Formation and Growth of Oligomers: A Monte Carlo Study of an Amyloid Tau Fragment
Author Information
Author(s): Li Da-Wei, Mohanty Sandipan, Irbäck Anders, Huo Shuanghong
Primary Institution: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, Massachusetts, United States of America
Hypothesis
Small oligomers formed early in the process of amyloid fibril formation may be the major toxic species in Alzheimer's disease.
Conclusion
The study suggests that the formation of stable AcPHF6 oligomers occurs through a nucleation process, and further growth requires conformational reorganization.
Supporting Evidence
- Small oligomers rich in β-strand content were observed during the aggregation process.
- Stable oligomers were found to undergo considerable structural reorganization.
- The fraction of parallel β-sheet structure increased with aggregate size.
- Growth of stable oligomers was correlated with the alignment of strands in the β-sheets.
Takeaway
This study looks at how tiny pieces of a protein called tau stick together to form larger structures that might be harmful in diseases like Alzheimer's.
Methodology
Monte Carlo simulations were used to study the aggregation of the tau peptide AcPHF6, analyzing the formation of stable oligomers and their growth.
Limitations
The runs presented are of limited length, and some important free-energy minima may not have been sampled due to high free-energy barriers.
Digital Object Identifier (DOI)
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