Ion permeation through a narrow channel: Using gramicidin to ascertain all-atom molecular dynamics potential of mean force methodology and biomolecular force fields Academic Article uri icon


MeSH Major

  • Cell Membrane Permeability
  • Gramicidin
  • Ion Channel Gating
  • Ion Channels
  • Membrane Potentials
  • Models, Chemical
  • Models, Molecular


  • We investigate methods for extracting the potential of mean force (PMF) governing ion permeation from molecular dynamics simulations (MD) using gramicidin A as a prototypical narrow ion channel. It is possible to obtain well-converged meaningful PMFs using all-atom MD, which predict experimental observables within order-of-magnitude agreement with experimental results. This was possible by careful attention to issues of statistical convergence of the PMF, finite size effects, and lipid hydrocarbon chain polarizability. When comparing the modern all-atom force fields of CHARMM27 and AMBER94, we found that a fairly consistent picture emerges, and that both AMBER94 and CHARMM27 predict observables that are in semiquantitative agreement with both the experimental conductance and dissociation coefficient. Even small changes in the force field, however, result in significant changes in permeation energetics. Furthermore, the full two-dimensional free-energy surface describing permeation reveals the location and magnitude of the central barrier and the location of two binding sites for K(+) ion permeation near the channel entrance--i.e., an inner site on-axis and an outer site off-axis. We conclude that the MD-PMF approach is a powerful tool for understanding and predicting the function of narrow ion channels in a manner that is consistent with the atomic and thermally fluctuating nature of proteins.

publication date

  • May 2006



  • Academic Article



  • eng

PubMed Central ID

  • PMC1440729

Digital Object Identifier (DOI)

  • 10.1529/biophysj.105.077073

PubMed ID

  • 16500984

Additional Document Info

start page

  • 3447

end page

  • 68


  • 90


  • 10