Assessment of the convergence of molecular dynamics simulations of lipopolysaccharide membranes

The outer membrane of Gram-negative bacteria is composed of a phospholipid inner leaflet and a lipopolysaccharide (LPS) outer leaflet. The chemical structure of LPS results in an asymmetric character of outer membranes that has been shown to play an important role in the electrical properties of porins, low permeability and intrinsic antibiotic resistance of Gram-negative bacteria. Atomistic molecular dynamics simulations of two different configurations of the outer membrane of Pseudomonas aeruginosa under periodic boundary conditions were carried out in order to (1) validate model-derived properties against the available experimental data, (2) identify the properties whose dynamics can be sampled on nanosecond timescales, and (3) evaluate the dependence of the convergence of structural and dynamical properties on the initial configuration of the system, within the chosen force field and simulation conditions. Because the relaxation times associated with the motions of individual LPS monomers in outer membranes are very long, the two initial configurations do not converge to a common ensemble of configuration on the nanosecond time scale. However, a number of properties of the outer membrane that will significantly impact the structural and internal dynamics of transmembrane proteins, most notably the electrostatic potential and molecular density, do converge within the simulated time scale. For these properties, a good agreement with the available experimental data was found. Such a molecular model, capable of accounting for the high asymmetry and low fluidity characteristics of outer membranes provides a more appropriate environment for atomistic simulations of outer membrane proteins.