Ion permeation in the NanC porin from Escherichia coli: free energy calculations along pathways identified by coarse-grain simulations

J Phys Chem B. 2013 Oct 31;117(43):13534-42. doi: 10.1021/jp4081838. Epub 2013 Oct 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry*
  • Escherichia coli / chemistry*
  • Escherichia coli Proteins / chemistry*
  • Ions / chemistry
  • Molecular Dynamics Simulation
  • Monte Carlo Method
  • Porins / chemistry*
  • Thermodynamics

Substances

  • Bacterial Outer Membrane Proteins
  • Escherichia coli Proteins
  • Ions
  • NanC protein, E coli
  • Porins