Simulations of biomembranes and water: Important technical aspects (original) (raw)
Related papers
Biophysical Journal, 1995
In this paper we report on the molecular dynamics simulation of a fluid phase hydrated dimyristoylphosphatidylcholine bilayer. The initial configuration of the lipid was the x-ray crystal structure. A distinctive feature of this simulation is that, upon heating the system, the fluid phase emerged from parameters, initial conditions, and boundary conditions determined independently of the collective properties of the fluid phase. The initial conditions did not include chain disorder characteristic of the fluid phase. The partial charges on the lipids were determined by ab initio self-consistent field calculations and required no adjustment to produce a fluid phase. The boundary conditions were constant pressure and temperature. Thus the membrane was not explicitly required to assume an area/phospholipid molecule thought to be characteristic of the fluid phase, as is the case in constant volume simulations. Normal to the membrane plane, the pressure was 1 atmosphere, corresponding to the normal laboratory situation. Parallel to the membrane plane a negative pressure of -100 atmospheres was applied, derived from the measured surface tension of a monolayer at an air-water interface. The measured features of the computed membrane are generally in close agreement with experiment. Our results confirm the concept that, for appropriately matched temperature and surface pressure, a monolayer is a close approximation to one-half of a bilayer. Our results suggest that the surface area per phospholipid molecule for fluid phosphatidylcholine bilayer membranes is smaller than has generally been assumed in computational studies at constant volume. Our results confirm that the basis of the measured dipole potential is primarily water orientations and also suggest the presence of potential barriers for the movement of positive charges across the water-headgroup interfacial region of the phospholipid.
Interactions of Lipid Bilayers with Supports: A Coarse-Grained Molecular Simulation Study
The Journal of Physical Chemistry B, 2008
The study of lipid structure and phase behavior at the nanoscale is of utmost importance due to implications in understanding the role of the lipids in biochemical membrane processes. Supported lipid bilayers play a key role in understanding real biological systems, but they are vastly underrepresented in computational studies. In this paper, we discuss molecular dynamics simulations of supported lipid bilayers using a coarse-grained model. We first focus on the technical implications of modeling solid supports for biomembrane simulations. We then describe noticeable influences of the support on the systems. We are able to demonstrate that the bilayer system behavior changes when supported by a hydrophilic surface. We find that the thickness of the water layer between the support and the bilayer (the inner-water region in the latter part of this paper) adapts through water permeation on the microsecond time scale. Additionally, we discuss how different surface topologies affect the bilayer. Finally, we point out the differences between the two leaflets induced by the
Compatibility of advanced water models with a united atom model of lipid in lipid bilayer simulation
The Journal of Chemical Physics, 2019
Molecular dynamics simulation of lipid bilayers generally uses all-atom, united-atom, and coarse-grained models of lipid molecules. The GROMOS united-atom model of lipid constructs a balance between accuracy and computational cost. The above-mentioned model satisfactorily reproduces many of the structural and dynamical properties of different lipid bilayers. However, the GROMOS force field is parameterized only with the SPC model of water. Unfortunately, SPC is not an excellent model of water for predicting the structure and dynamics of the interfacial water near the lipid bilayer. More advanced water models, such as TIP3P-FB and TIP4P-FB, outperform the SPC model in predicting different thermodynamic and microscopic properties of bulk water. This motivates us to check the compatibility of five different water models, including SPC, with the GROMOS96 53A6L united atom model of two different lipid bilayers, DPPC and POPC. A systematic comparison of the bilayer structure and dynamics,...
Aqueous Solutions next to Phospholipid Membrane Surfaces: Insights from Simulations
Chemical Reviews, 2006
The structure of water next to the biomembrane surface and its role in the interaction between biomembranes were actually among the first issues investigated in the initial simulations performed on model biomembranes in the early nineties. 25-29 Experimental studies that used osmotic stress techniques demonstrated that the force of interaction acting between model membrane surfaces containing molecules such as dipalmitoylphosphatidylcholine (DPPC) is repulsive and that the decay of this force has an exponential character 9 with the decay exponent λ having a value in the range 0.1s 0.3 nm. The fact that the value of λ is close to the size of a water molecule, naturally, triggered the idea that interbilayer water is responsible for this force, and therefore, it was called the "hydration force". Accordingly, it was assumed that the origin of the force was due to the removal of structured water between lipid bilayers, which requires work to be done and therefore results in an increase of free energy as the distance between bilayers decreases. At the same time, another explanation for the origin of the hydration force was proposed: the force is due to steric interactions between the headgroups of lipid molecules that protrude from the surfaces. 30 A series of theoretical papers investigated the nature of the hydration force, providing arguments in favor of one or the other point of view. 30-41 McIntosh and Simon performed a series of experiments using substitutions in the structure of lipid molecules to study the nature of the hydration force acting between bilayers. 42 The results of their experiments demonstrated that the hydration force has three regimes. The first regime is at large distances, where the force depends on the phase of the lipid bilayer and is mostly due to interactions between undulating membrane surfaces. In the second regime, when the distance between membrane surfaces is in the region 0.4-0.8 nm, the force is independent of the lipid phase, and therefore, according to McIntosh and Simon, the force is indeed due to the presence of water molecules. In this regime there are
Biomolecular simulations of membranes: Physical properties from different force fields
The Journal of Chemical Physics, 2008
Phospholipid force fields are of ample importance for the simulation of artificial bilayers, membranes, and also for the simulation of integral membrane proteins. Here, we compare the two most applied atomic force fields for phospholipids, the all-atom CHARMM27 and the united atom Berger force field, with a newly developed all-atom generalized AMBER force field ͑GAFF͒ for dioleoylphosphatidylcholine molecules. Only the latter displays the experimentally observed difference in the order of the C2 atom between the two acyl chains. The interfacial water dynamics is smoothly increased between the lipid carbonyl region and the bulk water phase for all force fields; however, the water order and with it the electrostatic potential across the bilayer showed distinct differences between the force fields. Both Berger and GAFF underestimate the lipid self-diffusion. GAFF offers a consistent force field for the atomic scale simulation of biomembranes.
