The investigation of metal-ion coordination to amyloid-beta and potential chelation materials for the treatment of Alzheimer’s disease
- Published
- Accepted
- Subject Areas
- Bioengineering, Bioinformatics, Biophysics, Computational Biology, Neuroscience
- Keywords
- Alzheimers, Biophysics, Chelation, Metals, AmyloidBeta, silicene, mos2, boron nitride
- Copyright
- © 2019 Pavuluru et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2019. The investigation of metal-ion coordination to amyloid-beta and potential chelation materials for the treatment of Alzheimer’s disease. PeerJ Preprints 7:e27942v1 https://doi.org/10.7287/peerj.preprints.27942v1
Abstract
Alzheimer's disease is a neurodegenerative disorder that results in the death of neurons and impaired cognitive function. One of the pathological hallmarks of Alzheimer's is the formation of senile plaques which originate from the aggregation of the Amyloid-β protein. Recent research has found that the overabundance of certain metal-ions in the brain may contribute to this problem, and that chelation therapy may be an effective tool to solve it. In this study, we conducted Density Functional Theory calculations to investigate the interaction of metal ions to the Amyloid-β protein, as well as the adsorption of the copper-ion by potential chelation materials. We conducted binding energy calculations and plotted the charge transfer between the metals and the substrates in order to evaluate bond strength. Binding energy calculations revealed that the binding affinities followed the order of Cu > Al > Zn, proving copper to retain the strongest affinity compared to other metal ions of biological significance. Due to copper's strong affinity, binding energies were also evaluated for its interaction with potential chelators: monolayer boron nitride, monolayer molybdenum disulfide, and monolayer silicene. Silicene produced the highest binding energies to copper, and the evidence of charge transfer between copper and the monolayers proves that there is a strong ionic bond present. Although our three monolayers did not directly present chelation potential, the absolute differences between the binding energies of the silicene binding sites and the Amyloid-β binding sites were minimal proving that further research in silicene chelators will open doors for therapy in Alzheimer's disease.
Author Comment
This is a preprint submission to PeerJ Preprints.
Supplemental Information
Amyloid-Beta Low pH and High pH metal interactions
The etotal represents the total energy of the complex