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C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ(11–42) Tetramer in Solution: Intensive MD Study

[Image: see text] Amyloid beta (Aβ) peptides are characterized as the major factors associated with neuron death in Alzheimer’s disease, which is listed as the most common form of neurodegeneration. Disordered Aβ peptides are released from proteolysis of the amyloid precursor protein. The Aβ self-as...

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Autores principales: Tung, Nguyen Thanh, Derreumaux, Philippe, Vu, Van V., Nam, Pham Cam, Ngo, Son Tung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648102/
https://www.ncbi.nlm.nih.gov/pubmed/31460204
http://dx.doi.org/10.1021/acsomega.9b00992
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author Tung, Nguyen Thanh
Derreumaux, Philippe
Vu, Van V.
Nam, Pham Cam
Ngo, Son Tung
author_facet Tung, Nguyen Thanh
Derreumaux, Philippe
Vu, Van V.
Nam, Pham Cam
Ngo, Son Tung
author_sort Tung, Nguyen Thanh
collection PubMed
description [Image: see text] Amyloid beta (Aβ) peptides are characterized as the major factors associated with neuron death in Alzheimer’s disease, which is listed as the most common form of neurodegeneration. Disordered Aβ peptides are released from proteolysis of the amyloid precursor protein. The Aβ self-assembly process roughly takes place via five steps: disordered forms → oligomers → photofibrils → mature fibrils → plaques. Although Aβ fibrils are often observed in patient brains, oligomers were recently indicated to be major neurotoxic elements. In this work, the neurotoxic compound S-shape Aβ(11–42) tetramer (S4Aβ(11–42)) was investigated over 10 μs of unbiased MD simulations. In particular, the S4Aβ(11–42) oligomer adopted a high dynamics structure, resulting in unsuccessful determination of their structures in experiments. The C-terminal was suggested as the possible nucleation of the Aβ(42) aggregation. The sequences 27–35 and 39–40 formed rich β-content, whereas other residues mostly adopted coil structures. The mean value of the β-content over the equilibrium interval is ∼42 ± 3%. Furthermore, the dissociation free energy of the S4Aβ(11–42) peptide was predicted using a biased sampling method. The obtained free energy is ΔG(US) = −58.44 kcal/mol which is roughly the same level as the corresponding value of the U-shape Aβ(17-42) peptide. We anticipate that the obtained S4Aβ(11–42) structures could be used as targets for AD inhibitor screening over the in silico study.
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spelling pubmed-66481022019-08-27 C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ(11–42) Tetramer in Solution: Intensive MD Study Tung, Nguyen Thanh Derreumaux, Philippe Vu, Van V. Nam, Pham Cam Ngo, Son Tung ACS Omega [Image: see text] Amyloid beta (Aβ) peptides are characterized as the major factors associated with neuron death in Alzheimer’s disease, which is listed as the most common form of neurodegeneration. Disordered Aβ peptides are released from proteolysis of the amyloid precursor protein. The Aβ self-assembly process roughly takes place via five steps: disordered forms → oligomers → photofibrils → mature fibrils → plaques. Although Aβ fibrils are often observed in patient brains, oligomers were recently indicated to be major neurotoxic elements. In this work, the neurotoxic compound S-shape Aβ(11–42) tetramer (S4Aβ(11–42)) was investigated over 10 μs of unbiased MD simulations. In particular, the S4Aβ(11–42) oligomer adopted a high dynamics structure, resulting in unsuccessful determination of their structures in experiments. The C-terminal was suggested as the possible nucleation of the Aβ(42) aggregation. The sequences 27–35 and 39–40 formed rich β-content, whereas other residues mostly adopted coil structures. The mean value of the β-content over the equilibrium interval is ∼42 ± 3%. Furthermore, the dissociation free energy of the S4Aβ(11–42) peptide was predicted using a biased sampling method. The obtained free energy is ΔG(US) = −58.44 kcal/mol which is roughly the same level as the corresponding value of the U-shape Aβ(17-42) peptide. We anticipate that the obtained S4Aβ(11–42) structures could be used as targets for AD inhibitor screening over the in silico study. American Chemical Society 2019-06-25 /pmc/articles/PMC6648102/ /pubmed/31460204 http://dx.doi.org/10.1021/acsomega.9b00992 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Tung, Nguyen Thanh
Derreumaux, Philippe
Vu, Van V.
Nam, Pham Cam
Ngo, Son Tung
C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ(11–42) Tetramer in Solution: Intensive MD Study
title C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ(11–42) Tetramer in Solution: Intensive MD Study
title_full C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ(11–42) Tetramer in Solution: Intensive MD Study
title_fullStr C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ(11–42) Tetramer in Solution: Intensive MD Study
title_full_unstemmed C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ(11–42) Tetramer in Solution: Intensive MD Study
title_short C-Terminal Plays as the Possible Nucleation of the Self-Aggregation of the S-Shape Aβ(11–42) Tetramer in Solution: Intensive MD Study
title_sort c-terminal plays as the possible nucleation of the self-aggregation of the s-shape aβ(11–42) tetramer in solution: intensive md study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648102/
https://www.ncbi.nlm.nih.gov/pubmed/31460204
http://dx.doi.org/10.1021/acsomega.9b00992
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