Effects of ion type and concentration on the structure and aggregation of the amyloid peptide A β 16 - 22 $$ {\boldsymbol{\beta}}_{16-22} $$

Abstract

Among the various factors controlling the amyloid aggregation process, the influences of ions on the aggregation rate and the resulting structures are important aspects to consider, which can be studied by molecular simulations. There is a wide variety of protein force fields and ion models, raising the question of which model to use in such studies. To address this question, we perform molecular dynamics simulations of Aβ_16-22 , a fragment of the Alzheimer's amyloid β peptide, using different protein force fields, AMBER99SB-disp (A99-d) and CHARMM36m (C36m), and different ion parameters. The influences of NaCl and CaCl₂ at various concentrations are studied and compared with the systems without the addition of ions. Our results indicate a sensitivity of the peptide-ion interactions to the different ion models. In particular, we observe a strong binding of Ca²⁺ to residue E22 with C36m and also with the Åqvist ion model used together with A99-d, which slightly affects the monomeric Aβ_16-22 structures and the aggregation rate, but significantly affects the oligomer structures formed in the aggregation simulations. For example, at high Ca²⁺ concentrations, there was a switch from an antiparallel to a parallel β-sheet. Such ionic influences are of biological relevance because local ion concentrations can change in vivo and could help explain the polymorphism of amyloid fibrils.

Keywords: Alzheimer's disease; MD simulations; amyloid aggregation; amyloid-beta; force fields; ion parameters.