Nucleation process of a fibril precursor in the C-terminal segment of amyloid-beta

Fahimeh Baftizadeh, Fabio Pietrucci, Xevi Biarnés, Alessandro Laio

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50 Citations (Scopus)


By extended atomistic simulations in explicit solvent and bias-exchange metadynamics, we study the aggregation process of 18 chains of the C-terminal segment of amyloid-β, an intrinsically disordered protein involved in Alzheimer's disease and prone to form fibrils. Starting from a disordered aggregate, we are able to observe the formation of an ordered nucleus rich in beta sheets. The rate limiting step in the nucleation pathway involves crossing a barrier of approximately 40 kcal/mol and is associated with the formation of a very specific interdigitation of the side chains belonging to different sheets. This structural pattern is different from the one observed experimentally in a microcrystal of the same system, indicating that the structure of a "nascent" fibril may differ from the one of an "extended" fibril.

Original languageEnglish
Article number168103
Number of pages5
JournalPhysical Review Letters
Issue number16
Publication statusPublished - 17 Apr 2013


  • Molecular-dynamics simulations
  • Monte-carlo simulations
  • Alzheimers-disease
  • Peptide
  • Aggregation
  • Oligomers
  • State
  • Conformations
  • A-beta(16-22)
  • Mechanism


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