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Influence of protein flexibility on the electrostatic energy landscape in gramicidin A

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Abstract

We describe an electrostatic model of the gramicidin A channel that allows protein atoms to move in response to the presence of a permeating ion. To do this, molecular dynamics simulations are carried out with a permeating ion at various positions within the channel. Then an ensemble of atomic coordinates taken from the simulations are used to construct energy profiles using macroscopic electrostatic calculations. The energy profiles constructed are compared to experimentally-determined conductance data by inserting them into Brownian dynamics simulations. We find that the energy landscape seen by a permeating ion changes significantly when we allow the protein atoms to move rather than using a rigid protein structure. However, the model developed cannot satisfactorily reproduce all of the experimental data. Thus, even when protein atoms are allowed to move, the dielectric model used in our electrostatic calculations breaks down when modeling the gramicidin channel.

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References

  • Allen TW, Kuyucak S, Chung SH (2000) Molecular dynamics estimates of ion diffusion in model hydrophobic and KcsA potassium channels. Biophys Chem 86:1–14

    Article  CAS  PubMed  Google Scholar 

  • Allen TW, Bastug T, Kuyucak S, Chung SH (2003a) Gramicidin A channel as a test ground for molecular dynamics force fields. Biophys J 84:2159–2168

    CAS  PubMed  Google Scholar 

  • Allen TW, Andersen OS, Roux B (2003b) Structure of gramicidin A in a lipid bilayer environment determined using molecular dynamics simulations and solid-state NMR data. J Am Chem Soc 125:9868–9877

    Article  CAS  PubMed  Google Scholar 

  • Allen TW, Andersen OS, Roux B (2004) Energetics of ion conduction through the gramicidin channel. Proc Natl Acad Sci USA 101:117–122

    Article  CAS  PubMed  Google Scholar 

  • Arseniev AS, Barsukov IL, Bystrov VF, Lomize AL, Ovchinnikov YA (1985) 1 H-NMR study of gramicidin A transmembrane ion channel: head-to-head right handed single stranded helices. FEBS Lett 186:168–174

    Article  CAS  PubMed  Google Scholar 

  • Berendsen HJC, van der Spoel D, van Drunen R (1995) GROMACS: A message-passing parallel molecular dynamics implementation. Comput Phys Commun 91:43–56

    Article  CAS  Google Scholar 

  • Bernéche S, Roux B (2003) A microscopic view of ion conduction through the K+ channel. Proc Natl Acad Sci USA 100:8644–8648

    Article  PubMed  Google Scholar 

  • Busath DD, Thulin CD, Hendershot RW, Phillips LR, Maughan P, Cole CD, Bingham NC, Morrison S, Baird LC, Hendershot RJ, Cotten M, Cross TA (1998) Noncontact dipole effects on channel permeation. I. Experiments with (5F-Indole)Trp13 gramicidin A channels. Biophys J 75:2830–2844

    CAS  PubMed  Google Scholar 

  • Chang G, Spencer RH, Lee AT, Barclay MT, Rees DC (1998) Structure of the MscL homolog from mycobacterium tuberculosis: A gated mechanosensitive ion channel. Science 282:2220–2226

    CAS  Google Scholar 

  • Chiu SW, Jakobsson E (1989) Stochastic theory of singly occupied ion channels. II. Effects of access resistance and potential gradients extending into the bath. Biophys J 55:147–157

    CAS  PubMed  Google Scholar 

  • Chung SH, Hoyles M, Allen TW, Kuyucak S (1998) Study of ionic currents across a model membrane channel using Brownian dynamics. Biophys J 75:793–809

    CAS  PubMed  Google Scholar 

  • Chung SH, Allen TW, Hoyles M, Kuyucak S (1999) Permeation of ions across the potassium channel: Brownian dynamics studies. Biophys J 77:2517–2533

    CAS  PubMed  Google Scholar 

  • Chung SH, Allen TW, Kuyucak S (2002) Conducting-state properties of the KcsA potassium channel from molecular and Brownian dynamics simulations. Biophys J 82:628–645

    CAS  PubMed  Google Scholar 

  • Cooper KE, Jakobsson E, Wolynes P (1985) The theory of ion transport through membrane channels. Prog Biophys Mol Biol 46:51–96

