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. 1999 Apr;76(4):1929–1938. doi: 10.1016/S0006-3495(99)77352-2

Simulation study of a gramicidin/lipid bilayer system in excess water and lipid. I. Structure of the molecular complex.

S W Chiu 1, S Subramaniam 1, E Jakobsson 1
PMCID: PMC1300169  PMID: 10096891

Abstract

This paper reports on a simulation of a gramicidin channel inserted into a fluid phase DMPC bilayer with 100 lipid molecules. Two lipid molecules per leaflet were removed to insert the gramicidin, so the resulting preparation had 96 lipid molecules and 3209 water molecules. Constant surface tension boundary conditions were employed. Like previous simulations with a lower lipid/gramicidin ratio (Woolf, T. B., and B. Roux. 1996. Proteins: Struct., Funct., Genet. 24:92-114), it is found that tryptophan-water hydrogen bonds are more common than tryptophan-phospholipid hydrogen bonds. However, one of the tryptophan NH groups entered into an unusually long-lived hydrogen bonding pattern with two glycerol oxygens of one of the phospholipid molecules. Comparisons were made between the behavior of the lipids adjacent to the channel with those farther away. It was found that hydrocarbon chains of lipids adjacent to the channel had higher-order parameters than those farther away. The thickness of the lipid bilayer immediately adjacent to the channel was greater than it was farther away. In general, the lipids adjacent to the membrane had similar orientations to those seen by Woolf and Roux, while those farther away had similar orientations to those pertaining before the insertion of the gramicidin. A corollary to this observation is that the thickness of the hydrocarbon region adjacent to the gramicidin was much thicker than what other studies have identified as the "hydrophobic length" of the gramicidin channel.

