title: Ion permeation in the NanC porin from Escherichia coli: free energy calculations along pathways identified by coarse-grain simulations.
abstract: Using the X-ray structure of a recently discovered bacterial protein, the N-acetylneuraminic acid-inducible channel (NanC), we investigate computationally K(+) and Cl(-) ions' permeation. We identify ion permeation pathways that are likely to be populated using coarse-grain Monte Carlo simulations. Next, we use these pathways as reaction coordinates for umbrella sampling-based free energy simulations. We find distinct tubelike pathways connecting specific binding sites for K(+) and, more pronounced, for Cl(-) ions. Both ions permeate the porin preserving almost all of their first hydration shell. The calculated free energy barriers are G(#) ≈ 4 kJ/mol and G(#) ≈ 8 kJ/mol for Cl(-) and K(+), respectively. Within the approximations associated with these values, discussed in detail in this work, we suggest that the porin is slightly selective for Cl(-) versus K(+). Our suggestion is consistent with the experimentally observed weak Cl(-) over K(+) selectivity. A rationale for the latter is suggested by a comparison with previous calculations on strongly anion selective porins.
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences , D-52425 Jülich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dreyer
authors.forename: Paul
authors.initials: P
authors.lastname: Strodel
authors.forename: Emiliano
authors.initials: E
authors.lastname: Ippoliti
authors.forename: Justin
authors.initials: J
authors.lastname: Finnerty
authors.forename: Bob
authors.initials: B
authors.lastname: Eisenberg
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D018272:Porins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D007477:Ions; C528455:NanC protein, E coli; D018272:Porins