A predictive MD-Nernst-Planck model for transport in alpha-hemolysin: Modeling anisotropic ion currents

A multiscale simulation approach, combining molecular dynamics (MD) and Poisson-Nernst-Planck (PNP) models is used to predict voltage-driven KCl current flow through an α-hemolysin channel. I-V characteristics are calculated for salt concentrations ranging from 50 mM to 3 M. The results show that the fixed charge distribution in the pore walls acts like a macrodipole and introduces a diffusion current component that is responsible for the well-established anisotropic current response. We show that for KCl concentrations in the biological range (50-100 mM), where the Debye length is calculated to be ∼4 Å, ion currents are dominated by the diffusion component. Conversely, for KCl concentrations in excess of 1 M ion currents approach an isotropic, surface chemistry invariant limit. We calculate 0.1 M I-V characteristics for a range of protein dielectric constant εp and show that εp ∼ 21, is appropriate to account for protein relaxation and self-energy polarization contributions, and is necessary to avoid overestimating the ion current. We show that a generalize form of the Goldman-Hodgkin-Katz (GHK) current equation, using the calculated channel voltage profile captures the current rectifying nature of the α-hemolysin channel.