Salt Dependence of an α-Helical Peptide Folding Energy Landscapes

We used CD, UV resonance Raman spectroscopy, and molecular dynamics simulation to examine the impact of salts on the conformational equilibria and the Ramachandran Psi angle (un)folding Gibbs free energy landscape coordinate of a mainly polyalanine alpha-helical peptide, AP of sequence AAAAA-(AAARA)(3)A. NaClO4 stabilizes alpha-helical-like conformations more than does NaCl, which stabilizes more than Na2SO4 at identical ionic strengths. This alpha-helix stabilization ordering is the reverse of the Hofmeister series of anions in their ability to disorder water hydrogen bonding. Much of the NaClO4 alpha-helix stabilization results from ClO4- association with the AP terminal -NH3+ groups said Arg side chains. ClO4- stabilizes 3(10)-helix conformations but destabilizes turn conformations. The decreased Cl- and SO42- AP alpha-helix stabilization probably results from a decreased association with the Arg and terminal -NH3+ groups. Cl- is expected to have a smaller binding affinity and thus stabilizes alpha-helical conformations intermediately between NaClO4 and Na2SO4. Electrostatic screening stabilizes pi-bulge conformations.