Aggregate geometry in amyloid fibril nucleation.

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.

• Author: Anders Irbäck; Sigurdur Jonsson; Niels Linnemann; Björn Linse; Stefan Wallin
• Department/s: Computational Biology and Biological Physics - Has been reorganised; MultiPark: Multidisciplinary research focused on Parkinson´s disease
• Publishing year: 2013
• Language: English
• Publication/Series: Physical Review Letters
• Volume: 110
• Issue: 5
• Full text: - 460 kB; Download statistics
• Links: http://dx.doi.org/10.1103/PhysRevLett.110.058101
• Document type: Journal article
• Publisher: American Physical Society
• Topic: Other Physics Topics; Biophysics
• Status: Published
• ISBN/ISSN/Other: ISSN: 1079-7114