Exploring the Folding Mechanism of Dimeric Superoxide Dismutase

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dc.contributor.authorMouro, Paulo R. [UNESP]
dc.contributor.authorSanches, Murilo N. [UNESP]
dc.contributor.authorLeite, Vitor B. P. [UNESP]
dc.contributor.authorChahine, Jorge [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2023-07-29T16:04:43Z
dc.date.available2023-07-29T16:04:43Z
dc.date.issued2023-02-16
dc.description.abstractThe Cu/Zn Human Superoxide Dismutase (SOD1) is a dimeric metalloenzyme whose genetic mutations are directly related to amyotrophic lateral sclerosis (ALS), so understanding its folding mechanism is of fundamental importance. Currently, the SOD1 dimer formation is studied via molecular dynamics simulations using a simplified structure-based model and an all-atom model. Results from the simplified model reveal a mechanism dependent on distances between monomers, which are limited by constraints to mimic concentration dependence. The stability of intermediates (during the int state) is significantly affected by this distance, as well as by the presence of two folded monomers prior to dimer formation. The kinetics of interface formation are also highly dependent on the separation distance. The folding temperature of the dimer is about 4.2% higher than that of the monomer, a value not too different from experimental data. All-atom simulations on the apo dimer give binding free energy between monomers similar to experimental values. An intermediate state is evident for the apo form at a separation distance between monomers slightly larger than the native distance which has little formed interface between monomers. We have shown that this intermediate is stabilized by non-native intra- and intercontacts.en
dc.description.affiliationSão Paulo State University (UNESP)
dc.description.affiliationUnespSão Paulo State University (UNESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent1338-1349
dc.identifierhttp://dx.doi.org/10.1021/acs.jpcb.2c08877
dc.identifier.citationJournal of Physical Chemistry B, v. 127, n. 6, p. 1338-1349, 2023.
dc.identifier.doi10.1021/acs.jpcb.2c08877
dc.identifier.issn1520-5207
dc.identifier.issn1520-6106
dc.identifier.scopus2-s2.0-85147209701
dc.identifier.urihttp://hdl.handle.net/11449/249621
dc.language.isoeng
dc.relation.ispartofJournal of Physical Chemistry B
dc.sourceScopus
dc.titleExploring the Folding Mechanism of Dimeric Superoxide Dismutaseen
dc.typeArtigo
unesp.author.orcid0000-0001-9650-7989[2]
unesp.author.orcid0000-0003-0008-9079[3]
unesp.author.orcid0000-0002-6474-0337[4]

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