Examining the Ensembles of Amyloid-β Monomer Variants and Their Propensities to Form Fibers Using an Energy Landscape Visualization Method

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorRice University-
Autor(es): dc.creatorSanches, Murilo N.-
Autor(es): dc.creatorKnapp, Kaitlin-
Autor(es): dc.creatorOliveira, Antonio B.-
Autor(es): dc.creatorWolynes, Peter G.-
Autor(es): dc.creatorOnuchic, José N.-
Autor(es): dc.creatorLeite, Vitor B. P.-
Data de aceite: dc.date.accessioned2025-08-21T23:33:38Z-
Data de disponibilização: dc.date.available2025-08-21T23:33:38Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-01-12-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1021/acs.jpcb.1c08525-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/230218-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/230218-
Descrição: dc.descriptionThe amyloid-β (Aβ) monomer, an intrinsically disordered peptide, is produced by the cleavage of the amyloid precursor protein, leading to Aβ-40 and Aβ-42 as major products. These two isoforms generate pathological aggregates, whose accumulation correlates with Alzheimer’s disease (AD). Experiments have shown that even though the natural abundance of Aβ-42 is smaller than that for Aβ-40, the Aβ-42 is more aggregation-prone compared to Aβ-40. Moreover, several single-point mutations are associated with early onset forms of AD. This work analyzes coarse-grained associative-memory, water-mediated, structure and energy model (AWSEM) simulations of normal Aβ-40 and Aβ-42 monomers, along with six single-point mutations associated with early onset disease. We analyzed the simulations using the energy landscape visualization method (ELViM), a reaction-coordinate-free approach suited to explore the frustrated energy landscapes of intrinsically disordered proteins. ELViM is shown to distinguish the monomer ensembles of variants that rapidly form fibers from those that do not form fibers as readily. It also delineates the amino acid contacts characterizing each ensemble. The results shed light on the potential of ELViM to probe intrinsically disordered proteins.-
Descrição: dc.descriptionDepartment of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP), São José do Rio Preto-
Descrição: dc.descriptionCenter for Theoretical Biological Physics Rice University-
Descrição: dc.descriptionDepartments of Physics and Astronomy Chemistry and Biosciences Rice University-
Descrição: dc.descriptionDepartment of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP), São José do Rio Preto-
Formato: dc.format93-99-
Idioma: dc.languageen-
Relação: dc.relationJournal of Physical Chemistry B-
???dc.source???: dc.sourceScopus-
Título: dc.titleExamining the Ensembles of Amyloid-β Monomer Variants and Their Propensities to Form Fibers Using an Energy Landscape Visualization Method-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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