Skip to main content
SpringerLink
Log in

Molecular dynamics simulation of a phospholipid membrane

  • Published:
European Biophysics Journal Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

MD:

molecular dynamics

DPPC:

dipalmitoylphosphatidylcholine

SPC:

simple point charges

DPPE:

dipalmitoylphosphatidylethanolamine

References

  • Akutsu H (1981) Direct determination by raman scattering of the conformation of the choline group in phospholipid bilayers. Biochemistry 20:7359–7366

    Google Scholar 

  • Akutsu H, Kyogoku Y (1977) Conformational difference in the polar groups of phosphatidylcholine and phosphatidylethanolamine in aqueous phase. Chem Phys Lipids 18:285–303

    Google Scholar 

  • Bareman JP, Klein ML (1990) Collective tilt behavior in dense, substrate-supported monolayers of long-chain molecules: a molecular dynamics study. J Phys Chem 94:5202–5205

    Google Scholar 

  • Berendsen HJC, Postma JPM, Gunsteren WF van, Hermans J (1981) Interaction models for water in relation to protein hydration. In: Pullman B (ed) Intermolecular forces. Reidel, Dordrecht, pp 331–342

    Google Scholar 

  • Berendsen HJC, Postma JPM, Gunsteren WF van, Dinola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81:3684–3690

    Google Scholar 

  • Braganza LF, Worcester DL (1986) Hydrostatic pressure induces hydrocarbon chain interdigitation in single-component phospholipid bilayers. Biochemistry 25:2591–2596

    Google Scholar 

  • Brown MF, Seelig J, Häberlen U (1979) Structural dynamics in phospholipid bilayers from deuterium spin-lattice relaxation time measurements. J Chem Phys 70:5045–5053

    Google Scholar 

  • Büldt G, Gally HU, Seelig A, Seelig J, Zaccai G (1978) Neutron diffraction studies on selectively deuterated phospholipid bilayers. Nature 271:182–184

    Google Scholar 

  • Büldt G, Gally HU, Seelig J (1979) Neutron diffraction studies on phosphatidylcholine model membranes. J Mol Biol 134:673–691

    Google Scholar 

  • Cevc G (1987) How membrane chain melting properties are regulated by the polar surface of the lipid bilayer. Biochemistry 26:6305–6310

    Google Scholar 

  • Chandrasekhar I(1992) In: Gaber BP, Easwaran KRK (eds) Biomembrane structure and function. Adenine Press, New York, p 353

    Google Scholar 

  • Chapman D, Williams RW, Ladbrooke BD (1967) Physical studies of phospholipids. VI. Thermotropic and lyotropic mesomorphism of some 1,2-diacylphosphatidylcholines (lecithins). Chem Phys Lipids 1:445–475

    Google Scholar 

  • Egberts E (1988) Molecular dynamics simulation of multibilayer membranes. Ph.D.Thesis, Rijksuniversiteit Groningen

  • Egberts E, Berendsen HJC (1988) Molecular dynamics simulation of a smectic liquid crystal with atomic detail. J Chem Phys 89:3718–3732

    Google Scholar 

  • Fahey PF, Webb WW (1978) Lateral diffusion in phospholipid bilayer membranes and multilamellar liquid crystals. Biochemistry 17:3046–3053

    Google Scholar 

  • Frischleder H (1980) Quantum-chemical and empirical calculations on phospholipids. VII The conformational behavior of the phosphatidylcholine headgroup in layer systems. Chem Phys Lipids 27:83–92

    Google Scholar 

  • Frischleder H, Peinel G (1982) Quantum-chemical and statistical calculations on phospholipids. Chem Phys Lipids 30:121–158

    Google Scholar 

  • Gally HU, Niederberger W, Seelig J (1975) Conformation and motion of the choline head group in bilayers of dipalmitoyl-e-snphosphatidylcholine. Biochemistry 14:3647–3652

    Google Scholar 

  • Gruen DWR (1981) A mean-field model of the alkane-saturated lipid bilayer above the phase transition. I. Development of the model. Biophys J 33:149–166

