Reversal of the Hofmeister Series: Specific Ion Effects
on Peptides
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Abstract
Ion-specific
effects on salting-in and salting-out of proteins,
protein denaturation, as well as enzymatic activity are typically
rationalized in terms of the Hofmeister series. Here, we demonstrate
by means of NMR spectroscopy and molecular dynamics simulations that
the traditional explanation of the Hofmeister ordering of ions in
terms of their bulk hydration properties is inadequate. Using triglycine
as a model system, we show that the Hofmeister series for anions changes
from a direct to a reversed series upon uncapping the N-terminus.
Weakly hydrated anions, such as iodide and thiocyanate, interact with
the peptide bond, while strongly hydrated anions like sulfate are
repelled from it. In contrast, reversed order in interactions of anions
is observed at the positively charged, uncapped N-terminus, and by
analogy, this should also be the case at side chains of positively
charged amino acids. These results demonstrate that the specific chemical
and physical properties of peptides and proteins play a fundamental
role in ion-specific effects. The present study thus provides a molecular
rationalization of Hofmeister ordering for the anions. It also provides
a route for tuning these interactions by titration or mutation of
basic amino acid residues on the protein surface