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 Ψ angle (un)folding Gibbs free energy landscape coordinate of a mainly polyalanine α-helical peptide, AP of sequence AAAAA-(AAARA)3A. NaClO4 stabilizes α-helical-like conformations more than does NaCl, which stabilizes more than Na 2SO4 at identical ionic strengths. This α-helix stabilization ordering is the reverse of the Hofmeister series of anions in their ability to disorder water hydrogen bonding. Much of the NaClO4 α-helix stabilization results from ClO4- association with the AP terminal-NH3+ groups and Arg side chains. ClO4- stabilizes 310-helix conformations but destabilizes turn conformations. The decreased Cl- and SO 42- AP α-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 α-helical conformations intermediately between NaClO 4 and Na2SO4. Electrostatic screening stabilizes π-bulge conformations. © 2009 American Chemical Society