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Selected References

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  1. Burkhart B. M., Li N., Langs D. A., Pangborn W. A., Duax W. L. The conducting form of gramicidin A is a right-handed double-stranded double helix. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):12950–12955. doi: 10.1073/pnas.95.22.12950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chiu S. W., Clark M., Balaji V., Subramaniam S., Scott H. L., Jakobsson E. Incorporation of surface tension into molecular dynamics simulation of an interface: a fluid phase lipid bilayer membrane. Biophys J. 1995 Oct;69(4):1230–1245. doi: 10.1016/S0006-3495(95)80005-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chiu S. W., Jakobsson E., Subramaniam S., McCammon J. A. Time-correlation analysis of simulated water motion in flexible and rigid gramicidin channels. Biophys J. 1991 Jul;60(1):273–285. doi: 10.1016/S0006-3495(91)82049-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elliott J. R., Needham D., Dilger J. P., Haydon D. A. The effects of bilayer thickness and tension on gramicidin single-channel lifetime. Biochim Biophys Acta. 1983 Oct 26;735(1):95–103. doi: 10.1016/0005-2736(83)90264-x. [DOI] [PubMed] [Google Scholar]
  5. Feller S. E., Pastor R. W. On simulating lipid bilayers with an applied surface tension: periodic boundary conditions and undulations. Biophys J. 1996 Sep;71(3):1350–1355. doi: 10.1016/S0006-3495(96)79337-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Girshman J., Greathouse D. V., Koeppe R. E., 2nd, Andersen O. S. Gramicidin channels in phospholipid bilayers with unsaturated acyl chains. Biophys J. 1997 Sep;73(3):1310–1319. doi: 10.1016/S0006-3495(97)78164-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Goulian M., Mesquita O. N., Fygenson D. K., Nielsen C., Andersen O. S., Libchaber A. Gramicidin channel kinetics under tension. Biophys J. 1998 Jan;74(1):328–337. doi: 10.1016/S0006-3495(98)77790-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Helfrich P., Jakobsson E. Calculation of deformation energies and conformations in lipid membranes containing gramicidin channels. Biophys J. 1990 May;57(5):1075–1084. doi: 10.1016/S0006-3495(90)82625-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hladky S. B., Haydon D. A. Discreteness of conductance change in bimolecular lipid membranes in the presence of certain antibiotics. Nature. 1970 Jan 31;225(5231):451–453. doi: 10.1038/225451a0. [DOI] [PubMed] [Google Scholar]
  10. Hu W., Lazo N. D., Cross T. A. Tryptophan dynamics and structural refinement in a lipid bilayer environment: solid state NMR of the gramicidin channel. Biochemistry. 1995 Oct 31;34(43):14138–14146. doi: 10.1021/bi00043a019. [DOI] [PubMed] [Google Scholar]
  11. Huang H. W. Deformation free energy of bilayer membrane and its effect on gramicidin channel lifetime. Biophys J. 1986 Dec;50(6):1061–1070. doi: 10.1016/S0006-3495(86)83550-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jähnig F. What is the surface tension of a lipid bilayer membrane? Biophys J. 1996 Sep;71(3):1348–1349. doi: 10.1016/S0006-3495(96)79336-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ketchem R. R., Hu W., Cross T. A. High-resolution conformation of gramicidin A in a lipid bilayer by solid-state NMR. Science. 1993 Sep 10;261(5127):1457–1460. doi: 10.1126/science.7690158. [DOI] [PubMed] [Google Scholar]
  14. Ketchem R. R., Lee K. C., Huo S., Cross T. A. Macromolecular structural elucidation with solid-state NMR-derived orientational constraints. J Biomol NMR. 1996 Jul;8(1):1–14. doi: 10.1007/BF00198135. [DOI] [PubMed] [Google Scholar]
  15. Ketchem R., Roux B., Cross T. High-resolution polypeptide structure in a lamellar phase lipid environment from solid state NMR derived orientational constraints. Structure. 1997 Dec 15;5(12):1655–1669. doi: 10.1016/s0969-2126(97)00312-2. [DOI] [PubMed] [Google Scholar]
  16. Koeppe R. E., 2nd, Anderson O. S. Engineering the gramicidin channel. Annu Rev Biophys Biomol Struct. 1996;25:231–258. doi: 10.1146/annurev.bb.25.060196.001311. [DOI] [PubMed] [Google Scholar]
  17. Koeppe R. E., 2nd, Killian J. A., Greathouse D. V. Orientations of the tryptophan 9 and 11 side chains of the gramicidin channel based on deuterium nuclear magnetic resonance spectroscopy. Biophys J. 1994 Jan;66(1):14–24. doi: 10.1016/S0006-3495(94)80748-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Langs D. A. Three-dimensional structure at 0.86 A of the uncomplexed form of the transmembrane ion channel peptide gramicidin A. Science. 1988 Jul 8;241(4862):188–191. doi: 10.1126/science.2455345. [DOI] [PubMed] [Google Scholar]
  19. Lee K. C., Cross T. A. Side-chain structure and dynamics at the lipid-protein interface: Val1 of the gramicidin A channel. Biophys J. 1994 May;66(5):1380–1387. doi: 10.1016/S0006-3495(94)80928-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lee K. C., Huo S., Cross T. A. Lipid-peptide interface: valine conformation and dynamics in the gramicidin channel. Biochemistry. 1995 Jan 24;34(3):857–867. doi: 10.1021/bi00003a020. [DOI] [PubMed] [Google Scholar]
  21. Lundbaek J. A., Maer A. M., Andersen O. S. Lipid bilayer electrostatic energy, curvature stress, and assembly of gramicidin channels. Biochemistry. 1997 May 13;36(19):5695–5701. doi: 10.1021/bi9619841. [DOI] [PubMed] [Google Scholar]
  22. MacDonald R. C., Simon S. A. Lipid monolayer states and their relationships to bilayers. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4089–4093. doi: 10.1073/pnas.84.12.4089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mukherjee S., Chattopadhyay A. Motionally restricted tryptophan environments at the peptide-lipid interface of gramicidin channels. Biochemistry. 1994 May 3;33(17):5089–5097. doi: 10.1021/bi00183a012. [DOI] [PubMed] [Google Scholar]
  24. Reithmeier R. A. Characterization and modeling of membrane proteins using sequence analysis. Curr Opin Struct Biol. 1995 Aug;5(4):491–500. doi: 10.1016/0959-440x(95)80034-4. [DOI] [PubMed] [Google Scholar]
  25. Rice D., Oldfield E. Deuterium nuclear magnetic resonance studies of the interaction between dimyristoylphosphatidylcholine and gramicidin A'. Biochemistry. 1979 Jul 24;18(15):3272–3279. doi: 10.1021/bi00582a012. [DOI] [PubMed] [Google Scholar]
  26. Ring A. Gramicidin channel-induced lipid membrane deformation energy: influence of chain length and boundary conditions. Biochim Biophys Acta. 1996 Jan 31;1278(2):147–159. doi: 10.1016/0005-2736(95)00220-0. [DOI] [PubMed] [Google Scholar]
  27. Roux B., Karplus M. Molecular dynamics simulations of the gramicidin channel. Annu Rev Biophys Biomol Struct. 1994;23:731–761. doi: 10.1146/annurev.bb.23.060194.003503. [DOI] [PubMed] [Google Scholar]
  28. Tanford C. Hydrostatic pressure in small phospholipid vesicles. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3318–3319. doi: 10.1073/pnas.76.7.3318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Urry D. W. The gramicidin A transmembrane channel: a proposed pi(L,D) helix. Proc Natl Acad Sci U S A. 1971 Mar;68(3):672–676. doi: 10.1073/pnas.68.3.672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wallace B. A., Ravikumar K. The gramicidin pore: crystal structure of a cesium complex. Science. 1988 Jul 8;241(4862):182–187. doi: 10.1126/science.2455344. [DOI] [PubMed] [Google Scholar]
  31. White S. H. Small phospholipid vesicles: internal pressure, surface tension, and surface free energy. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4048–4050. doi: 10.1073/pnas.77.7.4048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wimley W. C., White S. H. Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat Struct Biol. 1996 Oct;3(10):842–848. doi: 10.1038/nsb1096-842. [DOI] [PubMed] [Google Scholar]
  33. Woolf T. B., Roux B. Structure, energetics, and dynamics of lipid-protein interactions: A molecular dynamics study of the gramicidin A channel in a DMPC bilayer. Proteins. 1996 Jan;24(1):92–114. doi: 10.1002/(SICI)1097-0134(199601)24:1<92::AID-PROT7>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  34. Xing J., Scott H. L. Monte Carlo studies of a model for lipid-gramicidin A bilayers. Biochim Biophys Acta. 1992 Apr 29;1106(1):227–232. doi: 10.1016/0005-2736(92)90243-f. [DOI] [PubMed] [Google Scholar]

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