Effect of Zn ion on the structure and electronic states of Aβ nonamer: molecular dynamics and ab initio molecular orbital calculations

Aggregates of amyloid-beta proteins (A beta) have been recognised to be intimately related to pathogenesis of Alzheimer's disease (AD). Indeed, A beta aggregates of various sizes from dimers to fibrils were found in the brains of AD patients, and these aggregates can be self-organised. Since abnormal accumulation of metal ions such as Zn, Cu and Fe was also observed in the brains, the association between A beta aggregations and these metal ions has been studied widely. In the present study, to elucidate the influence of Zn ions on the stability of A beta aggregates, we performed molecular dynamics (MD) simulations and ab initio fragment molecular orbital (FMO) calculations on the A beta nonamers with and without Zn ions and investigated the change in its structure and electronic states induced by Zn ions at atomic and electronic levels. The MD simulations revealed that A beta nonamer cannot keep its symmetry structure, whereas A beta nonamer with Zn ions keeps the structure. The FMO results indicated that electrostatic interactions among the charged amino-acid residues of A beta nonamer are significantly changed by the influence of Zn ions to stabilise A beta nonamer. These results provide useful information for proposing novel compounds, which binds specifically to A beta and inhibits the A beta aggregation.