Non-periodic Molecular Dynamics simulations of coarse grained lipid bilayer in water
Computers & Mathematics with Applications, 2010
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Examining the Origins of the Hydration Force Between Lipid Bilayers Using All-Atom Simulations
Journal of Membrane Biology, 2010
Using 237 all-atom double bilayer simulations, we examined the thermodynamic and structural changes that occur as a phosphatidylcholine lipid bilayer stack is dehydrated. The simulated system represents a micropatch of lipid multilayer systems that are studied experimentally using surface force apparatus, atomic force microscopy and osmotic pressure studies. In these experiments, the hydration level of the system is varied, changing the separation between the bilayers, in order to understand the forces that the bilayers feel as they are brought together. These studies have found a curious, strongly repulsive force when the bilayers are very close to each other, which has been termed the ''hydration force,'' though the origins of this force are not clearly understood. We computationally reproduce this repulsive, relatively free energy change as bilayers come together and make qualitative conclusions as to the enthalpic and entropic origins of the free energy change. This analysis is supported by data showing structural changes in the waters, lipids and salts that have also been seen in experimental work. Increases in solvent ordering as the bilayers are dehydrated are found to be essential in causing the repulsion as the bilayers come together.
The Journal of Chemical Physics, 2000
The spatial and groupwise distribution of surface tension in a fully hydrated 256 lipid dipalmitoylphosphatidylcholine ͑DPPC͒ bilayer is determined from a 5 ns molecular dynamics simulation by resolving the normal and lateral pressures in space through the introduction of a local virial. The resulting surface tension is separated into contributions from different types of interactions and pairwise terms between lipid headgroups, chains and water. By additionally performing a series of five simulations at constant areas ranging from 0.605 to 0.665 nm 2 ͑each of 6 ns length͒, it is possible to independently resolve the energetic contributions to surface tension from the area dependence of the interaction energies. This also enables us to calculate the remaining entropic part of the tension and the thermal expansivity. Together with the total lateral pressures this yields a full decomposition of surface tension into energetic and entropic contributions from electrostatics, Lennard-Jones and bonded interactions between lipid chains, headgroups and water molecules. The resulting total surface tension in the bilayer is found to be a sum of very large terms of opposing signs, explaining the sensitivity of simulation surface tension to details in force fields. Headgroup and headgroup-water interactions are identified as attractive on average while the chain region wants to expand the bilayer. Both effects are dominated by entropic contributions but there are also substantial energetic terms in the hydrophobic core. The net lateral pressure is small and relatively smooth compared to the individual components, in agreement with experimental observations of DPPC lipids forming stable bilayers.
2020
The spatial and groupwise distribution of surface tension in a fully hydrated 256 lipid dipalmitoylphosphatidylcholine ͑DPPC͒ bilayer is determined from a 5 ns molecular dynamics simulation by resolving the normal and lateral pressures in space through the introduction of a local virial. The resulting surface tension is separated into contributions from different types of interactions and pairwise terms between lipid headgroups, chains and water. By additionally performing a series of five simulations at constant areas ranging from 0.605 to 0.665 nm 2 ͑each of 6 ns length͒, it is possible to independently resolve the energetic contributions to surface tension from the area dependence of the interaction energies. This also enables us to calculate the remaining entropic part of the tension and the thermal expansivity. Together with the total lateral pressures this yields a full decomposition of surface tension into energetic and entropic contributions from electrostatics, Lennard-Jone...
Advances in Polymer Science, 2013
This chapter summarizes several approaches combining theory, simulation and experiment that aim for a better understanding of phenomena in lipid bilayers and membrane protein systems, covering topics such as lipid rafts, membrane mediated interactions, attraction between transmembrane proteins, and aggregation in biomembranes leading to large superstructures such as the light harvesting complex of green plants. After a general overview of theoretical considerations and continuum theory of lipid membranes we introduce different options for simulations of biomembrane systems, addressing questions such as: What can be learned from generic models? When is it expedient to go beyond them? And what are the merits and challenges for systematic coarse graining and quasi-atomistic coarse grained models that ensure a certain chemical specificity?