Effects of Ionic Salts in Aqueous Environments on the Folding Dynamics of the 21-30 Fragment of the Amyloid Beta-Protein

Abstract

The amyloid β-protein (Aβ) has been implicated in the pathogenesis of Alzheimer's disease. Although little is known about the initial deleterious misfolding of the full-length Aβ, in vitro experiments have shown that a 21 through 30 fragment of Aβ, the Aβ(21-30), may be the folding nucleus of the full-length protein. Our previous all-atom molecular dynamics work shed light on the behavior of the Aβ(21-30) in bulk water. Here, we explore the effects on the folding dynamics of the Aβ(21-30) of dissolved ionic salts (NaCl, CaCl2, and KCl) that are common to the cellular environment. Using microsecond-long all-atom molecular dynamics we find that previously found extended beta secondary structures are suppressed by KCl, promoted by CaCl2, and slightly promoted by NaCl. Measurements of distances, radial distributions, and contacts of ions surrounding the Aβ(21-30) are also analyzed. Our results suggest that electrostatic interactions between the ions and residues play a less significant role than interactions between solvent and residues due to structure ordering of solvent molecules by local ions.