Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1021/acs.jpcb.2c06178 http://hdl.handle.net/11449/246774 |
Resumo: | Understanding the details of a protein folding mechanism can be a challenging and complex task. One system with an interesting folding behavior is the α-spectrin domain, where the R15 folds three-orders of magnitude faster than its homologues R16 and R17, despite having similar structures. The molecular origins that explain these folding rate differences remain unclear, but our previous work revealed that a combined effect produced by non-native interactions could be a reasonable cause for these differences. In this study, we explore further the folding process by identifying the molecular paths, metastable states, and the collective motions that lead these unfolded proteins to their native state conformation. Our results uncovered the differences between the folding pathways for the wild-type R15 and R16 and an R16 mutant. The metastable ensembles that speed down the folding were identified using an energy landscape visualization method (ELViM). These ensembles correspond to similar experimentally reported configurations. Our observations indicate that the non-native interactions are also associated with secondary structure misdocking. This computational methodology can be used as a fast, straightforward protocol for shedding light on systems with unclear folding or conformational traps. |
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Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native InteractionsUnderstanding the details of a protein folding mechanism can be a challenging and complex task. One system with an interesting folding behavior is the α-spectrin domain, where the R15 folds three-orders of magnitude faster than its homologues R16 and R17, despite having similar structures. The molecular origins that explain these folding rate differences remain unclear, but our previous work revealed that a combined effect produced by non-native interactions could be a reasonable cause for these differences. In this study, we explore further the folding process by identifying the molecular paths, metastable states, and the collective motions that lead these unfolded proteins to their native state conformation. Our results uncovered the differences between the folding pathways for the wild-type R15 and R16 and an R16 mutant. The metastable ensembles that speed down the folding were identified using an energy landscape visualization method (ELViM). These ensembles correspond to similar experimentally reported configurations. Our observations indicate that the non-native interactions are also associated with secondary structure misdocking. This computational methodology can be used as a fast, straightforward protocol for shedding light on systems with unclear folding or conformational traps.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Physics São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Sciences, São PauloDepartment of Pharmaceutical Sciences University of Maryland School of PharmacyCenter for Theoretical Biological Physics Rice UniversityDepartment of Physics São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Sciences, São PauloUniversidade Estadual Paulista (UNESP)University of Maryland School of PharmacyRice Universityda Silva, Fernando Bruno [UNESP]Martins de Oliveira, Viníciusde Oliveira Junior, Antonio BentoContessoto, Vinícius de GodoiLeite, Vitor B. P. [UNESP]2023-07-29T12:50:11Z2023-07-29T12:50:11Z2023-02-16info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1291-1300http://dx.doi.org/10.1021/acs.jpcb.2c06178Journal of Physical Chemistry B, v. 127, n. 6, p. 1291-1300, 2023.1520-52071520-6106http://hdl.handle.net/11449/24677410.1021/acs.jpcb.2c061782-s2.0-85147526050Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Physical Chemistry Binfo:eu-repo/semantics/openAccess2023-07-29T12:50:11Zoai:repositorio.unesp.br:11449/246774Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T23:22:35.989547Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions |
title |
Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions |
spellingShingle |
Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions da Silva, Fernando Bruno [UNESP] |
title_short |
Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions |
title_full |
Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions |
title_fullStr |
Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions |
title_full_unstemmed |
Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions |
title_sort |
Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions |
author |
da Silva, Fernando Bruno [UNESP] |
author_facet |
da Silva, Fernando Bruno [UNESP] Martins de Oliveira, Vinícius de Oliveira Junior, Antonio Bento Contessoto, Vinícius de Godoi Leite, Vitor B. P. [UNESP] |
author_role |
author |
author2 |
Martins de Oliveira, Vinícius de Oliveira Junior, Antonio Bento Contessoto, Vinícius de Godoi Leite, Vitor B. P. [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (UNESP) University of Maryland School of Pharmacy Rice University |
dc.contributor.author.fl_str_mv |
da Silva, Fernando Bruno [UNESP] Martins de Oliveira, Vinícius de Oliveira Junior, Antonio Bento Contessoto, Vinícius de Godoi Leite, Vitor B. P. [UNESP] |
description |
Understanding the details of a protein folding mechanism can be a challenging and complex task. One system with an interesting folding behavior is the α-spectrin domain, where the R15 folds three-orders of magnitude faster than its homologues R16 and R17, despite having similar structures. The molecular origins that explain these folding rate differences remain unclear, but our previous work revealed that a combined effect produced by non-native interactions could be a reasonable cause for these differences. In this study, we explore further the folding process by identifying the molecular paths, metastable states, and the collective motions that lead these unfolded proteins to their native state conformation. Our results uncovered the differences between the folding pathways for the wild-type R15 and R16 and an R16 mutant. The metastable ensembles that speed down the folding were identified using an energy landscape visualization method (ELViM). These ensembles correspond to similar experimentally reported configurations. Our observations indicate that the non-native interactions are also associated with secondary structure misdocking. This computational methodology can be used as a fast, straightforward protocol for shedding light on systems with unclear folding or conformational traps. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29T12:50:11Z 2023-07-29T12:50:11Z 2023-02-16 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1021/acs.jpcb.2c06178 Journal of Physical Chemistry B, v. 127, n. 6, p. 1291-1300, 2023. 1520-5207 1520-6106 http://hdl.handle.net/11449/246774 10.1021/acs.jpcb.2c06178 2-s2.0-85147526050 |
url |
http://dx.doi.org/10.1021/acs.jpcb.2c06178 http://hdl.handle.net/11449/246774 |
identifier_str_mv |
Journal of Physical Chemistry B, v. 127, n. 6, p. 1291-1300, 2023. 1520-5207 1520-6106 10.1021/acs.jpcb.2c06178 2-s2.0-85147526050 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Physical Chemistry B |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1291-1300 |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129513925640192 |