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

ABSTRACT

Aggregates of amyloid-beta proteins (Aβ) have been recognised to be intimately related to pathogenesis of Alzheimer’s disease (AD). Indeed, Aβ 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 Aβ aggregations and these metal ions has been studied widely. In the present study, to elucidate the influence of Zn ions on the stability of Aβ aggregates, we performed molecular dynamics (MD) simulations and ab initio fragment molecular orbital (FMO) calculations on the Aβ 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 Aβ nonamer cannot keep its symmetry structure, whereas Aβ nonamer with Zn ions keeps the structure. The FMO results indicated that electrostatic interactions among the charged amino-acid residues of Aβ nonamer are significantly changed by the influence of Zn ions to stabilise Aβ nonamer. These results provide useful information for proposing novel compounds, which binds specifically to Aβ and inhibits the Aβ aggregation.

KEYWORDS:

• Amyloid beta
• Alzheimer’s disease
• molecular dynamics
• fragment molecular orbital
• protein-protein interaction

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the international internship programme of Japan Student Services Organization (JASSO), the student exchange programme between the institute for food biotechnology and genomics of the National Academy of Sciences of Ukraine and Toyohashi University of Technology, and the JSPS Grant-in-Aid for Challenging Exploratory Research (No. 22650061) between Toyohashi University of Technology and the three institutes of the National Academy of Sciences of Ukraine.