    Article  CAS  PubMed  Google Scholar 

  • Corry B, Kuyucak S, Chung SH (2000) Tests of continuum theories as models of ion channels: II. Poisson-Nernst-Planck theory versus Brownian dynamics. Biophys J 78:2364–2381

    CAS  PubMed  Google Scholar 

  • Corry B, Hoyles M, Allen TW, Walker M, Kuyucak S, Chung SH (2002) Reservoir boundaries in brownian dynamics simulations of ion channels. Biophys J 82: 1975–1984

    CAS  PubMed  Google Scholar 

  • Corry B, Kuyucak S, Chung SH (2003) Dielectric self-energy in Poisson-Boltzmann and Poisson-Nernst-Planck models of ion channels. Biophys J 84:3594–3606

    CAS  PubMed  Google Scholar 

  • Dorman VL, Jordan PC (2004) Ion permeation free energy in gramicidin: A semi-microscopic perspective. Biophys J 86:3529–3541

    Article  CAS  PubMed  Google Scholar 

  • Doyle DA, Cabral JM, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:69–77

    Article  CAS  PubMed  Google Scholar 

  • Dutzler R, Campbell EB, Cadene M, Cahit BT, MacKinnon R (2002) X-ray structure of a ClC chloride channel at 3.0 Å reveals the molecular basis of anion selectivity. Nature 415:287–294

    Article  CAS  PubMed  Google Scholar 

  • Edwards S, Corry B, Kuyucak S, Chung SH (2002) Continuum electrostatics fails to describe ion permeation in the gramicidin channel. Biophys J 83:1348–1360

    CAS  PubMed  Google Scholar 

  • Eisenberg RS (1999) From structure to function in open ionic channels. J Membrane Biol 171:1–24

    Article  CAS  Google Scholar 

  • Elber R, Chen DP, Rojewska D, Eisenberg R (1995) Sodium in gramicidin: and example of a permion. Biophys J 68:906–924

    CAS  PubMed  Google Scholar 

  • Feig M, Brooks CL (2004) Recent advances in the development and application of implicit solvent models in biomolecule simulations. Curr Opin Struct Biol 14:217–224

    Article  CAS  PubMed  Google Scholar 

  • van Gunsteren WF, Berendsen HJC (1982) Algorithms for Brownian dynamics. Mol Phys 45:637–647

    Google Scholar 

  • Im W, Roux B (2002) Ion permeation and selectivity of OmpF Porin: a theoretical study based on molecular dynamics, Brownian dynamics, and continuum electrodiffusion theory. J Mol Biol 322:851–869

    Article  CAS  PubMed  Google Scholar 

  • Jordan PC (1990) Ion–water and ion–polypeptide correlations in a gramicidin-like channel. Biophys J 58:1133–1156

    CAS  PubMed  Google Scholar 

  • Ketchem RR, Hu W, Cross TA (1993) High-resolution conformation of gramicidin A in a lipid bilayer by solid-state NMR. Science 261:1457–1460

    CAS  PubMed  Google Scholar 

  • Ketchem RR, Roux B, Cross TA (1997) High-resolution polypeptide structure in a lamellar phase lipid environment from solid state NMR derived orientational constraints. Structure 5:1655–1669

    Article  CAS  PubMed  Google Scholar 

  • Koeppe RE, Killian JA, Greathouse DV (1994) Orientations of the tryptophan 9 and 11 side chains of the gramicidin channel based on deuterium nuclear magnetic resonance spectroscopy. Biophys J 66:14–24

    CAS  PubMed  Google Scholar 

  • Koumanov A, Zachariae U, Englehardt H, Karshikoff A (2003) Improved 3D continuum calculations of ion flux through membrane channels. Eur Biophys J 32: 689–702

    Article  CAS  PubMed  Google Scholar 

  • Kuyucak S, Andersen OS, Chung SH (2001) Models of permeation in ion channels. Rep Prog Phys 64:1427–1472

    Article  CAS  Google Scholar 

  • Levitt DG (1986) Interpretation of biological ion channel flux data – Reaction-rate versus continuum theory. Ann Rev Biophys Biophys Chem 15:29–57

    Article  CAS  Google Scholar 

  • Li AJ, Nussinov R (1998) A set of van der Waals and Coulombic radii of protein atoms for molecular and solvent-accessible surface calculation, packing evaluation, and docking. Proteins 32:111–127

