Probing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactions

Página do item simplificado
dc.contributor.authorda Silva, Fernando Bruno [UNESP]
dc.contributor.authorMartins de Oliveira, Vinícius
dc.contributor.authorde Oliveira Junior, Antonio Bento
dc.contributor.authorContessoto, Vinícius de Godoi
dc.contributor.authorLeite, Vitor B. P. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversity of Maryland School of Pharmacy
dc.contributor.institutionRice University
dc.date.accessioned2023-07-29T12:50:11Z
dc.date.available2023-07-29T12:50:11Z
dc.date.issued2023-02-16
dc.description.abstractUnderstanding 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.en
dc.description.affiliationDepartment of Physics São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Sciences, São Paulo
dc.description.affiliationDepartment of Pharmaceutical Sciences University of Maryland School of Pharmacy
dc.description.affiliationCenter for Theoretical Biological Physics Rice University
dc.description.affiliationUnespDepartment of Physics São Paulo State University (UNESP) Institute of Biosciences Humanities and Exact Sciences, São Paulo
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent1291-1300
dc.identifierhttp://dx.doi.org/10.1021/acs.jpcb.2c06178
dc.identifier.citationJournal of Physical Chemistry B, v. 127, n. 6, p. 1291-1300, 2023.
dc.identifier.doi10.1021/acs.jpcb.2c06178
dc.identifier.issn1520-5207
dc.identifier.issn1520-6106
dc.identifier.scopus2-s2.0-85147526050
dc.identifier.urihttp://hdl.handle.net/11449/246774
dc.language.isoeng
dc.relation.ispartofJournal of Physical Chemistry B
dc.sourceScopus
dc.titleProbing the Energy Landscape of Spectrin R15 and R16 and the Effects of Non-native Interactionsen
dc.typeArtigo
unesp.author.orcid0000-0002-0285-8700[1]
unesp.author.orcid0000-0003-0927-3825[2]
unesp.author.orcid0000-0002-1891-9563[4]
unesp.author.orcid0000-0003-0008-9079[5]

Arquivos

Coleções

Artigos