In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution

Autores
Masman, Marcelo Fabricio; Eisel, Ulrich L. M.; Csizmadia, Imre G.; Penke, Botond; Enriz, Ricardo Daniel; Marrink, Siewert Jan; Luiten, Paul G. M.
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Amyloid oligomers are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases including Alzheimer's disease. Using MD simulation techniques, we explored the contributions of the different structural elements of trimeric and pentameric full-length Aβ 1-42 aggregates in solution to their stability and conformational dynamics. We found that our models are stable at a temperature of 310 K, and converge toward an interdigitated side-chain packing for intermolecular contacts within the two β-sheet regions of the aggregates: β1 (residues 18-26) and β2 (residues 31-42). MD simulations reveal that the /3-strand twist is a characteristic element of Aβ-aggregates, permitting a compact, interdigitated packing of side chains from neighboring β-sheets. The β2 portion formed a tightly organized β-helix, whereas the β1 portion did not show such a firm structural organization, although it maintained its β-sheet conformation. Our simulations indicate that the hydrophobic core comprising the β2 portion of the aggregate is a crucial stabilizing element in the Aβ aggregation process. On the basis of these structure-stability findings, the β2 portion emerges as an optimal target for further antiamyloid drug design.
Fil: Masman, Marcelo Fabricio. University of Groningen; Países Bajos. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina
Fil: Eisel, Ulrich L. M.. University of Groningen; Países Bajos
Fil: Csizmadia, Imre G.. University of Toronto; Canadá. University of Szeged; Hungría
Fil: Penke, Botond. University of Szeged; Hungría
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Marrink, Siewert Jan. University of Groningen; Países Bajos
Fil: Luiten, Paul G. M.. University of Groningen; Países Bajos
Materia
Molecular dynamics
Amiloid
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/130591
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/130591
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in SolutionMasman, Marcelo FabricioEisel, Ulrich L. M.Csizmadia, Imre G.Penke, BotondEnriz, Ricardo DanielMarrink, Siewert JanLuiten, Paul G. M.Molecular dynamicsAmiloidhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Amyloid oligomers are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases including Alzheimer's disease. Using MD simulation techniques, we explored the contributions of the different structural elements of trimeric and pentameric full-length Aβ 1-42 aggregates in solution to their stability and conformational dynamics. We found that our models are stable at a temperature of 310 K, and converge toward an interdigitated side-chain packing for intermolecular contacts within the two β-sheet regions of the aggregates: β1 (residues 18-26) and β2 (residues 31-42). MD simulations reveal that the /3-strand twist is a characteristic element of Aβ-aggregates, permitting a compact, interdigitated packing of side chains from neighboring β-sheets. The β2 portion formed a tightly organized β-helix, whereas the β1 portion did not show such a firm structural organization, although it maintained its β-sheet conformation. Our simulations indicate that the hydrophobic core comprising the β2 portion of the aggregate is a crucial stabilizing element in the Aβ aggregation process. On the basis of these structure-stability findings, the β2 portion emerges as an optimal target for further antiamyloid drug design.Fil: Masman, Marcelo Fabricio. University of Groningen; Países Bajos. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; ArgentinaFil: Eisel, Ulrich L. M.. University of Groningen; Países BajosFil: Csizmadia, Imre G.. University of Toronto; Canadá. University of Szeged; HungríaFil: Penke, Botond. University of Szeged; HungríaFil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Marrink, Siewert Jan. University of Groningen; Países BajosFil: Luiten, Paul G. M.. University of Groningen; Países BajosAmerican Chemical Society2009-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/130591Masman, Marcelo Fabricio; Eisel, Ulrich L. M.; Csizmadia, Imre G.; Penke, Botond; Enriz, Ricardo Daniel; et al.; In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution; American Chemical Society; Journal of Physical Chemistry B; 113; 34; 11-2009; 11710-117191089-56471520-6106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/jp901057winfo:eu-repo/semantics/altIdentifier/doi/10.1021/jp901057winfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-26T10:29:01Zoai:ri.conicet.gov.ar:11336/130591instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-02-26 10:29:01.72CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution
title In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution
spellingShingle In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution
Masman, Marcelo Fabricio
Molecular dynamics
Amiloid
title_short In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution
title_full In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution
title_fullStr In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution
title_full_unstemmed In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution
title_sort In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution
dc.creator.none.fl_str_mv Masman, Marcelo Fabricio
Eisel, Ulrich L. M.
