Referenced in: none

Automatically associated channels: Kv4.1 , Slo1

Title: Ionic permeation free energy in gramicidin: a semimicroscopic perspective.

Authors: Vladimir L Dorman, Peter C Jordan

Journal, date & volume: Biophys. J., 2004 Jun , 86, 3529-41

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15189852

Abstract
Ion permeation through the gramicidin channel is studied using a model that circumvents two major difficulties inherent to standard simulational methods. It exploits the timescale separation between electronic and structural contributions to dielectric stabilization, accounting for the influence of electronic polarization by embedding the channel in a dielectric milieu that describes this polarization in a mean sense. The explicit mobile moieties are the ion, multipolar waters, and the carbonyls and amides of the peptide backbone. The model treats the influence of aromatic residues and the membrane dipole potential. A new electrical geometry is introduced that treats long-range electrostatics exactly and avoids problems related to periodic boundary conditions. It permits the translocating ion to make a seamless transition from nearby electrolyte to the channel interior. Other degrees of freedom (more distant bulk electrolyte and nonpolar lipid) are treated as dielectric continua. Reasonable permeation free energy profiles are obtained for potassium, rubidium, and cesium; binding wells are shallow and the central barrier is small. Estimated cationic single-channel conductances are smaller than experiment, but only by factors between 2 (rubidium) and 50 (potassium). When applied to chloride the internal barrier is large, with a corresponding miniscule single-channel conductance. The estimated relative single-channel conductances of gramicidin A, B, and C agree well with experiment.