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Title: Amyloid oligomer structure characterization from simulations: A general method

Abstract

Amyloid oligomers and plaques are composed of multiple chemically identical proteins. Therefore, one of the first fundamental problems in the characterization of structures from simulations is the treatment of the degeneracy, i.e., the permutation of the molecules. Second, the intramolecular and intermolecular degrees of freedom of the various molecules must be taken into account. Currently, the well-known dihedral principal component analysis method only considers the intramolecular degrees of freedom, and other methods employing collective variables can only describe intermolecular degrees of freedom at the global level. With this in mind, we propose a general method that identifies all the structures accurately. The basis idea is that the intramolecular and intermolecular states are described in terms of combinations of single-molecule and double-molecule states, respectively, and the overall structures of oligomers are the product basis of the intramolecular and intermolecular states. This way, the degeneracy is automatically avoided. The method is illustrated on the conformational ensemble of the tetramer of the Alzheimer's peptide Aβ{sub 9−40}, resulting from two atomistic molecular dynamics simulations in explicit solvent, each of 200 ns, starting from two distinct structures.

Authors:
 [1];  [2]
  1. Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw (Poland)
  2. Laboratoire de Biochimie Théorique, UPR 9080, CNRS Université Denis Diderot, Sorbonne Paris Cité IBPC, 13 rue Pierre et Marie Curie, 75005 Paris (France)
Publication Date:
OSTI Identifier:
22254991
Resource Type:
Journal Article
Journal Name:
Journal of Chemical Physics
Additional Journal Information:
Journal Volume: 140; Journal Issue: 9; Other Information: (c) 2014 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0021-9606
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; DEGREES OF FREEDOM; MOLECULAR DYNAMICS METHOD; MOLECULES; PEPTIDES; SIMULATION; SOLVENTS

Citation Formats

Nguyen, Phuong H., E-mail: phuong.nguyen@ibpc.fr, Li, Mai Suan, Derreumaux, Philippe, and Institut Universitaire de France, 103 Bvd Saint-Germain, 75005 Paris. Amyloid oligomer structure characterization from simulations: A general method. United States: N. p., 2014. Web. doi:10.1063/1.4866902.
Nguyen, Phuong H., E-mail: phuong.nguyen@ibpc.fr, Li, Mai Suan, Derreumaux, Philippe, & Institut Universitaire de France, 103 Bvd Saint-Germain, 75005 Paris. Amyloid oligomer structure characterization from simulations: A general method. United States. https://doi.org/10.1063/1.4866902
Nguyen, Phuong H., E-mail: phuong.nguyen@ibpc.fr, Li, Mai Suan, Derreumaux, Philippe, and Institut Universitaire de France, 103 Bvd Saint-Germain, 75005 Paris. 2014. "Amyloid oligomer structure characterization from simulations: A general method". United States. https://doi.org/10.1063/1.4866902.
@article{osti_22254991,
title = {Amyloid oligomer structure characterization from simulations: A general method},
author = {Nguyen, Phuong H., E-mail: phuong.nguyen@ibpc.fr and Li, Mai Suan and Derreumaux, Philippe and Institut Universitaire de France, 103 Bvd Saint-Germain, 75005 Paris},
abstractNote = {Amyloid oligomers and plaques are composed of multiple chemically identical proteins. Therefore, one of the first fundamental problems in the characterization of structures from simulations is the treatment of the degeneracy, i.e., the permutation of the molecules. Second, the intramolecular and intermolecular degrees of freedom of the various molecules must be taken into account. Currently, the well-known dihedral principal component analysis method only considers the intramolecular degrees of freedom, and other methods employing collective variables can only describe intermolecular degrees of freedom at the global level. With this in mind, we propose a general method that identifies all the structures accurately. The basis idea is that the intramolecular and intermolecular states are described in terms of combinations of single-molecule and double-molecule states, respectively, and the overall structures of oligomers are the product basis of the intramolecular and intermolecular states. This way, the degeneracy is automatically avoided. The method is illustrated on the conformational ensemble of the tetramer of the Alzheimer's peptide Aβ{sub 9−40}, resulting from two atomistic molecular dynamics simulations in explicit solvent, each of 200 ns, starting from two distinct structures.},
doi = {10.1063/1.4866902},
url = {https://www.osti.gov/biblio/22254991}, journal = {Journal of Chemical Physics},
issn = {0021-9606},
number = 9,
volume = 140,
place = {United States},
year = {Fri Mar 07 00:00:00 EST 2014},
month = {Fri Mar 07 00:00:00 EST 2014}
}