Sodium Ion Binding Sites and Hydration in the Lumen of a Bacterial Ion Channel from Molecular Dynamics Simulations

Molecular dynamics (MD) calculations have been used to identify Na + binding sites in the lumen of a bacterial voltage-gated ion channel. MD trajectories have been carried out starting from the recently reported X-ray crystal structure of NavAb in a closed or inactivated conformation. The X-ray structure is stable on the time scale of the MD simulations when equilibrated in a fully hydrated lipid bilayer. Exposure to a 70 mM NaCl solution and a trajectory spanning ∼0.15 μs reveals two locations in the selectivity filter (SF) of the channel, with Na + coordinated to both water molecules and negatively charged protein residues. The nature of the Na + dynamic hydration environment has been explored, and surprisingly water seems to be able to permeate from bulk, via the SF, to the central cavity, whereas Na + ions remain near their primary SF locations, a finding that contrasts with the situation that obtains for potassium channels.