IMR Press / FBL / Volume 13 / Issue 15 / DOI: 10.2741/3109

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Self-assembly of amyloid-forming peptides by molecular dynamics simulations
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1 National Key Surface Physics Laboratory and Department of Physics, Fudan University, Shanghai 200433, China
2 Laboratoire de Biochimie Theorique, UPR 9080 CNRS, Institut de Biologie, Physico-Chimique et Universite Paris 7,13 rue Pierre et Marie Curie, 75005 Paris, France
3 Departement de Physique and Regroupement Quebecois sur les Materiaux de Pointe, Universite de Montreal, C.P. 6128, succursale centre-ville, Montreal (Quebec), Canada

*Author to whom correspondence should be addressed.

Academic Editor: Buyong Ma

Front. Biosci. (Landmark Ed) 2008, 13(15), 5681–5692;
Published: 1 May 2008
(This article belongs to the Special Issue Computaional studies of protein aggregation)

Protein aggregation is associated with many neurodegenerative diseases. Understanding the aggregation mechanisms is a fundamental step in order to design rational drugs interfering with the toxic intermediates. This self-assembly process is however difficult to observe experimentally, which gives simulations an important role in resolving this problem. This study shows how we can proceed to gain knowledge about the first steps of aggregation. We first start by characterizing the free energy surface of the Abeta (16-22) dimer, a well-studied system numerically, using molecular dynamics simulations with OPEP coarse-grained force field. We then turn to the study of the NHVTLSQ peptide in 4-mers and 16-mers, extracting information on the onset of aggregation. In particular, the simulations indicate that the peptides are mostly random coil at room temperature, but can visit diverse amyloid-competent topologies, albeit with a low probability. The fact that the 16-mers constantly move from one structure to another is consistent with the long lag phase measured experimentally, but the rare critical steps leading to the rapid formation of amyloid fibrils still remain to be determined.

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