Strontium and barium in aqueous solution and a potassium channel binding site

Ion hydration structure and free energy establish criteria for understanding selective ion binding in potassium (K⁺) ion channels and may be significant to understanding blocking mechanisms as well. Recently, we investigated the hydration properties of Ba²⁺, the most potent blocker of K⁺ channels among the simple metal ions. Here, we use a similar method of combining ab initio molecular dynamics simulations, statistical mechanical theory, and electronic structure calculations to probe the fundamental hydration properties of Sr²⁺, which does not block bacterial K⁺ channels. The radial distribution of water around Sr²⁺ suggests a stable 8-fold geometry in the local hydration environment, similar to Ba²⁺. While the predicted hydration free energy of -331.8 kcal/mol is comparable with the experimental result of -334 kcal/mol, the value is significantly more favorable than the -305 kcal/mol hydration free energy of Ba²⁺. When placed in the innermost K⁺ channel blocking site, the solvation free energies and lowest energy structures of both Sr²⁺ and Ba²⁺ are nearly unchanged compared with their respective hydration properties. This result suggests that the block is not attributable to ion trapping due to +2 charge, and differences in blocking behavior arise due to free energies associated with the exchange of water ligands for channel ligands instead of free energies of transfer from water to the binding site.