Time Scales of Lipid Dynamics and Molecular Dynamics

  • Richard W. Pastor
  • Scott E. Feller


It is finally possible to carry out a molecular dynamics (MD) computer simulation of a protein or peptide in a lipid bilayer. Simulation programs with reasonable potential energy parameters are readily available, computer workstations are affordable, and plausible initial conditions can be constructed by combining the polypeptide with lipid configurations taken from simulations of pure lipid bilayers. Clearly, there are many questions to ask. Does the protein somehow order the nearby lipids or perturb the water structure at the head-group/solution interface? If the membrane contains a mixture of lipids, do some selectively condense around the protein? What are the lateral diffusion constants and isomerization rates for the lipids and protein, and are they perturbed from the pure state? These sorts of effects might be important to the protein’s function, or they might modulate the rate that substrates pass through the bilayer. They could change the interfacial tension, making it easier for the membrane to bend or even fuse with another. A peptide with potential drug applications might disrupt the bilayer, aggregate to form channels, or bind to a membrane protein.


Molecular Dynamic Simulation Lipid Bilayer Brownian Dynamic Brownian Dynamic Simulation Lipid Dynamics 
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  1. Allen MP, Tildesley DJ (1987): Computer Simulation of Liquids. Oxford: ClarendonGoogle Scholar
  2. Andersen HC (1980): Molecular dynamics simulations at constant pressure and/or temperature. J Chem Phys 72:2384–2393CrossRefGoogle Scholar
  3. Berne BJ, Pecora R (1976): Dynamic Light Scattering. New York: Wiley-InterscienceGoogle Scholar
  4. Brasseur R, ed. (1990): Molecular Description of Biological Membrane Components by Computer Aided Conformational Analysis, Vol. I. Boca Raton: CRC PressGoogle Scholar
  5. Brooks CL, Pettitt BM, Karplus M (1988): Proteins: A Theoretical Perspective of Dynamics Structure, and Thermodynamics. New York: Wiley-InterscienceGoogle Scholar
  6. Brown MF, Ribeiro AA, Williams GD (1983): New view of lipid bilayer dynamics from 2H and 13C relaxation time measurements. Proc Natl Acad Sei USA 80:4325–4329CrossRefGoogle Scholar
  7. Brown ML, Venable RM, Pastor RW (1995): Method for characterizing transition con-certedness from polymer dynamics computer simulations. Biopolymers 35:31–46PubMedCrossRefGoogle Scholar
  8. Cevc G, Marsh D (1987): Phospholipid Bilayers. New York:Wiley-InterscienceGoogle Scholar
  9. Chandler D (1977): Statistical mechanics of isomerization dynamics in liquids and the transition state approximation. J Chem Phys 68:2959–2970CrossRefGoogle Scholar
  10. Cherry RJ (1979): Rotational and lateral diffusion of membrane proteins. Biochem Bio-phys Acta 559:289–327Google Scholar
  11. Crow EL, Gardner RS (1959): Confidence intervals for the expectation of a Poisson variable. Biometrika 46:441–453Google Scholar
  12. de Gennes PG (1974): The Physics and Chemistry of Liquid Crystals. Oxford: ClarendonGoogle Scholar
  13. DeGroot MH (1975): Probability and Statistics. Reading, MA: Addison-WesleyGoogle Scholar
  14. De Loof H, Segrest JP, Harvey S, Pastor RW (1991): Mean field stochastic boundary molecular dynamics simulation of a phospholipid in a membrane. Biochemistry 30:2099–2113PubMedCrossRefGoogle Scholar
  15. Ermak DL (1975): A computer simulation of charged particles in solution. I. Technique and equilibrium properties. J Chem Phys 62:4189–4196CrossRefGoogle Scholar
  16. Feller W (1950): An Introduction to Probability Theory and its Applications. New York: John Wiley and SonsGoogle Scholar
  17. Feller SE, Zhang Y, Pastor RW, Brooks BR (1995a): Constant pressure molecular dynamics simulation: the Langevin piston method. J Chem Phys 103:4613–4621CrossRefGoogle Scholar
