Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1999 Nov;77(5):2502–2516. doi: 10.1016/S0006-3495(99)77086-4

Molecular dynamics study of the KcsA potassium channel

TW Allen 1, S Kuyucak 1, SH Chung 1
PMCID: PMC1300526  PMID: 10545352

Abstract

The structural, dynamical, and thermodynamic properties of a model potassium channel are studied using molecular dynamics simulations. We use the recently unveiled protein structure for the KcsA potassium channel from Streptomyces lividans. Total and free energy profiles of potassium and sodium ions reveal a considerable preference for the larger potassium ions. The selectivity of the channel arises from its ability to completely solvate the potassium ions, but not the smaller sodium ions. Self-diffusion of water within the narrow selectivity filter is found to be reduced by an order of magnitude from bulk levels, whereas the wider hydrophobic section of the pore maintains near-bulk self-diffusion. Simulations examining multiple ion configurations suggest a two-ion channel. Ion diffusion is found to be reduced to approximately (1)/(3) of bulk diffusion within the selectivity filter. The reduced ion mobility does not hinder the passage of ions, as permeation appears to be driven by Coulomb repulsion within this multiple ion channel.

Full Text

The Full Text of this article is available as a PDF (265.0 KB).

Selected References

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

  1. Bezanilla F., Armstrong C. M. Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons. J Gen Physiol. 1972 Nov;60(5):588–608. doi: 10.1085/jgp.60.5.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Breed J., Sankararamakrishnan R., Kerr I. D., Sansom M. S. Molecular dynamics simulations of water within models of ion channels. Biophys J. 1996 Apr;70(4):1643–1661. doi: 10.1016/S0006-3495(96)79727-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Daggett V., Levitt M. Realistic simulations of native-protein dynamics in solution and beyond. Annu Rev Biophys Biomol Struct. 1993;22:353–380. doi: 10.1146/annurev.bb.22.060193.002033. [DOI] [PubMed] [Google Scholar]
  4. Doyle D. A., Morais Cabral J., Pfuetzner R. A., Kuo A., Gulbis J. M., Cohen S. L., Chait B. T., MacKinnon R. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science. 1998 Apr 3;280(5360):69–77. doi: 10.1126/science.280.5360.69. [DOI] [PubMed] [Google Scholar]
  5. Ferrenberg AM, Swendsen RH. Optimized Monte Carlo data analysis. Phys Rev Lett. 1989 Sep 18;63(12):1195–1198. doi: 10.1103/PhysRevLett.63.1195. [DOI] [PubMed] [Google Scholar]
  6. Hahn K, Kärger J, Kukla V., V Single-file diffusion observation. Phys Rev Lett. 1996 Apr 8;76(15):2762–2765. doi: 10.1103/PhysRevLett.76.2762. [DOI] [PubMed] [Google Scholar]
  7. Hol W. G., van Duijnen P. T., Berendsen H. J. The alpha-helix dipole and the properties of proteins. Nature. 1978 Jun 8;273(5662):443–446. doi: 10.1038/273443a0. [DOI] [PubMed] [Google Scholar]
  8. Kiss L., LoTurco J., Korn S. J. Contribution of the selectivity filter to inactivation in potassium channels. Biophys J. 1999 Jan;76(1 Pt 1):253–263. doi: 10.1016/S0006-3495(99)77194-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mezei M., Beveridge D. L. Free energy simulations. Ann N Y Acad Sci. 1986;482:1–23. doi: 10.1111/j.1749-6632.1986.tb20933.x. [DOI] [PubMed] [Google Scholar]
  10. Roux B., Karplus M. Ion transport in a model gramicidin channel. Structure and thermodynamics. Biophys J. 1991 May;59(5):961–981. doi: 10.1016/S0006-3495(91)82311-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Sankararamakrishnan R., Adcock C., Sansom M. S. The pore domain of the nicotinic acetylcholine receptor: molecular modeling, pore dimensions, and electrostatics. Biophys J. 1996 Oct;71(4):1659–1671. doi: 10.1016/S0006-3495(96)79370-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sansom M. S., Kerr I. D., Breed J., Sankararamakrishnan R. Water in channel-like cavities: structure and dynamics. Biophys J. 1996 Feb;70(2):693–702. doi: 10.1016/S0006-3495(96)79609-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schrempf H., Schmidt O., Kümmerlen R., Hinnah S., Müller D., Betzler M., Steinkamp T., Wagner R. A prokaryotic potassium ion channel with two predicted transmembrane segments from Streptomyces lividans. EMBO J. 1995 Nov 1;14(21):5170–5178. doi: 10.1002/j.1460-2075.1995.tb00201.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Singh C., Sankararamakrishnan R., Subramaniam S., Jakobsson E. Solvation, water permeation, and ionic selectivity of a putative model for the pore region of the voltage-gated sodium channel. Biophys J. 1996 Nov;71(5):2276–2288. doi: 10.1016/S0006-3495(96)79438-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Smith G. R., Sansom M. S. Dynamic properties of Na+ ions in models of ion channels: a molecular dynamics study. Biophys J. 1998 Dec;75(6):2767–2782. doi: 10.1016/S0006-3495(98)77720-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Smith G. R., Sansom M. S. Molecular dynamics study of water and Na+ ions in models of the pore region of the nicotinic acetylcholine receptor. Biophys J. 1997 Sep;73(3):1364–1381. doi: 10.1016/S0006-3495(97)78169-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tieleman D. P., Berendsen H. J. A molecular dynamics study of the pores formed by Escherichia coli OmpF porin in a fully hydrated palmitoyloleoylphosphatidylcholine bilayer. Biophys J. 1998 Jun;74(6):2786–2801. doi: 10.1016/S0006-3495(98)77986-X. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES