Exploration of the Structural Features Defining the Conduction Properties of a Synthetic Ion Channel

Abstract

The finite-difference Poisson-Boltzmann methodology was applied to a series of parallel, α-helical bundle models of the designed ion channel peptide Ac-(LSSLLSL) 3-CONH 2. This method is able to fully describe the current-voltage curves for this channel and quantitatively explains their cation selectivity and rectification. We examined a series of energy-minimized models representing different aggregation states, side-chain rotamers, and helical rotations, as well as an ensemble of structures from a molecular dynamics trajectory. Potential energies were computed for single, permeating K + and Cl − ions at a series of positions along a central pathway through the models. A variable-electric-field Nernst-Planck electrodiffusion model was used, with two adjustable parameters representing the diffusion coefficients of K + and Cl − to scale the individual ion current magnitudes. The ability of a given DelPhi potential profile to fit the experimental data depended strongly on the magnitude of the desolvation of the permeating ion. Below a pore radius of 3.8 Å, the predicted profiles showed large energy barriers, and the experimental data could be fit only with unrealistically high values for the K + and Cl − diffusion coefficients. For pore radii above 3.8 Å, the desolvation energies were 2 kT or less. The electrostatic calculations were sensitive to positioning of the Ser side chains, with the best fits associated with maximum exposure of the Ser side-chain hydroxyls to the pore. The backbone component was shown to be the major source of asymmetry in the DelPhi potential profiles. Only two of the energy-minimized structures were able to explain the experimental data, whereas an average of the dynamics structures gave excellent agreement with experimental results. Thus this method provides a promising approach to prediction of current-voltage curves from three-dimensional structures of ion channel proteins.