Molecular Dynamics Simulations of Mixed Acidic/Zwitterionic Phospholipid Bilayers

Abstract

Anionic lipids are key components in the cell membranes. Many cell-regulatory and signaling mechanisms depend upon a complicated interplay between them and membrane-bound proteins. Phospholipid bilayers are commonly used as model systems in experimental or theoretical studies to gain insight into the structure and dynamics of biological membranes. We report here 200-ns-long MD simulations of pure (DMPC and DMPG) and mixed equimolar (DMPC/DMPG, DMPC/DMPS, and DMPC/DMPA) bilayers that each contain 256 lipids. The intra- and intermolecular interaction patterns in pure and mixed bilayers are analyzed and compared. The effect of monovalent ions (Na+) on the formation of salt-bridges is investigated. In particular, the number of Na(+)-mediated clusters in the presence of DMPS is higher than with DMPG and DMPA. We observe a preferential clustering of DMPS (and to some extent DMPA) lipids together rather than with DMPC molecules, which can explain the phase separation observed experimentally for DMPC/DMPS and DMPC/DMPA bilayers.

Thermodynamics of the binding of Substance P to lipid membranes

“…According to the molecular dynamics simulation research of Broemstrup et al, DMPS molecules are known to bond more strongly with Na + than DMPG molecules do. 21 It means that the anion in the carboxyl group of the DMPS molecule strongly bonds with the Na + cation.…”

Integrating cluster formation and cluster evaluation in interactive visual analysis

“…Molecular dynamics (MD) simulations are utilized as powerful tools to describe the atomic structure and dynamics of lipid bilayers, since detailed structural data of the most biologically relevant phases is difficult to obtain experimentally. In particular mixtures containing more than one lipid type have been studied in order to understand how different lipid types cluster together and can lead to inhomogeneity in biological membranes [Broemstrup and Reuter 2010]. Unfortunately, data generated by MD simulations can be rather tedious to analyze.…”

“…The MD dataset of a mixed lipid bilayer [Broemstrup and Reuter 2010] is constituted of DMPC (dimirystoilphosphatidylcholine) and DMPG (dimirystoilphosphatidylglycerol) lipids. Each lipid is represented by one particle, localized at the position of the phosphorus atom.…”

“…In one clustering procedure of lipid bilayers, we employed only the last 100 time steps from all 1640 frames to perform clustering analysis, due to the system stabilization [Broemstrup and Reuter 2010]. The clustering analysis pointed out a new issue that is to evaluate the influence of 'jumpers' on the clustering process.…”

“…Nevertheless, usually all the simulated particles are employed for the cluster analysis. On one hand, the exploited clustering technique [Broemstrup and Reuter 2010] that is used to analyze the MD simulation, takes every time step separately. Therefore such particles do not have to be considered as outliers.…”