Molecular Dynamics Simulation Studies of Interactions of E. coli-K12 with OmpF in Outer Membranes: Effects of LPS Structures on Monoclonal Antibodies Binding

Gram-negative bacterial outer membrane, which is a highly asymmetric lipid bilayer, is composed of an outer membrane protein along with phospholipids (PLs) forming the inner leaflet and lipopolysaccharides (LPSs) forming the outer leaflet. Outer membrane protein F (OmpF) porin is a trimeric integral membrane protein responsible for the passive transport of small hydrophilic molecules such as nutrients and waste products across the outer membrane of Escherichia coli (E. coli). Here, we report the structural properties of a model of the E. coli-K12 outer membrane and its interaction with OmpF using molecular dynamics simulations. Immunochemical and other experiments suggested several cell-surface exposed epitopes (antibody binding sites), which were recognized by various monoclonal antibodies (MAbs). Molecular details of interaction between LPS core sugars and surface of OmpF suggest the importance of LPS core sugars in shielding of these epitopes. Results are compared with experimental evidence, which showed that with shortening of the LPS core sugars (rfa E. coli-K-12 mutants), the number of MAbs, that recognized porin surface epitopes, increased sequentially. To check the stabilizing effect of LPS structure on the extracellular loop conformations, results of interaction between OmpF and asymmetric E. coli-K12 bilayer are compared to those from OmpF simulations in a DMPC bilayer. In addition, overall membrane properties such as, electron density profiles, per-lipid surface area of each lipid type, and chain order parameters are compared with E.coli-K12 outer membrane in absence of OmpF. These results are also compared to our previous molecular dynamics results with E. coli-R1 outer membrane with OmpLA. Overall, membrane structural properties are comparable, however, individual lipid properties showed slight variations.