Salt Dependence of an α-Helical Peptide Folding Energy Landscapes
2009-11-17T00:00:00Z (GMT) by
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)<sub>3</sub>A. NaClO<sub>4</sub> stabilizes α-helical-like conformations more than does NaCl, which stabilizes more than Na<sub>2</sub>SO<sub>4</sub> 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 NaClO<sub>4</sub> α-helix stabilization results from ClO<sub>4</sub><sup>−</sup> association with the AP terminal −NH<sub>3</sub><sup>+</sup> groups and Arg side chains. ClO<sub>4</sub><sup>−</sup> stabilizes 3<sub>10</sub>-helix conformations but destabilizes turn conformations. The decreased Cl<sup>−</sup> and SO<sub>4</sub><sup>2−</sup> AP α-helix stabilization probably results from a decreased association with the Arg and terminal −NH<sub>3</sub><sup>+</sup> groups. Cl<sup>−</sup> is expected to have a smaller binding affinity and thus stabilizes α-helical conformations intermediately between NaClO<sub>4</sub> and Na<sub>2</sub>SO<sub>4</sub>. Electrostatic screening stabilizes π-bulge conformations.