The Effect of Lipopolysaccharides on the Electrostatic Properties of Gram-Negative General Porins from Enterobacteriaceae

We investigated, by using all-atom molecular dynamics simulations, the effect of the outer membrane of Gram-negative bacteria, composed in the outer leaflet by polar/charged lipopolysaccharides (LPS), on the electrostatic properties of general porins from the Enterobacteriaceae family. General porins constitute the main path for the facilitated diffusion of polar antibiotics through the outer membrane. As model system we selected OmpK36 from Klebsiella pneumoniae, the ortholog of OmpC from Escherichia coli. This species presents high variability of amino acid composition of porins, with the effect to increase its resistance to the penetration of antibiotics. The various properties we analyzed seem to indicate that LPS acts as an independent layer without affecting the internal electrostatic properties of OmpK36. The only apparent effect on the microsecond time scale we sampled is the appearance of calcium ions, when present at moderate concentration in solution, inside the pore. However, we noticed increased fluctuations of the polarization density and only minor changes on its average value.We analyzed structural and electrostatic properties of the porin OmpK36 within various membrane environments, including the lipopolysaccharide from Klebsiella pneumoniae and Escherichia coli, and a POPC bilayer. Our results reveal distinct influences of the different environments: while the average value of the transversal electric field remains relatively constant, the environments modulate its fluctuations, suggesting a subtle role of the surrounding. image