Elongation dynamics of amyloid fibrils: a rugged energy landscape picture

Protein amyloid fibrils are a form of linear protein aggregates that are implicated in many neurodegenerative diseases. Here, we study the dynamics of amyloid fibril elongation by performing Langevin dynamic simulations on a coarse-grained model of peptides. Our simulation results suggest that the e...

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Bibliographic Details
Published in:Physical review. E, Statistical, nonlinear, and soft matter physics Statistical, nonlinear, and soft matter physics, 2009-10, Vol.80 (4 Pt 1), p.041906-041906, Article 041906
Main Authors: Lee, Chiu Fan, Loken, James, Jean, Létitia, Vaux, David J
Format: Article
Language:English
Subjects:
Amyloid - chemistry
Amyloid - metabolism
Hydrophobic and Hydrophilic Interactions
Kinetics
Molecular Dynamics Simulation
Protein Multimerization
Protein Structure, Quaternary
Thermodynamics
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Summary:Protein amyloid fibrils are a form of linear protein aggregates that are implicated in many neurodegenerative diseases. Here, we study the dynamics of amyloid fibril elongation by performing Langevin dynamic simulations on a coarse-grained model of peptides. Our simulation results suggest that the elongation process is dominated by a series of local minimum due to frustration in monomer-fibril interactions. This rugged energy landscape picture indicates that the amount of recycling of monomers at the fibrils' ends before being fibrilized is substantially reduced in comparison to the conventional two-step elongation model. This picture, along with other predictions discussed, can be tested with current experimental techniques.
ISSN:1539-3755
1550-2376
DOI:10.1103/PhysRevE.80.041906