    CAS  PubMed  Google Scholar 

  • Li SC, Hoyles M, Kuyucak S, Chung SH (1998) Brownian dynamics study of ion transport in the vestibule of membrane channels. Biophys J 74:37–47

    CAS  PubMed  Google Scholar 

  • Lindahl E, Hess B, van der Spoel D (2001) GROMACS 3.0: a package for molecular simulation and trajectory analysis. J Mol Model 7:306–317

    CAS  Google Scholar 

  • MacKerell AD Jr, Bashford D, Bellot M, Dunbrack RL Jr, Evanseck JD, Field MJ, Fisher S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE III, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102:3586–3616

    Article  CAS  Google Scholar 

  • Mamonov AB, Coalson RD, Nitzan A, Kurnikova MG (2003) The role of the dielectric boundary in narrow biological channels: a novel composite approach to modeling single-channel currents. Biophys J 84:3646–3661

    CAS  PubMed  Google Scholar 

  • McGill P, Schumaker MF (1996) Boundary conditions for single-ion diffusion. Biophys J 71:1723–1742

    CAS  PubMed  Google Scholar 

  • Moy G, Corry B, Kuyucak S, Chung SH (2000) Tests of continuum theories as models of ion channels: I. Poisson-Boltzmann theory versus Brownian dynamics. Biophys J 78:2349–2363

    CAS  Google Scholar 

  • Nadler B, Hollerbach U, Eisenberg RS (2003) Dielectric boundary force and its crucial role in gramicidin. Phys Rev E 68:021905

    Article  Google Scholar 

  • Partenskii MB, Jordan PC (1992) Theoretical perspectives on ion-channel electrostatics: continuum and microscopic approaches. Q Rev Biophys 25:477–510

    CAS  PubMed  Google Scholar 

  • Roux B, Karplus M (1993) Ion transport in the gramicidin channel: free energy of the solvated right-handed dimer in a model membrane. J Am Chem Soc 115:3250–3262

    CAS  Google Scholar 

  • Roux B, Karplus M (1994) Molecular dynamics simulations of the gramicidin channel. Annu Rev Biophys Biomol Struct 23:731–761

    Article  CAS  PubMed  Google Scholar 

  • Separovic F, Barker S, Delahunty M, Smith R (1999) NMR structure of C-terminally tagged gramicidin channels. Biochim Biophys Acta 67:48–56

    Article  Google Scholar 

  • Smith GR, Sansom MSP (1999) Effective diffusion coefficients of K+ and Cl− ions in ion channel models. Biophys Chem 79:129–151

    Article  CAS  PubMed  Google Scholar 

  • Tian F, Cross TA (1999) Cation transport: an example of stuctural based selectivity. J Mol Biol 285:1993–2003

    Article  CAS  PubMed  Google Scholar 

  • Townsley LE, Tucker WA, Sham S, Hinton JF (2001) Structures of gramicidins A, B, and C Incorporated into sodium dodecyl sulfate micelles. Biochemistry 40:11676–11686

    Article  CAS  PubMed  Google Scholar 

  • Urry DW (1971) The gramicidin A transmembrane channel: a proposed π LD helix. Proc Natl Acad Sci USA 68:672–676

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank Dr. Turgut Bastug for supplying protein coordinates from his MD calculations. This work was supported by grants from the Australian Research Council, the Australian Partnership of Advanced Computing and the National Health and Medical Research Council of Australia. The calculations upon which this work is based were carried out using the Compaq AlphaServer SC of the Australian Partnership for Advanced Computing.

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  1. Chemistry, School of Biomedical and Chemical Sciences, The University of Western Australia Crawley, WA, 6009, Australia

    Ben Corry

  2. Department of Theoretical Physics, Research School of Physical Sciences, The Australian National University, Canberra, ACT, 0200, Australia

    Shin-Ho Chung

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  1. Ben Corry
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  2. Shin-Ho Chung
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Correspondence to Ben Corry.

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Corry, B., Chung, SH. Influence of protein flexibility on the electrostatic energy landscape in gramicidin A. Eur Biophys J 34, 208–216 (2005). https://doi.org/10.1007/s00249-004-0442-z

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