Effect of ionic aqueous environments on the structure and dynamics of the Aβ(21-30) fragment: a molecular-dynamics...

The amyloid β-protein (Aβ) has been implicated in the pathogenesis of Alzheimer's disease. The role of the structure and dynamics of the central Aβ21-30 decapeptide region of the full-length Aβ is considered crucial in the aggregation pathway of Aβ. Here we report results of isobaric-isothermal (NPT) all-atom explicit water molecular dynamics simulations of the monomeric form of the wild-type Aβ21-30 fragment in aqueous salt environments formed by neurobiologically important group IA (NaCl, KCl) and group IIA (CaCl2, MgCl2) salts. Our simulations reveal the existence of salt-specific changes to secondary structure propensities, lifetimes, hydrogen bonding, salt-bridge formation, and decapeptide-ion contacts of this decapeptide. These results suggest that aqueous environments with the CaCl2 salt, and to a much lesser extent the MgCl2 salt, have profound effects by increasing random coil structure propensities and lifetimes and diminishing intrapeptide hydrogen bonding. These effects are rationalized in terms of direct cation-decapeptide contacts and changes to the hydration-shell water molecules. On the other side of the spectrum, environments with the NaCl and KCl salts have little influence on the decapeptide's secondary structure despite increasing hydrogen bonding, salt-bridge formation, and lifetime of turn structures. The observed enhancement of open structures by group IIA may be of importance in the folding and aggregation pathway of the full-length Aβ.