Refinement of OprH-LPS Interactions by Molecular Simulations

The outer membrane (OM) of Gram-negative bacteria is composed of lipopolysaccharide (LPS) in the outer leaflet and phospholipids in the inner leaflet. The outer membrane protein H (OprH) of Pseudomonas aeruginosa provides an increased stability to the OMs by directly interacting with LPS. Here we report the influence of various P. aeruginosa and, for comparison, Escherichia coli LPS environments on the physical properties of the OMs and OprH using all-atom molecular dynamics simulations. The simulations reveal that although the P. aeruginosa OMs are thinner hydrophobic bilayers than the E. coli OMs, which is expected from the difference in the acyl chain length of their lipid A, this effect is almost imperceptible around OprH due to a dynamically adjusted hydrophobic match between OprH and the OM. The structure and dynamics of the extracellular loops of OprH show distinct behaviors in different LPS environments. Including the O-antigen greatly reduces the flexibility of the OprH loops and increases the interactions between these loops and LPS. Furthermore, our study shows that the interactions between OprH and LPS mainly depend on the secondary structure of OprH and the chemical structure of LPS, resulting in distinctive patterns in different LPS environments.