Ion permeation and selectivity of OmpF porin: a theoretical study based on molecular dynamics, Brownian dynamics, and continuum electrodiffusion theory.

Three different theoretical approaches are used and compared to refine our understanding of ion permeation through the channel formed by OmpF porin from Escherichia coli. Those approaches are all-atom molecular dynamics (MD) in which ions, solvent, and lipids are represented explicitly, Brownian dynamics (BD) in which ions are represented explicitly, while solvent and lipids are represented as featureless dielectrics, and Poisson-Nernst-Planck (PNP) electrodiffusion theory in which both solvent and local ion concentrations are represented as a continuum. First, the ability of the different theoretical approaches in reproducing the equilibrium average ion density distribution in OmpF porin bathed by a 1M KCl symmetric salt solution is examined. Under those conditions the PNP theory is equivalent to the non-linear Poisson-Boltzmann (PB) theory. Analysis shows that all the three approaches are able to capture the important electrostatic interactions between ions and the charge distribution of the channel that govern ion permeation and selectivity in OmpF. The K(+) and Cl(-) density distributions obtained from the three approaches are very consistent with one another, which suggests that a treatment on the basis of a rigid protein and continuum dielectric solvent is valid in the case of OmpF. Interestingly, both BD and continuum electrostatics reproduce the distinct left-handed twisted ion pathways for K(+) and Cl(-) extending over the length of the pore which were observed previously in MD. Equilibrium BD simulations in the grand canonical ensemble indicate that the channel is very attractive for cations, particularly at low salt concentration. On an average there is 1.55 K(+) inside the pore in 10mM KCl. Remarkably, there is still 0.17 K(+) on average inside the pore even at a concentration as low as 1microM KCl. Secondly, non-equilibrium ion flow through OmpF is calculated using BD and PNP and compared with experimental data. The channel conductance in 0.2M and 1M KCl calculated using BD is in excellent accord with the experimental data. The calculations reproduce the experimentally well-known conductance-concentration relation and also reveal an asymmetry in the channel conductance (a larger conductance is observed under a positive transmembrane potential). Calculations of the channel conductance for three mutants (R168A, R132A, and K16A) in 1M KCl suggest that the asymmetry in the channel conductance arises mostly from the permanent charge distribution of the channel rather than the shape of the pore itself. Lastly, the calculated reversal potential in a tenfold salt gradient (0.1:1M KCl) is 27.4(+/-1.3)mV (BD) and 22.1(+/-0.6)mV (PNP), in excellent accord with the experimental value of 24.3mV. Although most of the results from PNP are qualitatively reasonable, the calculated channel conductance is about 50% higher than that calculated from BD probably because of a lack of some dynamical ion-ion correlations.