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Kinetics of amyloid aggregation: a study of the GNNQQNY prion sequence

j Nasica-Labouze and Normand Mousseau

Article (2012)

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The small amyloid-forming GNNQQNY fragment of the prion sequence has been the subject of extensive experimental and numerical studies over the last few years. Using unbiased molecular dynamics with the OPEP coarse-grained potential, we focus here on the onset of aggregation in a 20-mer system. With a total of 16.9 mus of simulations at 280 K and 300 K, we show that the GNNQQNY aggregation follows the classical nucleation theory (CNT) in that the number of monomers in the aggregate is a very reliable descriptor of aggregation. We find that the critical nucleus size in this finite-size system is between 4 and 5 monomers at 280 K and 5 and 6 at 300 K, in overall agreement with experiment. The kinetics of growth cannot be fully accounted for by the CNT, however. For example, we observe considerable rearrangements after the nucleus is formed, as the system attempts to optimize its organization. We also clearly identify two large families of structures that are selected at the onset of aggregation demonstrating the presence of well-defined polymorphism, a signature of amyloid growth, already in the 20-mer aggregate.

Uncontrolled Keywords

Amino Acid Sequence; Amyloid/*chemistry/*metabolism/ultrastructure; Biochemical Phenomena; Computational Biology; Kinetics; Molecular Dynamics Simulation; Oligopeptides/chemistry/metabolism

Subjects: 5000 Genetics > 5000 Genetics
Department: Department of Mathematics and Industrial Engineering
Funders: Natural Science and Engineering Research Council of Canada, Canada Research Chair Foundation, Fonds québécois de recherche en santé, Calcul Québec/Compute Canada for computer time
PolyPublie URL: https://publications.polymtl.ca/5053/
Journal Title: PLOS Computational Biology (vol. 8, no. 11)
Publisher: PLOS
DOI: 10.1371/journal.pcbi.1002782
Official URL: https://doi.org/10.1371/journal.pcbi.1002782
Date Deposited: 05 Apr 2022 16:03
Last Modified: 06 Apr 2024 23:31
Cite in APA 7: Nasica-Labouze, J., & Mousseau, N. (2012). Kinetics of amyloid aggregation: a study of the GNNQQNY prion sequence. PLOS Computational Biology, 8(11), e1002782. https://doi.org/10.1371/journal.pcbi.1002782


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