title: Free energy of a potassium ion in a model of the channel formed by an amphipathic leucine-serine peptide.
abstract: We use molecular dynamics simulations to investigate the position-dependent free energy of a potassium ion in a model of an ion channel formed by the synthetic amphipathic leucine-serine peptide, LS3. The channel model is a parallel bundle of six LS3 helices around which are packed 146 methane-like spheres in order to mimic a membrane. At either end of and within the channel are 1051 water molecules, plus four ions (two potassium and two chloride). The free energy of a potassium ion in the channel was estimated using the weighted histogram analysis (WHAM) method. This is the first time to our knowledge that such a calculation has been carried out as a function of the position of an ion in three dimensions within a channel. The results indicate that for this channel, which is lined by hydrophilic serine sidechains, there is a relatively weak dependence of the free energy on the axial/off-axial position of the ion. There are some off-axis local minima, especially in the C-terminal half of the channel. Using the free energy results, a single channel current-voltage curve was estimated using a one-dimensional Nernst-Planck equation. Although reasonable agreement with experiment is achieved for K(+) ions flowing from the N-terminal to the C-terminal mouth, in the opposite direction the current is underestimated. This underestimation may be a consequence of under-sampling of the conformational dynamics of the channel. We suggest that our simulations may have captured, for example, a sub-conductance level (i.e. an incompletely open state) of the LS3 channel.
authors.affiliation: Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, UK.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Smith
authors.forename: Mark S P
authors.initials: MS
authors.lastname: Sansom
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry; D003198:Computer Simulation; D004553:Electric Conductivity; D004563:Electrochemistry / Q000379:methods*; D007477:Ions / Q000737:chemistry; D007930:Leucine / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011188:Potassium / Q000737:chemistry*; D015221:Potassium Channels / Q000737:chemistry*; D011487:Protein Conformation; D012680:Sensitivity and Specificity; D012694:Serine / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D007477:Ions; D015221:Potassium Channels; D013501:Surface-Active Agents; D012694:Serine; D007930:Leucine; D011188:Potassium