    Google Scholar 

  • Gunsteren WF van, Berendsen HJC (1977) Algorithms for macromolecular dynamics and constraint dynamics. Mol Phys 34:1311–1327

    Google Scholar 

  • Gunsteren WF van, Berendsen HJC (1987) Groningen molecular simulation (GROMOS) library manual, Biomos, Nijenborgh 4, 9747 AG Groningen, The Netherlands

    Google Scholar 

  • Hauser H, Pascher I, Pearson RH, Sundell S (1981) Preferred conformation and molecular packing of phosphatidylethanolamine and phosphatidylcholine. Biochim Biophys Acta 650:21–51

    Google Scholar 

  • Hockney RW Eastwood JW (1981) Computer simulation using particles. McGraw-Hill, New York

    Google Scholar 

  • Horvath LI, Cirak J, Vigh L (1980) Relation of raman order parameters to spin labeling parameters. Chem Phys Lipids 27:237–250

    Google Scholar 

  • Inoko Y, Mitsui T (1978) Structural parameters of dipalmitoyl phosphatidylcholine lamellar phases and bilayer phase transitions. J Phys Soc Japan 44:1918–1924

    Google Scholar 

  • Janiak MJ, Small DM, Shipley GG (1976) Nature of the thermal pretransiton of synthetic phospholipids: dimyristoyl- and dipalmitoyllecithin. Biochemistry 15:4575–4580

    Google Scholar 

  • Janiak MJ, Small DM, Shipley GG (1979) Temperature and compositional dependence of the structure of hydrated dimyristoyl lecithin. J Biol Chem 254:6068–6078

    Google Scholar 

  • Jönsson B, Edholm O, Teleman O (1986) Molecular dynamics simulations of a sodium octanoate micelle in aqueous solution. J Chem Phys 85:2259–2271

    Google Scholar 

  • Levine YK, Wilkins MHF (1971) Structure of oriented lipid bilayers. Nature New Biol 230:69–72

    Google Scholar 

  • Lewis BA, Engelman DM (1983) Lipid bilayer thickness varies linearly with acyl chain length in fluid phosphatidylcholine vesicles. J Mol Biol 166:211–217

    Google Scholar 

  • Lewis RNAH, Mannock DA, McElhaney RN (1989) Effect of fatty acyl chain length and structure on the lamellar gel to liquid-crystalline and lamellar to reversed hexagonal phase transitions of aqueous phosphatidylethanolamine dispersions. Biochemistry 28:541–548

    Google Scholar 

  • Lindblom G, Wennerström H (1977) Biological and model membranes studies by nuclear magnetic resonance of spin one half nuclei. Q Rev Biophys 10:67–96

    Google Scholar 

  • Lis LJ, McAlister M, Fuller N, Rand RP, Parsegian VA (1982) Interactions between neutral phospholipid bilayer membranes. Biophys J 37:657–665

    Google Scholar 

  • London RE, Walker TE, Wilson DM, Matwiyoff NA (1979) Application of doubly decoupled carbon-13{proton, nitrogen-14-NMR spectroscopy to studies of phospholipids}. Chem Phys Lipids 25:7–14

    Google Scholar 

  • Loof H de, Harvey SC, Segrest JP, Pastor RW (1991) Mean field stochastic boundary molecular dynamics simulation of a phospholipid in a membrane. Biochemistry 30:2099–2113

    Google Scholar 

  • Marrink SJ, Berkowitz M, Berendsen HJC (1993) Molecular dynamics simulation of a membrane/water interface: the ordering of water and its relation to the hydration force. Langmuir (in press)

  • Marsh D (1974) Statistical mechanics of the fluidity of phospholipid bilayers and membranes. J Membr Biol 18:145–162

    Google Scholar 

  • McConnell HM, Devaux P, Scandella C (1971) In: Fox CF (ed) Membrane research. Academic Press, New York

    Google Scholar 

  • Meier P, Ohmes E, Kothe G (1986) Multipulse dynamic nuclear magnetic resonance of phospholipid membranes. J Chem Phys 85:3598–3614

