ECAs/CPS structures, in addition to existing LPS Modeler in CHARMM-GUI (http://www.charmm-gui.org), we have developed ECA Modeler and CPS Modeler, a web-based interface that simplifies building of complex biological simulation systems. In addition, we will incorporate the two modules into Membrane Builder, so that researchers can readily build various LPS/ECAs/CPS-containing membrane systems. These tools are expected to provide further insight into structures, dynamics, and underlying mechanisms of complex bacterial outer membranes, and also help to investigate how outer membrane proteins (OMPs) interact with and behave in various LPS/ECAs/CPS-containing OMs.