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Int J Mol Sci. 2018 Jun 20;19(6). pii: E1815. doi: 10.3390/ijms19061815.

Exploring the Mechanism of Inhibition of Au Nanoparticles on the Aggregation of Amyloid-β(16-22) Peptides at the Atom Level by All-Atom Molecular Dynamics.

Song M1,2, Sun Y3, Luo Y4, Zhu Y5, Liu Y6, Li H7,8.

Author information

1
College of Mathematics and Physics, Shanghai University of Electric Power, Shanghai 200090, China. songmenghua94@163.com.
2
College of Energy and Mechanical Engineering, Shanghai University of Electric Power, Shanghai 200090, China. songmenghua94@163.com.
3
State Key Laboratory of Surface Physics, Key Laboratory of Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, 220 Handan Road, Shanghai 200433, China. wlxsunyunxiang@gmail.com.
4
State Key Laboratory of Surface Physics, Key Laboratory of Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, 220 Handan Road, Shanghai 200433, China. luoyin1986@gmail.com.
5
College of Mathematics and Physics, Shanghai University of Electric Power, Shanghai 200090, China. yyzhu027@163.com.
6
College of Mathematics and Physics, Shanghai University of Electric Power, Shanghai 200090, China. ysliu@shiep.edu.cn.
7
College of Mathematics and Physics, Shanghai University of Electric Power, Shanghai 200090, China. huiyuli@shiep.edu.cn.
8
State Key Laboratory of Surface Physics, Key Laboratory of Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, 220 Handan Road, Shanghai 200433, China. huiyuli@shiep.edu.cn.

Abstract

The abnormal self-assembly of the amyloid-β peptide into toxic β-rich aggregates can cause Alzheimer’s disease. Recently, it has been shown that small gold nanoparticles (AuNPs) inhibit Aβ aggregation and fibrillation by slowing down the nucleation process in experimental studies. However, the effects of AuNPs on Aβ oligomeric structures are still unclear. In this study, we investigate the conformation of Aβ(16-22) tetramers/octamers in the absence and presence of AuNPs using extensive all-atom molecular-dynamics simulations in explicit solvent. Our studies demonstrate that the addition of AuNPs into Aβ(16-22) solution prevents β-sheet formation, and the inhibition depends on the concentration of Aβ(16-22) peptides. A detailed analysis of the Aβ(16-22)/Aβ(16-22)/water/AuNPs interactions reveals that AuNPs inhibit the β-sheet formation resulting from the same physical forces: hydrophobic interactions. Overall, our computational study provides evidence that AuNPs are likely to inhibit Aβ(16-22) and full-length Aβ fibrillation. Thus, this work provides theoretical insights into the development of inorganic nanoparticles as drug candidates for treatment of AD.

KEYWORDS:

Au nanoparticles; all-atom molecular dynamics simulations; amyloid beta; hydrophobic interaction; inhibition mechanism; peptide aggregation

PMID:
29925792
PMCID:
PMC6032210
DOI:
10.3390/ijms19061815
[Indexed for MEDLINE]
Free PMC Article

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