Simulation of ion transport through an N-acetylneuraminic acid-inducible membrane channel: from understanding to engineering.

N-acetylneuraminic acid-inducible channel (NanC) is an outer membrane channel of Escherichia coli . This porin folds as a 12-stranded β-barrel leading to a tubular shape. Electrophysiological experiments have revealed an asymmetric conductance with respect to the direction of the applied voltage and a weak anion selectivity of the channel. To this end, we performed all-atom molecular dynamics (MD) simulations to decipher the ion transport properties of the NanC channel. Concentration-dependent applied-field MD simulations recover the asymmetric conductance property and the anion selectivity of the channel in agreement with experiments. Further molecular analysis revealed the role of the asymmetric charge distribution inside the channel as the basis of the asymmetry in conductance. In addition, the particular distribution of charged residues at the inner channel walls leads to a faster permeation of Cl(-) ions compared to K(+) ions resulting in the anion selectivity of NanC. These findings are well supported by position-dependent diffusion coefficients and potential of mean force profiles derived from unbiased MD simulations. Taking one step further, we were able to engineer the NanC channel in silico by mutations leading to enhanced asymmetric conductances and anion selectivities. The E186Q mutant, for example, changes NanC into a decent molecular diode with an ionic current ratio of about 3:1 for opposite bias voltages.