The Solvation and Permeation of Ions

Ions are central to cell signalling and energetics. The ion concentration gradients across cellular membranes are controlled by a series of transporters and channels that can select for ions based on valency and size. One example is the KcsA K⁺ channel, which allows the passage of K⁺ over Na⁺ by many orders of magnitude. This selectivity is enforced by a narrow filter comprised of a series of ion binding sites. The selectivity of these sites was quantified by Ba²⁺ blockade experiments that found that K⁺ in the external solution impedes the exit of Ba²⁺ from the channel even at µm concentrations, while Na⁺ has no effect. We used molecular dynamics simulations to interpret these experiments in the context of the high resolution crystal structure of this channel. We see high barriers corresponding to the translocation of Ba²⁺ ions between sites in the filter. These barriers are increased when an alkali ion in solution binds to an external site, consistent with the reported “lock-in” effect. [1]

While these simulations can provide insight into the mechanisms of these channels, divalent ions like Ba²⁺ are challenging, as they can strongly polarize their environment, an effect that is neglected in current models. We used hybrid QM/MM models to examine the solvation of Mg²⁺ and Zn²⁺ ions - two divalent ions of the same size and charge but with totally different roles in the cell. We find that the greater Lewis acidity of Zn²⁺ determines allows greater metal-to-ligand charge transfer, increasing its ability to bind to Lewis donor ligands. [2]

[1] Rowley, C.N., Roux, B. A Computational Study of Barium Blockades in the KcsA Potassium Channel Based on Multi-ion Potential of Mean Force Calculations and Free Energy Perturbation. J. Gen. Physiol. 142 (4), 451–463, 2013

[2] Riahi, S., Roux, B., Rowley, C.N. QM/MM Molecular Dynamics Simulations of the Hydration of Mg(II) and Zn(II) Ions. Can. J. Chem. 91 (7), 552–558, 2013