Brady, § and Pavel Jungwirth‡*

The interactions of ions with a model peptide (a single melittin α-helix) in solutions of tetrapropylammonium sulfate or guanidinium chloride were examined by molecular dynamics simulations. The tetrapropylammonium cation shares the geometrical property of essentially flat faces with the previously examined guanidinium cation, and it was found that that this geometry leads to a strong preference for tetrapropylammonium to interact in a similar stacking type fashion with flat non-polar groups such as the indole side chain of tryptophan. In contrast to guanidinium, however, tetrapropylammonium does not exhibit strong ion pairing or clustering with sulfate counterions in the solution. Sulfate was found to interact almost exclusively and strongly with the cationic groups of the peptide, such that already in a 0.1m solution of tetrapropylammonium sulfate the 6+ charge of the peptide is effectively locally neutralized. In combination with previous simulations, neutron scattering, and biochemical experiments on the conformational stability of model peptides, the present results suggest that the Hofmeister series may be explained in higher detail by splitting ions according to the effect they have on hydrogen bonding, salt bridges, and hydrophobic interactions in the protein and how these effects are altered by the counter-ion.