Csizmadia, Imre G.
Penke, Botond
Enriz, Ricardo Daniel
Marrink, Siewert Jan
Luiten, Paul G. M.
author Masman, Marcelo Fabricio
author_facet Masman, Marcelo Fabricio
Eisel, Ulrich L. M.
Csizmadia, Imre G.
Penke, Botond
Enriz, Ricardo Daniel
Marrink, Siewert Jan
Luiten, Paul G. M.
author_role author
author2 Eisel, Ulrich L. M.
Csizmadia, Imre G.
Penke, Botond
Enriz, Ricardo Daniel
Marrink, Siewert Jan
Luiten, Paul G. M.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Molecular dynamics
Amiloid
topic Molecular dynamics
Amiloid
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Amyloid oligomers are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases including Alzheimer's disease. Using MD simulation techniques, we explored the contributions of the different structural elements of trimeric and pentameric full-length Aβ 1-42 aggregates in solution to their stability and conformational dynamics. We found that our models are stable at a temperature of 310 K, and converge toward an interdigitated side-chain packing for intermolecular contacts within the two β-sheet regions of the aggregates: β1 (residues 18-26) and β2 (residues 31-42). MD simulations reveal that the /3-strand twist is a characteristic element of Aβ-aggregates, permitting a compact, interdigitated packing of side chains from neighboring β-sheets. The β2 portion formed a tightly organized β-helix, whereas the β1 portion did not show such a firm structural organization, although it maintained its β-sheet conformation. Our simulations indicate that the hydrophobic core comprising the β2 portion of the aggregate is a crucial stabilizing element in the Aβ aggregation process. On the basis of these structure-stability findings, the β2 portion emerges as an optimal target for further antiamyloid drug design.
Fil: Masman, Marcelo Fabricio. University of Groningen; Países Bajos. Universidad Nacional de San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis; Argentina
Fil: Eisel, Ulrich L. M.. University of Groningen; Países Bajos
Fil: Csizmadia, Imre G.. University of Toronto; Canadá. University of Szeged; Hungría
Fil: Penke, Botond. University of Szeged; Hungría
Fil: Enriz, Ricardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Marrink, Siewert Jan. University of Groningen; Países Bajos
Fil: Luiten, Paul G. M.. University of Groningen; Países Bajos
description Amyloid oligomers are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases including Alzheimer's disease. Using MD simulation techniques, we explored the contributions of the different structural elements of trimeric and pentameric full-length Aβ 1-42 aggregates in solution to their stability and conformational dynamics. We found that our models are stable at a temperature of 310 K, and converge toward an interdigitated side-chain packing for intermolecular contacts within the two β-sheet regions of the aggregates: β1 (residues 18-26) and β2 (residues 31-42). MD simulations reveal that the /3-strand twist is a characteristic element of Aβ-aggregates, permitting a compact, interdigitated packing of side chains from neighboring β-sheets. The β2 portion formed a tightly organized β-helix, whereas the β1 portion did not show such a firm structural organization, although it maintained its β-sheet conformation. Our simulations indicate that the hydrophobic core comprising the β2 portion of the aggregate is a crucial stabilizing element in the Aβ aggregation process. On the basis of these structure-stability findings, the β2 portion emerges as an optimal target for further antiamyloid drug design.
publishDate 2009
dc.date.none.fl_str_mv 2009-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/130591
Masman, Marcelo Fabricio; Eisel, Ulrich L. M.; Csizmadia, Imre G.; Penke, Botond; Enriz, Ricardo Daniel; et al.; In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution; American Chemical Society; Journal of Physical Chemistry B; 113; 34; 11-2009; 11710-11719
1089-5647
1520-6106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/130591
identifier_str_mv Masman, Marcelo Fabricio; Eisel, Ulrich L. M.; Csizmadia, Imre G.; Penke, Botond; Enriz, Ricardo Daniel; et al.; In Silico Study of Full-Length Amyloid 1-42 Tri- and Penta-Oligomers in Solution; American Chemical Society; Journal of Physical Chemistry B; 113; 34; 11-2009; 11710-11719
1089-5647
1520-6106
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/jp901057w
info:eu-repo/semantics/altIdentifier/doi/10.1021/jp901057w
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.665996

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