Lipid Bilayers Driven to a Wrong Lane in Molecular Dynamics Simulations by Subtle Changes in Long-Range Electrostatic Interactions

Abstract

We provide compelling evidence that different treatments of electrostatic interactions in molecular dynamics simulations may dramatically affect dynamic properties of lipid bilayers. To this end, we consider a fully hydrated pure dipalmitoylphosphatidylcholine bilayer through 50-ns molecular dynamics simulations and study various dynamic properties of individual lipids in a membrane, including the velocity autocorrelation function, the lateral and rotational diffusion coefficients, and the autocorrelation function for the area per molecule. We compare the results based on the Particle-Mesh Ewald (PME) and reaction field (RF) techniques with those obtained by an approach where the electrostatic interactions are truncated at r cut = 1.8, 2.0, and 2.5 nm. We find that the overall performance of PME is very good; its results are consistent with the expected behavior. The RF method performs rather well, too, despite certain inherent problems and the fact that its results differ from those obtained by PME. Nevertheless, the largest differences are found for the truncation methods, for which all examined truncation methods lead to results distinctly different from those obtained by PME. The lateral diffusion coefficients obtained by PME and truncation at 1.8 nm, for example, differ by a factor of 10, while the PME results are consistent with experimental values. The observed deviations can be interpreted in terms of artificial ordering due to truncation and highlight the important role of electrostatic interactions in the dynamics of systems composed of lipids and other biologically relevant molecules such as proteins and DNA.

Effect of NaCl and KCl on Phosphatidylcholine and Phosphatidylethanolamine Lipid Membranes: Insight from Atomic-Scale Simulations for Understanding Salt-Induced Effects in the Plasma Membrane

“…For the electrostatic interactions, we used the particle-mesh Ewald method 32,33 which has been shown to perform very well in membrane simulations. [34][35][36] Simulations were performed in the NpT ensemble at the physiological temperature (T ) 310 K) and at a pressure set to 1 bar; temperature and pressure were kept constant by the Berendsen scheme. 37 The time step used in all simulations was 2 fs.…”

Ionic Surfactant Aggregates in Saline Solutions: Sodium Dodecyl Sulfate (SDS) in the Presence of Excess Sodium Chloride (NaCl) or Calcium Chloride (CaCl2)

“…57 Time step of 2 fs was used in all of the simulations reported here. The Lennard-Jones interactions were cut off at 1 nm, and the full particle-mesh Ewald method 58 was employed for the long-ranged electrostatic interactions; not fully accounting for these long-ranged electrostatic interactions has been shown to lead to serious artifacts in the simulations of amphiphilic molecules, 59,60 and contrary to the rather common misconception, proper treatment of electrostatics is also computationally efficient. 61 The SDS parameters are not part of the standard Gromacs force field.…”

Coarse-grained model for phospholipid/cholesterol bilayer

“…51,52,53 The parameters for bonded and non-bonded interactions for DPPC molecules were taken from a study of a pure DPPC bilayer, 54 and partial charges from the underlying model description. 53 The cholesterol force field was taken from an earlier study.…”