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Anders Irbäck. Photo.

Anders Irbäck

Professor

Anders Irbäck. Photo.

Aggregate geometry in amyloid fibril nucleation.

Author

  • Anders Irbäck
  • Sigurdur Jonsson
  • Niels Linnemann
  • Björn Linse
  • Stefan Wallin

Summary, in English

We present and study a minimal structure-based model for the self-assembly of peptides into ordered β-sheet-rich fibrils. The peptides are represented by unit-length sticks on a cubic lattice and interact by hydrogen bonding and hydrophobicity forces. Using Monte Carlo simulations with >10^{5} peptides, we show that fibril formation occurs with sigmoidal kinetics in the model. To determine the mechanism of fibril nucleation, we compute the joint distribution in length and width of the aggregates at equilibrium, using an efficient cluster move and flat-histogram techniques. This analysis, based on simulations with 256 peptides in which aggregates form and dissolve reversibly, shows that the main free-energy barriers that a nascent fibril has to overcome are associated with changes in width.

Department/s

  • Computational Biology and Biological Physics
  • MultiPark: Multidisciplinary research focused on Parkinson´s disease

Publishing year

2013

Language

English

Publication/Series

Physical Review Letters

Volume

110

Issue

5

Document type

Journal article

Publisher

American Physical Society

Topic

  • Other Physics Topics
  • Biophysics

Status

Published

ISBN/ISSN/Other

  • ISSN: 1079-7114