AP helical stability in salt solutions

Protein dynamics depends on the environment and the inclusion of salts in the simulation of folding/unfolding becomes extremely necessary when comparing energy barriers or reaction rates with experimental results. The aim of this study is to investigate the effects of three sodium salts: $NaClO_4$,$NaCl$ and $Na_2 SO_4$ on the helical stability of AP, a mainly alanine peptide. The dependence of the peptide helical stability on the environment has been studied using Replica Exchange Molecular Dynamics (REMD) simulations, Circular Dichroism (CD) and Ultraviolet Raman Resonance Spectroscopy (UVRS) experiments. It was found that $NaClO_4$ solution strongly stabilizes the helical states and that the order in which sodium salts stabilize the peptide helical states follows a reverse Hofmeister Series ($ClO_4^- < Cl^- < SO_4^{2-})$. Another interesting result found is that $ClO_4^- $ ions are attracted to the backbone; $Cl^-$ ions are repelled while $SO_4^{2-} $ ions are attracted to the positive side chains. A thorough investigation of the ion effects on the first and second solvation water along with the Kirkwood-Buff theory for solutions allowed us to explain the physical mechanisms involved in the observed ion specific effects.