Density Functional Studies of Rubidium Hydration to Probe the Analogy Between Rb+ and K+ in K Channels

Abstract

Many biological processes are based on the availability of dissolved ions. One example is the recent discovery of salt as a trigger of autoimmune disease. Another example, presumably related to the first, is the selective transport of dissolved ions across membranes. Rubidium (Rb+) is interesting in this respect because it serves as an analogue of potassium (K+) that conducts current through potassium (K) ion channels, even though Rb+ is slightly larger (by 0.2 A). The analogy between Rb+ and K+ is surprising because K channels have achieved renown for their ability to discriminate between ions. As an example, highly selective K channels conduct K+, but not the slightly smaller sodium (Na+) ion (size difference ∼ 0.4 A). Experimental studies of local hydration structure indicate that water hydrates these ions differently. Local hydration structure is relevant to ion conduction through K channels because permeant ions exchange water ligands for oxygens from the channel walls. To probe how the two larger ions can act as analogues despite differences in local hydration structure, we applied ab initio molecular dynamics simulations (AIMD) combined with a quantum-based free energy analysis using quasi-chemical theory (QCT). Local hydration is defined traditionally by the distance between the ion and the first minimum in the radial distribution of waters about the ion. The results reveal that a more restrictive definition of local hydration simplifies the free energy analysis and provides new insights about why Rb+ and K+ can behave analogously, and distinctly from Na+ [1].[1] Sabo, et al. Ann. Rep. Prog. Chem., Sect. C (2013) 109:266.