A bottom-up approach to the ion recognition mechanism of K channels from laser spectroscopy of hydrated partial peptide-alkali metal ion complexes

K + channels allow selective permeation of K + , but not physiologically abundant Na + , at almost diffusion limit rates. The conduction mechanism of K + channels is still controversial, with experimental and computation studies supporting two distinct conduction mechanisms: either with or without water inside the channel. Here, we employ a bottom-up approach on hydrated alkali metal complexes of a model peptide of K + channels, Ac-Tyr-NHMe, to characterize metal-peptide, metal-water, and water-peptide interactions that govern the selectivity of K + channels at a molecular level. Both the extension to the series of alkali metal ions and to temperature-dependent studies (approaching physiological values) have revealed the clear difference between permeable and non-permeable ions in the spectral features of the ion complexes. Furthermore, the impact of hydration is discussed in relation to the K + channels by comparisons of the non-hydrated and hydrated complexes. Hydration impacts alkali metal ion-peptide conformations for the largest and smallest ions, but has only a small effect on K + , the most permeable ion in K + channels.