Non-Equilibrium Molecular Dynamics Study of Ion Permeation through the Biological Ion Channel alpha-Hemolysin

Ion permeation properties and current-voltage (I-V) characteristics of the ion channel alpha-hemolysin (a-HL) have been calculated using non-equilibrium molecular dynamics (NEMD). In the simulation setup for our calculations, the channel was embedded in a layer of dummy atoms, which serve as an artificial membrane, and the channel structure was frozen, or held motionless throughout the simulation. This setup served to significantly reduce computational load while testing to see if realistic permeant and I-V properties for the system were maintained, by comparison to both experimental data as well as I-V data calculated using Poisson-Nernst-Planck (PNP) methodology. Additionally, diffusion constant values for both ion types inside the channel pore region were calculated using mean square displacement (MSD) methodology and compared to results for bulk solution, yielding a reduction in the diffusion constants inside the channel for each ion type of approximately one half their bulk values. While our preliminary results have produced qualitatively reasonable data, we concluded that the simulation would be more accurate if a portion of the channel structure, specifically those residues found at the protein-solvent interface, is allowed to move freely for future calculations