Strontium and Barium in Aqueous Solution and a Potassium Channel Binding Site

TL;DR

This study investigates the hydration properties of Sr2+ ions using simulations and calculations, revealing similarities to Ba2+ in hydration structure but differences in free energy that influence ion channel blocking behavior.

Contribution

It introduces a combined computational approach to analyze the hydration and binding properties of Sr2+ ions, expanding understanding beyond Ba2+ in potassium channels.

Findings

Sr2+ has a stable 8-fold hydration geometry similar to Ba2+.

Hydration free energy of Sr2+ is more favorable than Ba2+ (-331.8 vs -305 kcal/mol).

Water exchange free energies, not hydration free energies, likely determine blocking differences.

Abstract

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. That result suggests that differences in blocking behavior arise due to free energies associated with exchange of water ligands for channel ligands instead of free energies of transfer from water to the binding site.