Skip to main content
NCBI home page
Biophysical Journal logoLink to Biophysical Journal
. 1991 May;59(5):961–981. doi: 10.1016/S0006-3495(91)82311-6

Ion transport in a model gramicidin channel. Structure and thermodynamics.

B Roux 1, M Karplus 1
PMCID: PMC1281331  PMID: 1714305

Abstract

The potential of mean force for Na+ and K+ ions as a function of position in the interior of a periodic poly(L,D)-alanine model for the gramicidin beta-helix is calculated with a detailed atomic model and realistic interactions. The calculated free energy barriers are 4.5 kcal/mol for Na+ and 1.0 kcal/mol for K+. A decomposition of the free energy demonstrates that the water molecules make a significant contribution to the free energy of activation. There is an increase in entropy at the transition state associated with greater fluctuations. Analysis reveals that the free energy profile of ions in the periodic channel is controlled not by the large interaction energy involving the ion but rather by the weaker water-water, water-peptide and peptide-peptide hydrogen bond interactions. The interior of the channel retains much of the solvation properties of a liquid in its interactions with the cations. Of particular importance is the flexibility of the helix, which permits it to respond to the presence of an ion in a fluidlike manner. The distortion of the helix is local (limited to a few carbonyls) because the structure is too flexible to transmit a perturbation to large distances. The plasticity of the structure (i.e., the property to deform without generating a large energy stress) appears to be an essential factor in the transport of ions, suggesting that a rigid helix model would be inappropriate.