    Google Scholar 

  • Mendelsohn R, Davies MA, Brauner JW, Schuster HF, Dluhy RA (1989) Quantitative determination of conformational disorder in the acyl chains of phospholipid bilayers by infrared spectroscopy. Biochemistry 28:8934–8939

    Google Scholar 

  • Meraldi JP, Schlitter J (1981) A statistical mechanical treatment of fatty acyl chain order in phospholipid bilayers and correlation with experimental data. B. Dipalmitoyl-3-sn-phosphatidylcholine. Biochim Biophys Acta 645:193–210

    Google Scholar 

  • Moller MA, Tildesley DJ, Kim KS, Quirke N (1991) Molecular dynamics simulation of a Langmuir-Blodgett film. J Chem Phys 94:8390–8401

    Google Scholar 

  • Nagle JF, Wiener MC (1988) Structure of fully hydrated bilayer dispersions. Biochim Biophys Acta 942:1–10

    Google Scholar 

  • Phillips MC, Williams RM, Chapman D (1968) Hydrocarbon chain motions in lipid liquid crystals. Chem Phys Lipids 3:234–244

    Google Scholar 

  • Pink DA, Green TJ, Chapman D (1980) Raman scattering in bilayers of saturated phosphatidylcholines. Experiment and theory. Biochemistry 19:349–356

    Google Scholar 

  • Ploeg P van der, Berendsen HJC (1982) Molecular dynamics simulation of a bilayer membrane. J Chem Phys 76:3271–3276

    Google Scholar 

  • Ploeg P van der, Berendsen HJC (1983) Molecular dynamics of a bilayer membrane. Mol Phys 49:233–248

    Google Scholar 

  • Reiss-Husson J (1967) Structure des phases liquide-cristallines de différents phospholipides, monoglycérides, sphingolipides, anhydres on en presence d'eau. J Mol Biol 25:363–382

    Google Scholar 

  • Rubinstein JLR, Smith BA, McConnell HM (1979) Lateral diffusion in binary mixtures of cholesterol and phosphatidylcholines. Proc Natl Acad Sci, USA 76:15–18

    Google Scholar 

  • Ruocco MJ, Shipley GG (1982) Characterization of the sub-transition of hydrated dipalmitoylphosphatidylcholine bilayers. Biochim Biophys Acta 691:309–320

    Google Scholar 

  • Ryckaert JP, Bellemans A (1975) Molecular dynamics of liquid n-butane near its boiling point. Chem Phys Lett 30:123–125

    Google Scholar 

  • Ryckaert JP, Bellemans A (1978) Faraday Discuss Chem. Soc. 66:95

    Google Scholar 

  • Ryckaert JP, Ciccotti G, Berendsen HJC (1977) Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J Comp Phys 23:327–341

    Google Scholar 

  • Schindler H, Seelig J (1975) Deuterium order parameters in relation to thermodynamic properties of a phospholipid bilayer. A statistical mechanical interpretation. Biochemistry 14:2283–2278

    Google Scholar 

  • Seelig J (1977) Deuterium magnetic resonance: theory and application to lipid membranes. Q Rev Biophys 10:353–418

    Google Scholar 

  • Seelig J (1978) Nuclear magnetic resonance and the head group structure of phospholipids in membranes. Biochim Biophys Acta 515:105–140

    Google Scholar 

  • Seelig J, Gaily HU (1976) Investigation of phosphatidylethanolamine bilayers by deuterium and phosphorus-31 nuclear magnetic resonance. Biochemistry 15:5199–5204

    Google Scholar 

  • Seelig A, Seelig J (1974) The dynamic structure of fatty acyl chains in a phospholipid bilayer measured by deuterium magnetic resonance. Biochemistry 13:4839–4845

    Google Scholar 

  • Seelig A, Seelig J (1975) Bilayers of dipalmitoyl-3-sn-phosphatidylcholine conformational differences between the fatty acyl chains. Biochim Biophys Acta 406:1–5

    Google Scholar 

  • Seelig J, Seelig A (1980) Lipid conformation in model membranes and biological membranes. Q Rev Biophys 13:19–61

