Skip to main content
NCBI home page
Biophysical Journal logoLink to Biophysical Journal
. 1989 Jul;56(1):171–182. doi: 10.1016/S0006-3495(89)82662-1

Energetics of ion permeation through membrane channels. Solvation of Na+ by gramicidin A.

J Aqvist 1, A Warshel 1
PMCID: PMC1280462  PMID: 2473789

Abstract

Calculations of the solvation energetics for a Na+ ion inside the Gramicidin A channel and in water are presented. The protein dipoles Langevin dipoles (PDLD) method is used to obtain an electrostatic free energy profile for ion permeation through the channel. To gauge the quality of the PDLD results the solvation free energy of a Na+ ion in water and in the center of the channel is also calculated using free energy perturbation (FEP) simulations. The effect of the polarisability of the surrounding lipid membrane is taken into account by representing the membrane by a large grid of polarisable point dipoles. The two methods give similar solvation energies in the interior of the channel and these are less than 5 kcal/mol above the solvation free energy for Na+ in water, in good agreement with experimental data on the activation barriers for ion permeation. It appears that the problems associated with previous calculations of energy profiles in membrane channels can be overcome by a consistent treatment of all the relevant electrostatic contributions. In particular, we find that the induced dipoles of the membrane and the protein contributes with approximately 10 kcal/mol to the solvation energy inside the channel and can therefore not be discarded in a realistic description of ion solvation in the Gramicidin channel.

Full text

PDF
171

Images in this article

174FIGURE 1
on p.174
176FIGURE 2
on p.176

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. Andersen O. S. Ion movement through gramicidin A channels. Single-channel measurements at very high potentials. Biophys J. 1983 Feb;41(2):119–133. doi: 10.1016/S0006-3495(83)84414-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Apell H. J., Bamberg E., Läuger P. Effects of surface charge on the conductance of the gramicidin channel. Biochim Biophys Acta. 1979 Apr 19;552(3):369–378. doi: 10.1016/0005-2736(79)90181-0. [DOI] [PubMed] [Google Scholar]
  4. Bamberg E., Apell H. J., Alpes H. Structure of the gramicidin A channel: discrimination between the piL,D and the beta helix by electrical measurements with lipid bilayer membranes. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2402–2406. doi: 10.1073/pnas.74.6.2402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Bash P. A., Singh U. C., Langridge R., Kollman P. A. Free energy calculations by computer simulation. Science. 1987 May 1;236(4801):564–568. doi: 10.1126/science.3576184. [DOI] [PubMed] [Google Scholar]
  7. Brisson A., Unwin P. N. Quaternary structure of the acetylcholine receptor. Nature. 1985 Jun 6;315(6019):474–477. doi: 10.1038/315474a0. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Etchebest C., Ranganathan S., Pullman A. The gramicidin A channel: comparison of the energy profiles of Na+, K+ and Cs+. Influence of the flexibility of the ethanolamine end chain on the profiles. FEBS Lett. 1984 Aug 6;173(2):301–306. doi: 10.1016/0014-5793(84)80795-4. [DOI] [PubMed] [Google Scholar]
  10. Greenblatt R. E., Blatt Y., Montal M. The structure of the voltage-sensitive sodium channel. Inferences derived from computer-aided analysis of the Electrophorus electricus channel primary structure. FEBS Lett. 1985 Dec 2;193(2):125–134. doi: 10.1016/0014-5793(85)80136-8. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Jordan P. C. Energy barriers for passage of ions through channels. Exact solution of two electrostatic problems. Biophys Chem. 1981 Jun;13(3):203–212. doi: 10.1016/0301-4622(81)80002-6. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Levitt D. G. Electrostatic calculations for an ion channel. I. Energy and potential profiles and interactions between ions. Biophys J. 1978 May;22(2):209–219. doi: 10.1016/S0006-3495(78)85485-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Myers V. B., Haydon D. A. Ion transfer across lipid membranes in the presence of gramicidin A. II. The ion selectivity. Biochim Biophys Acta. 1972 Aug 9;274(2):313–322. doi: 10.1016/0005-2736(72)90179-4. [DOI] [PubMed] [Google Scholar]
  18. Noda M., Takahashi H., Tanabe T., Toyosato M., Furutani Y., Hirose T., Asai M., Inayama S., Miyata T., Numa S. Primary structure of alpha-subunit precursor of Torpedo californica acetylcholine receptor deduced from cDNA sequence. Nature. 1982 Oct 28;299(5886):793–797. doi: 10.1038/299793a0. [DOI] [PubMed] [Google Scholar]
  19. Parsegian A. Energy of an ion crossing a low dielectric membrane: solutions to four relevant electrostatic problems. Nature. 1969 Mar 1;221(5183):844–846. doi: 10.1038/221844a0. [DOI] [PubMed] [Google Scholar]
  20. Polymeropoulos E. E., Brickmann J. Molecular dynamics of ion transport through transmembrane model channels. Annu Rev Biophys Biophys Chem. 1985;14:315–330. doi: 10.1146/annurev.bb.14.060185.001531. [DOI] [PubMed] [Google Scholar]
  21. Russell S. T., Warshel A. Calculations of electrostatic energies in proteins. The energetics of ionized groups in bovine pancreatic trypsin inhibitor. J Mol Biol. 1985 Sep 20;185(2):389–404. doi: 10.1016/0022-2836(85)90411-5. [DOI] [PubMed] [Google Scholar]
  22. Sung S. S., Jordan P. C. Why is gramicidin valence selective? A theoretical study. Biophys J. 1987 Apr;51(4):661–672. doi: 10.1016/S0006-3495(87)83391-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Warshel A., Levitt M. Theoretical studies of enzymic reactions: dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme. J Mol Biol. 1976 May 15;103(2):227–249. doi: 10.1016/0022-2836(76)90311-9. [DOI] [PubMed] [Google Scholar]
  26. Warshel A., Russell S. T. Calculations of electrostatic interactions in biological systems and in solutions. Q Rev Biophys. 1984 Aug;17(3):283–422. doi: 10.1017/s0033583500005333. [DOI] [PubMed] [Google Scholar]
  27. Warshel A., Sussman F., Hwang J. K. Evaluation of catalytic free energies in genetically modified proteins. J Mol Biol. 1988 May 5;201(1):139–159. doi: 10.1016/0022-2836(88)90445-7. [DOI] [PubMed] [Google Scholar]
  28. Warshel A., Sussman F., King G. Free energy of charges in solvated proteins: microscopic calculations using a reversible charging process. Biochemistry. 1986 Dec 30;25(26):8368–8372. doi: 10.1021/bi00374a006. [DOI] [PubMed] [Google Scholar]
  29. Young E. F., Ralston E., Blake J., Ramachandran J., Hall Z. W., Stroud R. M. Topological mapping of acetylcholine receptor: evidence for a model with five transmembrane segments and a cytoplasmic COOH-terminal peptide. Proc Natl Acad Sci U S A. 1985 Jan;82(2):626–630. doi: 10.1073/pnas.82.2.626. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES