Abstract
Outer membrane (OM) proteins play a vital role in the physiology of Gram-negative bacteria, and outer membrane protein F (OmpF) is one of the most studied porins in Escherichia coli. In this study, we have developed a comprehensive E. coli OM model with lipopolysaccharides (LPS), enterobacterial common antigen (ECA), and capsular polysaccharides (CPS) in the outer leaflet and with phospholipids in the inner leaflet. Using extensive all-atom molecular dynamics simulations of OmpF in this realistic asymmetric OM environment, we have investigated the structure and dynamics of OmpF within the OM and its interactions with the OM. The results demonstrate that the presence of ECA and CPS enhances the rigidity and stability of the OM while reducing the pore size of OmpF and increasing its cation selectivity. The complex and diverse interactions between OmpF and LPS/ECA/CPS contribute to these effects, resulting in a rigid and compact OmpF structure. These findings provide new insights into the complex interplay between bacterial OM components and OmpF porin, with potential implications for understanding bacterial resistance and developing novel antimicrobial strategies.