Conformational Free-Energy Landscapes for a Peptide in Saline Environments

AbstractThe conformations that proteins adopt in solution are a function of both their primary structure and surrounding aqueous environment. Recent experimental and computational work on small peptides, e.g., polyK, polyE, and polyR, have highlighted an interesting and unusual behavior in the presence of aqueous ions such as ClO4−, Na+, and K+. Notwithstanding the aforementioned studies, as of this writing, the nature of the driving force induced by the presence of ions and its role on the conformational stability of peptides remains only partially understood. Molecular-dynamics simulations have been performed on the heptapeptide AEAAAEA in NaCl and KCl solutions at concentrations of 0.5, 1.0, and 2.0 M. Metadynamics in conjunction with a three-dimensional model reaction coordinate was used to sample the conformational space of the peptide. All simulations were run for 2 μs. Free-energy landscapes were computed over the model reaction coordinate for the peptide in each saline assay as well as in the absence of ions. Circular dichroism spectra were also calculated from each trajectory. In the presence of Na+ and K+ ions, no increase in helicity is observed with respect to the conformation in pure water