On the importance of atomic fluctuations, protein flexibility, and solvent in ion permeation Academic Article uri icon


MeSH Major

  • Bacterial Proteins
  • Gramicidin
  • Ion Channel Gating
  • Models, Chemical
  • Models, Molecular
  • Potassium Channels
  • Solvents


  • Proteins, including ion channels, often are described in terms of some average structure and pictured as rigid entities immersed in a featureless solvent continuum. This simplified view, which provides for a convenient representation of the protein's overall structure, incurs the risk of deemphasizing important features underlying protein function, such as thermal fluctuations in the atom positions and the discreteness of the solvent molecules. These factors become particularly important in the case of ion movement through narrow pores, where the magnitude of the thermal fluctuations may be comparable to the ion pore atom separations, such that the strength of the ion channel interactions may vary dramatically as a function of the instantaneous configuration of the ion and the surrounding protein and pore water. Descriptions of ion permeation through narrow pores, which employ static protein structures and a macroscopic continuum dielectric solvent, thus face fundamental difficulties. We illustrate this using simple model calculations based on the gramicidin A and KcsA potassium channels, which show that thermal atomic fluctuations lead to energy profiles that vary by tens of kcal/mol. Consequently, within the framework of a rigid pore model, ion-channel energetics is extremely sensitive to the choice of experimental structure and how the space-dependent dielectric constant is assigned. Given these observations, the significance of any description based on a rigid structure appears limited. Creating a conducting channel model from one single structure requires substantial and arbitrary engineering of the model parameters, making it difficult for such approaches to contribute to our understanding of ion permeation at a microscopic level.

publication date

  • December 2004



  • Academic Article



  • eng

PubMed Central ID

  • PMC2234034

Digital Object Identifier (DOI)

  • 10.1085/jgp.200409111

PubMed ID

  • 15572347

Additional Document Info

start page

  • 679

end page

  • 90


  • 124


  • 6