How natural sequence variation modulates protein folding dynamics

Autores
Galpern, Ezequiel Alejandro; Roman, Ernesto Andres; Ferreiro, Diego
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Natural protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use sequence information to go beyond predicting native structures and global stability to infer the folding dynamics of globular proteins. The one- and two-body evolutionary energy fields at the amino-acid level are mapped to a coarse-grained description of folding, where proteins are divided into contiguous folding elements, commonly referred to as foldons. For 15 diverse protein families, we calculated the folding dynamics of hundreds of proteins by simulating an Ising chain of foldons, with their energetics determined by the amino acid sequences. We show that protein topology imposes limits on the variability of folding cooperativity within a family. While most beta and alpha/beta structures exhibit only a few possible mechanisms despite high sequence diversity, alpha topologies allow for diverse folding scenarios among family members. We show that both the stability and cooperativity changes induced by mutations can be computed directly using sequence-based evolutionary models.
Fil: Galpern, Ezequiel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Fisiología de Proteínas; Argentina
Fil: Roman, Ernesto Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Ferreiro, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Fisiología de Proteínas; Argentina
Materia
EVOLUTION
FOLDING MECHANISM
COOPERATIVITY
FOLDON
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:11336/262894
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling How natural sequence variation modulates protein folding dynamicsGalpern, Ezequiel AlejandroRoman, Ernesto AndresFerreiro, DiegoEVOLUTIONFOLDING MECHANISMCOOPERATIVITYFOLDONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Natural protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use sequence information to go beyond predicting native structures and global stability to infer the folding dynamics of globular proteins. The one- and two-body evolutionary energy fields at the amino-acid level are mapped to a coarse-grained description of folding, where proteins are divided into contiguous folding elements, commonly referred to as foldons. For 15 diverse protein families, we calculated the folding dynamics of hundreds of proteins by simulating an Ising chain of foldons, with their energetics determined by the amino acid sequences. We show that protein topology imposes limits on the variability of folding cooperativity within a family. While most beta and alpha/beta structures exhibit only a few possible mechanisms despite high sequence diversity, alpha topologies allow for diverse folding scenarios among family members. We show that both the stability and cooperativity changes induced by mutations can be computed directly using sequence-based evolutionary models.Fil: Galpern, Ezequiel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Fisiología de Proteínas; ArgentinaFil: Roman, Ernesto Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Ferreiro, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Fisiología de Proteínas; ArgentinaCornell University2024-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/262894Galpern, Ezequiel Alejandro; Roman, Ernesto Andres; Ferreiro, Diego; How natural sequence variation modulates protein folding dynamics; Cornell University; arXiv; 12-2024; 1-332331-8422CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.48550/arXiv.2412.14341info:eu-repo/semantics/altIdentifier/arxiv/https://arxiv.org/abs/2412.14341info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:49:02Zoai:ri.conicet.gov.ar:11336/262894instacron: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:34982025-09-29 09:49:02.709CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv How natural sequence variation modulates protein folding dynamics
title How natural sequence variation modulates protein folding dynamics
spellingShingle How natural sequence variation modulates protein folding dynamics
Galpern, Ezequiel Alejandro
EVOLUTION
FOLDING MECHANISM
COOPERATIVITY
FOLDON
title_short How natural sequence variation modulates protein folding dynamics
title_full How natural sequence variation modulates protein folding dynamics
title_fullStr How natural sequence variation modulates protein folding dynamics
title_full_unstemmed How natural sequence variation modulates protein folding dynamics
title_sort How natural sequence variation modulates protein folding dynamics
dc.creator.none.fl_str_mv Galpern, Ezequiel Alejandro
Roman, Ernesto Andres
Ferreiro, Diego
author Galpern, Ezequiel Alejandro
author_facet Galpern, Ezequiel Alejandro
Roman, Ernesto Andres
Ferreiro, Diego
author_role author
author2 Roman, Ernesto Andres
Ferreiro, Diego
author2_role author
author
dc.subject.none.fl_str_mv EVOLUTION
FOLDING MECHANISM
COOPERATIVITY
FOLDON
topic EVOLUTION
FOLDING MECHANISM
COOPERATIVITY
FOLDON
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Natural protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use sequence information to go beyond predicting native structures and global stability to infer the folding dynamics of globular proteins. The one- and two-body evolutionary energy fields at the amino-acid level are mapped to a coarse-grained description of folding, where proteins are divided into contiguous folding elements, commonly referred to as foldons. For 15 diverse protein families, we calculated the folding dynamics of hundreds of proteins by simulating an Ising chain of foldons, with their energetics determined by the amino acid sequences. We show that protein topology imposes limits on the variability of folding cooperativity within a family. While most beta and alpha/beta structures exhibit only a few possible mechanisms despite high sequence diversity, alpha topologies allow for diverse folding scenarios among family members. We show that both the stability and cooperativity changes induced by mutations can be computed directly using sequence-based evolutionary models.
Fil: Galpern, Ezequiel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Fisiología de Proteínas; Argentina
Fil: Roman, Ernesto Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Ferreiro, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Fisiología de Proteínas; Argentina
description Natural protein sequences serve as a natural record of the evolutionary constraints that shape their functional structures. We show that it is possible to use sequence information to go beyond predicting native structures and global stability to infer the folding dynamics of globular proteins. The one- and two-body evolutionary energy fields at the amino-acid level are mapped to a coarse-grained description of folding, where proteins are divided into contiguous folding elements, commonly referred to as foldons. For 15 diverse protein families, we calculated the folding dynamics of hundreds of proteins by simulating an Ising chain of foldons, with their energetics determined by the amino acid sequences. We show that protein topology imposes limits on the variability of folding cooperativity within a family. While most beta and alpha/beta structures exhibit only a few possible mechanisms despite high sequence diversity, alpha topologies allow for diverse folding scenarios among family members. We show that both the stability and cooperativity changes induced by mutations can be computed directly using sequence-based evolutionary models.
publishDate 2024
dc.date.none.fl_str_mv 2024-12
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/11336/262894
Galpern, Ezequiel Alejandro; Roman, Ernesto Andres; Ferreiro, Diego; How natural sequence variation modulates protein folding dynamics; Cornell University; arXiv; 12-2024; 1-33
2331-8422
CONICET Digital
CONICET
url http://hdl.handle.net/11336/262894
identifier_str_mv Galpern, Ezequiel Alejandro; Roman, Ernesto Andres; Ferreiro, Diego; How natural sequence variation modulates protein folding dynamics; Cornell University; arXiv; 12-2024; 1-33
2331-8422
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.48550/arXiv.2412.14341
info:eu-repo/semantics/altIdentifier/arxiv/https://arxiv.org/abs/2412.14341
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 Cornell University
publisher.none.fl_str_mv Cornell University
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 13.070432

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