    Google Scholar 

  • Seelig J, Gaily HU, Wohlgemuth R (1977) Orientation and flexibility of the choline head group in phosphatidylcholine bilayers. Biochim Biophys Acta 467:109–119

    Google Scholar 

  • Sheats JR, McConnell HM (1978) A photochemical technique for measuring lateral diffusion of spin-labeled phospholipids in membranes. Proc Natl Acad Sci, USA 75:4661–4663

    Google Scholar 

  • Smith BA, McConnell HM (1978) Determination of molecular motion in membranes using periodic pattern photobleaching. Proc Natl Acad Sci, USA 15:2759–2763

    Google Scholar 

  • Sundaralingam M (1972) Molecular structures and conformations of the phospholipids and sphingomyelins. Ann NY Acad Sci, USA 195:324–355

    Google Scholar 

  • Tamm LK, Seelig J (1983) Lipid solvation of cytochrome c oxidase. Deuterium, nitrogen-14, and phosphorus-31 nuclear magnetic resonance studies on the phosphocholine head group and on cis-unsaturated fatty acyl chains. Biochemistry 22:1474–1483

    Google Scholar 

  • Tardieu A, Luzzati V, Reman FC (1973) Structure and polymorphism of the hydrocarbon chains of lipids: a study of lecithinwater phases. J Mol Biol 75:711–733

    Google Scholar 

  • Tenchov BG, Lis LJ, Quinn PJ (1987) Mechanism and kinetics of the subtransition in hydrated L-lipalmitoylphosphatidylcholine. Biochim Biophys Acta 897:143–151

    Google Scholar 

  • Träuble H, Haynes DH (1974) Volume change in lipid bilayer lamellae at the crystalline-liquid crystalline phase transition. Chem Phys Lipids 7:324

    Google Scholar 

  • Ulmius J, Wennerström H, Lindblom G, Arvidson G (1977) Deuteron nuclear magnetic resonance studies of phase equilibria in a lecithin-water system. Biochemistry 16:5742–5745

    Google Scholar 

  • Vaz WLC, Stümpel J, Hallmann D, Gambacorta A, Rosa M de (1987) Bounding fluid viscosity and translational diffusion in a fluid lipid bilayer. Eur Biophys J 15:111–115

    Google Scholar 

  • Wiener MC, White SH (1992a) Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. II. Distribution and packing of terminal methyl groups. Biophys J 61:428–433

    Google Scholar 

  • Wiener MC, White SH (1992b) Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. I. Complete structure. Biophys J 61:434

    Google Scholar 

  • Wu E, Jacobson K, Papahadjopoulos D (1977) Lateral diffusion in phospholipid multibilayers measured by fluorescence recovery after photobleaching. Biochemistry 16:3936–3941

    Google Scholar 

  • Zaccai G, Büldt G, Seelig A, Seelig J (1979) Neutron diffraction studies on phosphatidylcholine model membranes. II Chain conformation and segmental disorder. J Mol Biol 134:693–706

    Google Scholar 

  • Zaccai G, Blasie JK, Schoenborn BP (1980) Neutron diffraction studies on the location of water in lecithin bilayer model membranes. Proc Natl Acad Sci, USA 72:376–380

    Google Scholar 

Download references

Author information

Author notes

  1. Egbert Egberts

    Present address: Philips Research Laboratories, 5600 JA, P.O. Box 80000, Eindhoven, The Netherlands

Authors and Affiliations

  1. Department of Biophysical Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands

    Egbert Egberts, Siewert-Jan Marrink & Herman J. C. Berendsen

Authors
  1. Egbert Egberts
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Siewert-Jan Marrink
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Herman J. C. Berendsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Correspondence to: H. J. C. Berendsen

Rights and permissions

Reprints and permissions

About this article

Cite this article

Egberts, E., Marrink, SJ. & Berendsen, H.J.C. Molecular dynamics simulation of a phospholipid membrane. Eur Biophys J 22, 423–436 (1994). https://doi.org/10.1007/BF00180163

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00180163

Key words

Search

Navigation