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. 2002 Oct;83(4):1987–1996. doi: 10.1016/S0006-3495(02)73960-X

Molecular dynamics simulation of proton transport through the influenza A virus M2 channel.

Alexander M Smondyrev 1, Gregory A Voth 1
PMCID: PMC1302288  PMID: 12324417

Abstract

The structural and dynamical properties of a solvated proton in the influenza A virus M2 channel are studied using a molecular dynamics (MD) simulation technique. The second-generation multi-state empirical valence bond (MS-EVB2) model was used to describe the interaction between the excess proton and the channel environment. Solvation structures of the excess proton and its mobility characteristics along the channel were determined. It was found that the excess proton is capable of crossing the channel gate formed by the ring of four histidine residues even though the gate was only partially open. Although the hydronium ion itself did not cross the channel gate by traditional diffusion, the excess proton was able to transport through the ring of histidine residues by hopping between two water molecules located at the opposite sides of the gate. Our data also indicate that the proton diffusion through the channel may be correlated with the changes in channel conformations. To validate this observation, a separate simulation of the proton in a "frozen" channel has been conducted, which showed that the proton mobility becomes inhibited.

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Selected References

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  1. Brewer M. L., Schmitt U. W., Voth G. A. The formation and dynamics of proton wires in channel environments. Biophys J. 2001 Apr;80(4):1691–1702. doi: 10.1016/S0006-3495(01)76140-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Duff K. C., Ashley R. H. The transmembrane domain of influenza A M2 protein forms amantadine-sensitive proton channels in planar lipid bilayers. Virology. 1992 Sep;190(1):485–489. doi: 10.1016/0042-6822(92)91239-q. [DOI] [PubMed] [Google Scholar]
  3. Forrest L. R., Kukol A., Arkin I. T., Tieleman D. P., Sansom M. S. Exploring models of the influenza A M2 channel: MD simulations in a phospholipid bilayer. Biophys J. 2000 Jan;78(1):55–69. doi: 10.1016/s0006-3495(00)76572-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hoover WG. Canonical dynamics: Equilibrium phase-space distributions. Phys Rev A Gen Phys. 1985 Mar;31(3):1695–1697. doi: 10.1103/physreva.31.1695. [DOI] [PubMed] [Google Scholar]
  5. Kovacs F. A., Cross T. A. Transmembrane four-helix bundle of influenza A M2 protein channel: structural implications from helix tilt and orientation. Biophys J. 1997 Nov;73(5):2511–2517. doi: 10.1016/S0006-3495(97)78279-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kukol A., Adams P. D., Rice L. M., Brunger A. T., Arkin T. I. Experimentally based orientational refinement of membrane protein models: A structure for the Influenza A M2 H+ channel. J Mol Biol. 1999 Feb 26;286(3):951–962. doi: 10.1006/jmbi.1998.2512. [DOI] [PubMed] [Google Scholar]
  7. Pinto L. H., Dieckmann G. R., Gandhi C. S., Papworth C. G., Braman J., Shaughnessy M. A., Lear J. D., Lamb R. A., DeGrado W. F. A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity. Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11301–11306. doi: 10.1073/pnas.94.21.11301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Sansom M. S., Kerr I. D., Smith G. R., Son H. S. The influenza A virus M2 channel: a molecular modeling and simulation study. Virology. 1997 Jun 23;233(1):163–173. doi: 10.1006/viro.1997.8578. [DOI] [PubMed] [Google Scholar]
  9. Schumaker M. F., Pomès R., Roux B. A combined molecular dynamics and diffusion model of single proton conduction through gramicidin. Biophys J. 2000 Dec;79(6):2840–2857. doi: 10.1016/S0006-3495(00)76522-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Schumaker M. F., Pomès R., Roux B. Framework model for single proton conduction through gramicidin. Biophys J. 2001 Jan;80(1):12–30. doi: 10.1016/S0006-3495(01)75992-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Schweighofer K. J., Pohorille A. Computer simulation of ion channel gating: the M(2) channel of influenza A virus in a lipid bilayer. Biophys J. 2000 Jan;78(1):150–163. doi: 10.1016/S0006-3495(00)76581-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Smart O. S., Breed J., Smith G. R., Sansom M. S. A novel method for structure-based prediction of ion channel conductance properties. Biophys J. 1997 Mar;72(3):1109–1126. doi: 10.1016/S0006-3495(97)78760-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Smondyrev Alexander M., Voth Gregory A. Molecular dynamics simulation of proton transport near the surface of a phospholipid membrane. Biophys J. 2002 Mar;82(3):1460–1468. doi: 10.1016/S0006-3495(02)75500-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wang C., Lamb R. A., Pinto L. H. Activation of the M2 ion channel of influenza virus: a role for the transmembrane domain histidine residue. Biophys J. 1995 Oct;69(4):1363–1371. doi: 10.1016/S0006-3495(95)80003-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Wang C., Takeuchi K., Pinto L. H., Lamb R. A. Ion channel activity of influenza A virus M2 protein: characterization of the amantadine block. J Virol. 1993 Sep;67(9):5585–5594. doi: 10.1128/jvi.67.9.5585-5594.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Wang J., Kim S., Kovacs F., Cross T. A. Structure of the transmembrane region of the M2 protein H(+) channel. Protein Sci. 2001 Nov;10(11):2241–2250. doi: 10.1110/ps.17901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Zhong Q., Husslein T., Moore P. B., Newns D. M., Pattnaik P., Klein M. L. The M2 channel of influenza A virus: a molecular dynamics study. FEBS Lett. 1998 Sep 4;434(3):265–271. doi: 10.1016/s0014-5793(98)00988-0. [DOI] [PubMed] [Google Scholar]

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