Soft wall ion channel in continuum representation with application to modeling ion currents in α-hemolysin.

A soft repulsion (SR) model of short-range interactions between mobile ions and protein atoms is introduced in the framework of continuum representation of the protein and solvent. The Poisson-Nernst-Plank (PNP) theory of ion transport through biological channels is modified to incorporate this soft wall protein model. Two sets of SR parameters are introduced. The first is parametrized for all essential amino acid residues using all atom molecular dynamic simulations; the second is a truncated Lennard-Jones potential. We have further designed an energy-based algorithm for the determination of the ion accessible volume, which is appropriate for a particular system discretization. The effects of these models of short-range interactions were tested by computing current-voltage characteristics of the α-hemolysin channel. The introduced SR potentials significantly improve prediction of channel selectivity. In addition, we studied the effect of the choice of some space-dependent diffusion coefficient distributions on the predicted current-voltage properties. We conclude that the diffusion coefficient distributions largely affect total currents and have little effect on rectifications, selectivity, or reversal potential. The PNP-SR algorithm is implemented in a new efficient parallel Poisson, Poisson-Boltzmann, and PNP equation solver, also incorporated in a graphical molecular modeling package HARLEM.