Modeling the electrostatic potential of asymmetric lipopolysaccharide membranes: The MEMPOT algorithm implemented in DelPhi

• Published in: Journal of computational chemistry 2014-07, Vol.35 (19), p.1418-1429
• Main Authors: Dias, Roberta P., Li, Lin, Soares, Thereza A., Alexov, Emil
• Format: Article
• Language: English
• Subjects: Algorithms; Biochemistry; Calcium ions; Dielectric properties; Electrostatics; Frame structures; glycolipids; Gram-negative bacteria; Hydrophobic surfaces; Investigations; Lipids; Lipopolysaccharides - chemistry; lipopolysaccharides phenotype variation; Membranes; Modelling; Models, Chemical; Molecular dynamics; multiple dielectric constants; outer membrane remodeling; Permittivity; phospholipid bilayers; Poisson Distribution; Poisson-Boltzmann equation; Simulation; Static Electricity; transmembrane potential
• ISSN: 0192-8651; 1096-987X
• DOI: 10.1002/jcc.23632

Four chemotypes of the rough lipopolysaccharides (LPS) membrane from Pseudomonas aeruginosa were investigated by a combined approach of explicit water molecular dynamics (MD) simulations and Poisson–Boltzmann continuum electrostatics with the goal to deliver the distribution of the electrostatic potential across the membrane. For the purpose of this investigation, a new tool for modeling the electrostatic potential profile along the axis normal to the membrane, MEMbrane POTential (MEMPOT), was developed and implemented in DelPhi. Applying MEMPOT on the snapshots obtained by MD simulations, two observations were made: (a) the average electrostatic potential has a complex profile but is mostly positive inside the membrane due to the presence of Ca2+ ions, which overcompensate for the negative potential created by lipid phosphate groups; and (b) correct modeling of the electrostatic potential profile across the membrane requires taking into account the water phase, while neglecting it (vacuum calculations) results in dramatic changes including a reversal of the sign of the potential inside the membrane. Furthermore, using DelPhi to assign different dielectric constants for different regions of the LPS membranes, it was investigated whether a single frame structure before MD simulations with appropriate dielectric constants for the lipid tails, inner, and the external leaflet regions, can deliver the same average electrostatic potential distribution as obtained from the MD‐generated ensemble of structures. Indeed, this can be attained by using smaller dielectric constant for the tail and inner leaflet regions (mostly hydrophobic) than for the external leaflet region (hydrophilic) and the optimal dielectric constant values are chemotype‐specific. © 2014 Wiley Periodicals, Inc. The rough lipopolysaccharides (LPS) membrane is an important component of the bacterial outer membrane. To investigate the distribution of the electrostatic potential across LPS membranes, molecular dynamics simulations and Poisson–Boltzmann calculations with an implicit water model are performed on four different chemotypes of the rough LPS. A tool termed MEMPOT (MEMbrane POTential) is developed in the DelPhi program to calculate the average membrane crossing electrostatic potential.