Molecular Dynamics Simulations of Lipid Bilayers: Major Artifacts Due to Truncating Electrostatic Interactions

Patra, Michael; Karttunen, Mikko; Hyvönen, M.; Falck, Emma; Lindqvist, Per-Arne; Vattulainen, Ilpo

doi:10.1016/s0006-3495(03)75094-2

Cited by 388 publications

(463 citation statements)

References 61 publications

(71 reference statements)

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“…The detailed calculation procedure was similar to that reported previously for lipid mixtures [32][33][34][35] . To prevent the calculation from overestimating the area for smaller size CHOL or underestimating the area for larger molecules POPC and POPA, we also adopted the previous published method to generate Voronoi tessellation 33 .…”

Section: Discussionmentioning

confidence: 84%

Molecular Dynamics Simulations of Ternary Membrane Mixture: Phosphatidylcholine, Phosphatidic Acid, and Cholesterol

et al. 2007

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A ternary mixture of 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC), 1-palmitoyl-2-oleoyl phosphatidic acid (POPA), and cholesterol (CHOL) works effectively for a functional conformation of nicotinic acetylcholine receptor (nAChR) that can undergo agonist-induced conformation changes, but POPC alone can stabilize only a desensitized state of nAChR. To gain insights into the lipid mixture that have strong impact to nAChR functions, we performed more than 50-ns all atom molecular dynamic (MD) simulations at 303 K on a fully hydrated bilayer consisting of 240 POPC, 80 POPA, and 80 CHOL (3:1:1). The MD simulation revealed various interactions between different types of molecular pairs that ultimately regulated lipid organization. The heterogeneous interactions among three different constituents resulted in a broad spectrum of lipid properties, including extensive distribution of average area per lipids and varied lipid ordering as a function of lipid closeness to CHOL. Higher percentage of POPA than POPC had close association with CHOL, which coincided with relatively higher ordering of POPA molecules in their acyl chains near lipid head groups. Lower fraction of gauche dihedrals was also found in the same region of POPA. Although the CHOL molecules had the effects on the enhancement of surrounding lipid order, relatively low lipid order parameters and high fraction of gauche bonds were observed in the ternary mixture. Collectively, these results suggest that the dynamical structure of the ternary system could be determinant for a functional nAChR.

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Section: Discussionmentioning

confidence: 84%

Molecular Dynamics Simulations of Ternary Membrane Mixture: Phosphatidylcholine, Phosphatidic Acid, and Cholesterol

et al. 2007

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“…35 The Lennard-Jones interactions were cut off at 1 nm without shift or switch functions. Since truncation of electrostatic interactions is known to lead to pronounced artifacts in simulations of lipid bilayers, [36][37][38] the long-range interactions were handled using the particle-mesh Ewald (PME) method. 39,40 All simulations were performed in the NpT ensemble at 323 K and 1 bar.…”

Section: Model and Simulation Detailsmentioning

confidence: 99%

Effect of Monovalent Salt on Cationic Lipid Membranes As Revealed by Molecular Dynamics Simulations

Gurtovenko

Miettinen²,

Karttunen³

et al. 2005

J. Phys. Chem. B

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An atomic-scale understanding of cationic lipid membranes is required for development of gene delivery agents based on cationic liposomes. To address this problem, we recently performed molecular dynamics (MD) simulations of mixed lipid membranes comprised of cationic dimyristoyltrimethylammonium propane (DMTAP) and zwitterionic dimyristoylphosphatidylcholine (DMPC) (Biophys. J. 2004, 86, 3461-3472). Given that salt ions are always present under physiological conditions, here we focus on the effects of monovalent salt (NaCl) on cationic (DMPC/DMTAP) membranes. Using atomistic MD simulations, we found that saltinduced changes in membranes depend strongly on their composition. When the DMTAP mole fraction is small (around 6%), the addition of monovalent salt leads to a considerable compression of the membrane and to a concurrent enhancement of the ordering of lipid acyl chains. That is accompanied by reorientation of phosphatidylcholine headgroups in the outward normal direction and slight changes in electrostatic properties. We attribute these changes to complexation of DMPC lipids with Na + ions which penetrate deep into the membrane and bind to the carbonyl region of the DMPC lipids. In contrast, at medium and high molar fractions of cationic DMTAP (50 and 75%) a substantial positive surface charge density of the membranes prevents the binding of Na + ions, making such membranes almost insensitive to monovalent salt. Finally, we compare our results to the Poisson-Boltzmann theory. With the exception of the immediate vicinity of the bilayer plane, we found excellent agreement with the theory. This is as expected since unlike in the theoretical description the surface is now structured due to its atomic scale nature.

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“…In the past, there has been much work to include the effects of Coulombic interactions [5,6,7,8,9,10,11,12] without performing the computationally costly Ewald summations. Present day computational resources allow one to treat electrostatics properly [13] and in, e.g., the case of lipid bilayers, this is a very important matter [14].…”

Section: Introductionmentioning

confidence: 99%

Systematic comparison of force fields for microscopic simulations of NaCl in aqueous solutions: Diffusion, free energy of hydration, and structural properties

Patra¹,

Karttunen²

2004

J Comput Chem

208

209

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In this paper we compare different force fields that are widely used (Gromacs, Charmm-22/xPlor, Charmm-27, Amber-1999, OPLS-AA) in biophysical simulations containing aqueous NaCl. We show that the uncertainties of the microscopic parameters of, in particular, sodium and, to a lesser extent, chloride translate into large differences in the computed radial-distribution functions. This uncertainty reflects the incomplete experimental knowledge of the structural properties of ionic aqueous solutions at finite molarity. We discuss possible implications on the computation of potential of mean force and effective potentials.

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Molecular Dynamics Simulations of Lipid Bilayers: Major Artifacts Due to Truncating Electrostatic Interactions

Cited by 388 publications

References 61 publications

Molecular Dynamics Simulations of Ternary Membrane Mixture: Phosphatidylcholine, Phosphatidic Acid, and Cholesterol

Molecular Dynamics Simulations of Ternary Membrane Mixture: Phosphatidylcholine, Phosphatidic Acid, and Cholesterol

Effect of Monovalent Salt on Cationic Lipid Membranes As Revealed by Molecular Dynamics Simulations

Systematic comparison of force fields for microscopic simulations of NaCl in aqueous solutions: Diffusion, free energy of hydration, and structural properties

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