  18. Feller SE, Zhang Y, Pastor RW (1995b): Computer simulations of liquid/liquid interfaces. II. Surface tension-area dependence of a bilayer and monolayer. J Chem Phys 103:10267–10276CrossRefGoogle Scholar
  19. Galla H-J, Hartmann W, Theilen U, Sackmann E (1979): On two-dimensional passive ranndom walks in lipid bilayers and fluid pathways in biomembranes. J Membrane Biol 48:215–236CrossRefGoogle Scholar
  20. Glaser M (1993): Lipid domains in biological membranes. Current Opinion in Structural Biology 3:475–481CrossRefGoogle Scholar
  21. Hanggi P, Talkner P, Borkovec M (1990): Reaction-rate theory: fifty years after Kramers. Rev Mod Phys. 62:251–341CrossRefGoogle Scholar
  22. Hardy BH, Pastor RW (1994): Conformational sampling of hydrocarbon and lipid chains in an ordering potential. J Comput Chem 15:208–226CrossRefGoogle Scholar
  23. Hoel PG, Port SC, Stone CJ (1972): Introduction to Stochastic Process. Boston: Houghton MifflinGoogle Scholar
  24. Hoover WG (1985): Canonical dynamics: equilibrium phase-space distributions. Phys Rev A 31:1695–1697PubMedCrossRefGoogle Scholar
  25. Katsaras J (1995): Structure of the subgel (Lc’) and gel (L β’ ) phases of oriented dipalmi-toylphosphatidylcholine multilayers. J Phys Chem 99:4141–4147CrossRefGoogle Scholar
  26. Lipari G, Szabo A (1980): Effect of librational motion on fluorescence depolarization and nuclear magnetic resonance relaxation in macromolecules and membranes. Biophys J 30:489–506PubMedCrossRefGoogle Scholar
  27. Marqusee JA, Warner M, Dill KA (1984): Frequency dependence of NMR spin lattice relaxation in bilayer membranes. J Chem Phys 81:6404–6405CrossRefGoogle Scholar
  28. Martyna GJ, Tobias DL, Klein ML (1994): Constant pressure molecular dynamics algorithms. J Phys Chem. 101:4177–4189CrossRefGoogle Scholar
  29. Nagle JF (1993): Area/lipid of bilayers from NMR. Biophys J 64:1476–1481PubMedCrossRefGoogle Scholar
  30. Nose S (1984): A molecular dynamics method for simulations in the canonical ensemble. Mol Phys 52:255–268CrossRefGoogle Scholar
  31. Nose S, Klein ML (1983): Constant pressure molecular dynamics for molecular systems. Mol Phys 50:1055–1076CrossRefGoogle Scholar
  32. Parrinello M, Rahman A (1981): Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 14:7182–7190CrossRefGoogle Scholar
  33. Pascher I, Lundmark M, Nyholm, P-G, Sundeil S (1992): Crystal structures of membrane lipids. Biochem et Biophys Acta 1113:329–373Google Scholar
  34. Pastor RW (1994a): Techniques and applications of Langevin dynamics simulations. In The Molecular Dynamics of Liquid Crystals Luckhurst GR and Veracini CA, eds. Dordrecht: Kluwer Academic PublishersGoogle Scholar
  35. Pastor RW (1994b): Molecular dynamics and Monte Carlo simulations of lipid bilayers. Curr Opin Struct Biol 4:486–492CrossRefGoogle Scholar
  36. Pastor RW, Venable RM (1993): Molecular and stochastic dynamics simulation of lipid membranes. In: Computer Simulation of Biomolecular Systems: Theoretical and Experimental Applications, van Gunsteren WF, Weiner PK, Wilkinson AK, eds. Leiden: ESCOM Science PublishersGoogle Scholar
  37. Pastor RW, Venable RM, Karplus M (1988a): Brownian dynamics simulation of a lipid chain in a membrane bilayer. J Chem Phys 89:1112–1227CrossRefGoogle Scholar
  38. Pastor RW, Venable RM, Karplus M, Szabo A (1988b): A simulation based model of NMR T 1 Relaxation in lipid bilayer vesicles. J Chem Phys 89:1128–1140CrossRefGoogle Scholar
  39. Petersen NO, Chan SI (1977): More on the motional state of lipid bilayer membranes: interpretation of order parameters obtained from nuclear magnetic resonance experiments. Biochemistry 16:2657–2667PubMedCrossRefGoogle Scholar
  40. Rahman A (1964): Correlations in the motion of atoms in liquid argon. Phys Rev 136A:405–411CrossRefGoogle Scholar
  41. Rand RP, Parsegian VA (1989): Hydration forces between phospholipid bilayers. Biochem Biophys Acta 998:351–376Google Scholar
  42. Rommel E, Noack F, Meier P, Kothe G (1988): Proton spin relaxation dispersion studies of phospholipid membranes. J Phys Chem 92:2981–2987CrossRefGoogle Scholar
