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Aggregate geometry in amyloid fibril nucleation.

Irbäck, Anders LU ; Jonsson, Sigurdur LU ; Linnemann, Niels; Linse, Björn and Wallin, Stefan LU (2013) In Physical Review Letters 110(5).
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physical Review Letters
volume
110
issue
5
publisher
American Physical Society
external identifiers
  • wos:000314090300011
  • pmid:23414048
  • scopus:84873025905
ISSN
1079-7114
DOI
10.1103/PhysRevLett.110.058101
language
English
LU publication?
yes
id
84156d9e-1a4b-4763-a60a-cc458e54ba31 (old id 3559717)
date added to LUP
2013-03-01 15:04:59
date last changed
2019-05-31 11:33:14
@article{84156d9e-1a4b-4763-a60a-cc458e54ba31,
  abstract     = {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.},
  articleno    = {058101},
  author       = {Irbäck, Anders and Jonsson, Sigurdur and Linnemann, Niels and Linse, Björn and Wallin, Stefan},
  issn         = {1079-7114},
  language     = {eng},
  number       = {5},
  publisher    = {American Physical Society},
  series       = {Physical Review Letters},
  title        = {Aggregate geometry in amyloid fibril nucleation.},
  url          = {http://dx.doi.org/10.1103/PhysRevLett.110.058101},
  volume       = {110},
  year         = {2013},
}