Molecular dynamics simulation of a phospholipid membrane

Abstract

We present the results of molecular dynamics (MD) simulations of a phospholipid membrane in water, including full atomic detail. The goal of the simulations was twofold: first we wanted to set up a simulation system which is able to reproduce experimental results and can serve as a model membrane in future simulations. This goal being reached it is then further possible to gain insight in to those properties that are experimentally more difficult to access. The system studied is dipalmitoylphosphatidylcholine/water, consisting of 5408 atoms. Using original force field parameters the membrane turned out to approach a gel-like state. With slight changes of the parameters, the system adopted a liquid-crystalline state. Separate 80 ps runs were performed on both the gel and liquid-crystalline systems. Comparison of MD results with reliable experimental data (bilayer repeat distance, surface area per lipid, tail order parameters, atom distributions) showed that our simulations, especially the one in the liquid-crystalline phase, can serve as a realistic model for a phospholipid membrane. Further analysis of the trajectories revealed valuable information on various properties. In the liquid-crystalline phase, the interface turns out to be quite diffuse, with water molecules penetrating into the bilayer to the position of the carbonyl groups. The 10-90% width of the interface turns out to be 1.3 nm and the width of the hydrocarbon interior 3.0 nm. The headgroup dipoles are oriented at a small angle with respect to the bilayer plane. The resulting charge distribution is almost completely cancelled by the water molecules. The electron density distribution shows a large dip in the middle of the membrane. In this part the tails are more flexible. The mean life time between dihedral transitions is 20 ps. The average number of gauche angles per tail is 3.5. The occurrence of kinks is not a significant feature.

Validation of the GROMOS force-field parameter set 45A3 against nuclear magnetic resonance data of hen egg lysozyme

“…The validation of improved force-field parameter sets through MD simulations of proteins is an essential step towards the understanding of biomolecular behaviour. The older GROMOS parameter set 43A1 did perform well for proteins, but not for lipids, which were generally simulated using a special set of parameters tailored for membranes (Egberts et al, 1994). The new parameter set 45A3 was calibrated including long (up till 18 carbon atoms) aliphatic chains (Schuler et al, 2001) and should, therefore, be suitable not only for proteins, but for lipid aggregates too.…”

Structure and dynamics of water and lipid molecules in charged anionic DMPG lipid bilayer membranes

“…Because the hybrid force field uses pseudo-atoms along the chains, we need to "reconstruct" the methylene hydrogen atom positions. Following the procedure given by Egberts et al, 32 for determining the H-positions, we calculate an NMR order parameter, which is analogous to that for an all-atom model. The results in Fig.…”

Thermodynamic study of benzocaine insertion into different lipid bilayers

“…A scheme of the benzocaine molecule used in this work is shown in Figure 1. The force field parameters and electrostatic charge distribution of the DPPC and DPPS were the same as those used by Egberts et al 27 and Cascales et al 28 in previous simulations of pure bilayers of DPPC and DPPS in their liquid crystalline state. The charge distribution and force field parameters for benzocaine were taken from a previous article.…”