Full text

PDF
961

Images in this article

964FIGURE 1
on p.964
971FIGURE 10
on p.971

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen O. S. Gramicidin channels. Annu Rev Physiol. 1984;46:531–548. doi: 10.1146/annurev.ph.46.030184.002531. [DOI] [PubMed] [Google Scholar]
  2. Aqvist J., Warshel A. Energetics of ion permeation through membrane channels. Solvation of Na+ by gramicidin A. Biophys J. 1989 Jul;56(1):171–182. doi: 10.1016/S0006-3495(89)82662-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arseniev A. S., Barsukov I. L., Bystrov V. F., Lomize A. L., Ovchinnikov YuA 1H-NMR study of gramicidin A transmembrane ion channel. Head-to-head right-handed, single-stranded helices. FEBS Lett. 1985 Jul 8;186(2):168–174. doi: 10.1016/0014-5793(85)80702-x. [DOI] [PubMed] [Google Scholar]
  4. Bamberg E., Läuger P. Temperature-dependent properties of gramicidin A channels. Biochim Biophys Acta. 1974 Oct 29;367(2):127–133. doi: 10.1016/0005-2736(74)90037-6. [DOI] [PubMed] [Google Scholar]
  5. Brickmann J., Fischer W. Entropy effects on the ion-diffusion rate in transmembrane protein channels. Biophys Chem. 1983 Apr;17(3):245–258. doi: 10.1016/0301-4622(83)87007-0. [DOI] [PubMed] [Google Scholar]
  6. Chiu S. W., Jakobsson E. Stochastic theory of singly occupied ion channels. II. Effects of access resistance and potential gradients extending into the bath. Biophys J. 1989 Jan;55(1):147–157. doi: 10.1016/S0006-3495(89)82786-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chiu S. W., Subramaniam S., Jakobsson E., McCammon J. A. Water and polypeptide conformations in the gramicidin channel. A molecular dynamics study. Biophys J. 1989 Aug;56(2):253–261. doi: 10.1016/S0006-3495(89)82671-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cooper K. E., Gates P. Y., Eisenberg R. S. Diffusion theory and discrete rate constants in ion permeation. J Membr Biol. 1988 Dec;106(2):95–105. doi: 10.1007/BF01871391. [DOI] [PubMed] [Google Scholar]
  9. Cooper K. E., Gates P. Y., Eisenberg R. S. Surmounting barriers in ionic channels. Q Rev Biophys. 1988 Aug;21(3):331–364. doi: 10.1017/s0033583500004480. [DOI] [PubMed] [Google Scholar]
  10. Cornell B. A., Separovic F., Baldassi A. J., Smith R. Conformation and orientation of gramicidin a in oriented phospholipid bilayers measured by solid state carbon-13 NMR. Biophys J. 1988 Jan;53(1):67–76. doi: 10.1016/S0006-3495(88)83066-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eisenman G., Horn R. Ionic selectivity revisited: the role of kinetic and equilibrium processes in ion permeation through channels. J Membr Biol. 1983;76(3):197–225. doi: 10.1007/BF01870364. [DOI] [PubMed] [Google Scholar]
  12. Finkelstein A., Andersen O. S. The gramicidin A channel: a review of its permeability characteristics with special reference to the single-file aspect of transport. J Membr Biol. 1981 Apr 30;59(3):155–171. doi: 10.1007/BF01875422. [DOI] [PubMed] [Google Scholar]
  13. Fisher R., Blumenthal T. An interaction between gramicidin and the sigma subunit of RNA polymerase. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1045–1048. doi: 10.1073/pnas.79.4.1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gao J., Kuczera K., Tidor B., Karplus M. Hidden thermodynamics of mutant proteins: a molecular dynamics analysis. Science. 1989 Jun 2;244(4908):1069–1072. doi: 10.1126/science.2727695. [DOI] [PubMed] [Google Scholar]
  15. Goodfellow J. M., Finney J. L., Barnes P. Monte Carlo computer simulation of water-amino acid interactions. Proc R Soc Lond B Biol Sci. 1982 Jan 22;214(1195):213–228. doi: 10.1098/rspb.1982.0005. [DOI] [PubMed] [Google Scholar]
  16. Hinton J. F., Fernandez J. Q., Shungu D. C., Whaley W. L., Koeppe R. E., 2nd, Millett F. S. TI-205 nuclear magnetic resonance determination of the thermodynamic parameters for the binding of monovalent cations to gramicidins A and C. Biophys J. 1988 Sep;54(3):527–533. doi: 10.1016/S0006-3495(88)82985-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hladky S. B., Haydon D. A. Ion transfer across lipid membranes in the presence of gramicidin A. I. Studies of the unit conductance channel. Biochim Biophys Acta. 1972 Aug 9;274(2):294–312. doi: 10.1016/0005-2736(72)90178-2. [DOI] [PubMed] [Google Scholar]
  18. Lee W. K., Jordan P. C. Molecular dynamics simulation of cation motion in water-filled gramicidinlike pores. Biophys J. 1984 Dec;46(6):805–819. doi: 10.1016/S0006-3495(84)84079-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Levitt D. G. Interpretation of biological ion channel flux data--reaction-rate versus continuum theory. Annu Rev Biophys Biophys Chem. 1986;15:29–57. doi: 10.1146/annurev.bb.15.060186.000333. [DOI] [PubMed] [Google Scholar]
  20. Läuger P. Ion transport through pores: a rate-theory analysis. Biochim Biophys Acta. 1973 Jul 6;311(3):423–441. doi: 10.1016/0005-2736(73)90323-4. [DOI] [PubMed] [Google Scholar]
  21. Läuger P. Microscopic calculation of ion-transport rates in membrane channels. Biophys Chem. 1982 May;15(2):89–100. doi: 10.1016/0301-4622(82)80021-5. [DOI] [PubMed] [Google Scholar]
  22. Mackay D. H., Berens P. H., Wilson K. R., Hagler A. T. Structure and dynamics of ion transport through gramicidin A. Biophys J. 1984 Aug;46(2):229–248. doi: 10.1016/S0006-3495(84)84016-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mazet J. L., Andersen O. S., Koeppe R. E., 2nd Single-channel studies on linear gramicidins with altered amino acid sequences. A comparison of phenylalanine, tryptophane, and tyrosine substitutions at positions 1 and 11. Biophys J. 1984 Jan;45(1):263–276. doi: 10.1016/S0006-3495(84)84153-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Nicholson L. K., Cross T. A. Gramicidin cation channel: an experimental determination of the right-handed helix sense and verification of beta-type hydrogen bonding. Biochemistry. 1989 Nov 28;28(24):9379–9385. doi: 10.1021/bi00450a019. [DOI] [PubMed] [Google Scholar]
  25. Pullman A. Energy profiles in the gramicidin A channel. Q Rev Biophys. 1987 Nov;20(3-4):173–200. doi: 10.1017/s0033583500004170. [DOI] [PubMed] [Google Scholar]
  26. Roux B., Karplus M. The normal modes of the gramicidin-A dimer channel. Biophys J. 1988 Mar;53(3):297–309. doi: 10.1016/S0006-3495(88)83107-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schröder H. Rate theoretical analysis of ion-selectivity in membrane channels with elastically bound ligands. Eur Biophys J. 1985;12(3):129–142. doi: 10.1007/BF00254071. [DOI] [PubMed] [Google Scholar]
  28. Skerra A., Brickmann J. Simulation of voltage-driven hydrated cation transport through narrow transmembrane channels. Biophys J. 1987 Jun;51(6):977–983. doi: 10.1016/S0006-3495(87)83425-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Skerra A., Brickmann J. Structure and dynamics of one-dimensional ionic solutions in biological transmembrane channels. Biophys J. 1987 Jun;51(6):969–976. doi: 10.1016/S0006-3495(87)83424-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Smith R., Thomas D. E., Separovic F., Atkins A. R., Cornell B. A. Determination of the structure of a membrane-incorporated ion channel. Solid-state nuclear magnetic resonance studies of gramicidin A. Biophys J. 1989 Aug;56(2):307–314. doi: 10.1016/S0006-3495(89)82677-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Urry D. W., Prasad K. U., Trapane T. L. Location of monovalent cation binding sites in the gramicidin channel. Proc Natl Acad Sci U S A. 1982 Jan;79(2):390–394. doi: 10.1073/pnas.79.2.390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Van Belle D., Couplet I., Prevost M., Wodak S. J. Calculations of electrostatic properties in proteins. Analysis of contributions from induced protein dipoles. J Mol Biol. 1987 Dec 20;198(4):721–735. doi: 10.1016/0022-2836(87)90213-0. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES