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 Here, we demonstrate by means of NMR spectroscopy and, molecular dynamics simulations that the traditional explanation of the Hofmeister ordering of ions in term 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 thio cyanate, 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 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 Hefmeister 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.