  43. Schulten K, Schulten Z, Szabo A (1981): Dynamics of reactions involving diffusive barrier crossing. J Chem Phys 74:4426–4432CrossRefGoogle Scholar
  44. Seelig J, Mcdonald PM (1987): Phospholipids and proteins in biological membranes. 2H NMR as a method to study structure, dynamics and interactions. Ace Chem Res 20:221–228CrossRefGoogle Scholar
  45. Seelig J, Seelig A (1980): Lipid conformation in model membranes and biological membranes. Quart Rev of Biophys 13:19–61CrossRefGoogle Scholar
  46. Skolnick J, Helfand E (1980): Kinetics of conformational transitions in chain molecules. J Chem Phys 72:5489–5500CrossRefGoogle Scholar
  47. Small DM (1986): The Physical Chemistry of Lipids. New York: PlenumGoogle Scholar
  48. Smith GS, Sirota EB, Safinya CR, Piano RJ, Clark NA (1990): X-ray structural studies of freely suspended ordered hydrated DMPC miltimembrane films. J Chem Phys 92:4519–4529CrossRefGoogle Scholar
  49. Snyder RG (1992): Chain conformation for the direct calculation of the Raman spectra of the liquid alkanes C12–C20. Faraday Trans 13:1823–1833CrossRefGoogle Scholar
  50. Stouch TR (1993): Lipid membrane structure and dynamics studied by all-atom molecular dynamics simulations of hydrated phospholipid bilayers. Mol Sim 10:335–362CrossRefGoogle Scholar
  51. Sundaralingam M (1972): Molecular structures and conformations of the phospholipids and sphingomyelins. Ann N Acad Sei 195:324–355CrossRefGoogle Scholar
  52. Szabo A (1984): Theory of fluorescence depolarization in macromolecules and membranes. J Chem Phys 81:150–167CrossRefGoogle Scholar
  53. Tanford C (1961) Physical Chemistry of Macromolecules. New York: John Wiley and SonsGoogle Scholar
  54. Tristram-Nagle S, Zhang R, Suter RM, Worthington CR, Sun WJ, Nagle JF (1993): Measurement of chain tilt angle in fully hydrated bilayers of gel phase lecithns. Biophys 7 64:1097–1109CrossRefGoogle Scholar
  55. van Gunsteren WF, Weiner PK, Wilkinson AK, eds (1993): Computer Simulation of Biomolecular Systems: Theoretical and Experimental Applications. Leiden: ESCOM Science PublishersGoogle Scholar
  56. Vaz WLC, Almeida PF (1991): Miscoscopic versus macroscopic diffusion in one-component fluid phase bilayer membranes. Biophys J 60:1553–1554PubMedCrossRefGoogle Scholar
  57. Venable RM, Zhang Y, Hardy BJ, Pastor RW (1993): Molecular dynamics simulations of a lipid bilayer and of hexadecane: an investigation of membrane fluidity. Science 262:223–226PubMedCrossRefGoogle Scholar
  58. Wang CC, Pecora R (1980): Time correlation functions for restricted rotational diffusion. J Chem Phys 72:5333–5340CrossRefGoogle Scholar
  59. Wax N (1954): Noise and Stochastic Processes. New York: DoverGoogle Scholar
  60. Williams DE, Stouch TR (1993): Characterization of force fields for lipid molecules: applications to crystal structures. J Comp Chem 14:1066–1076CrossRefGoogle Scholar
  61. Woolf TB, Roux B (1994): Molecular dynamics simulation of the gramicidin channel in a phospholipid bilayer. Proc Natl Acad Sci (USA) 91:11631–11635CrossRefGoogle Scholar
  62. Yellin N, Levin I (1977): Hydrocarbon chain trans-gauche isomerization in phospholipid bilayer gel assemblies. Biochemistry 16:642–647PubMedCrossRefGoogle Scholar
  63. Zhang Y, Pastor RW (1994): A comparison of methods for computing transition rates from molecular dynamics simulation. Mol. Sim. 13:25–38CrossRefGoogle Scholar
  64. Zhang Y, Feller SE, Brooks BR, Pastor RW (1995): Computer simulations of liquid/liquid interfaces. I. Theory and application to octane/water. J Chem Phys 103:10252–10266CrossRefGoogle Scholar
  65. Zwanzig R, Ailawadi NK (1969): Statistical error due to finite time averaging in computer experiments. Phys Rev 182:280–283CrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 1996

Authors and Affiliations

  • Richard W. Pastor
  • Scott E. Feller

There are no affiliations available

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