Frustration in physiology and molecular medicine

Autores
Parra, R. Gonzalo; Komives, Elizabeth A.; Wolynes, Peter G.; Ferreiro, Diego
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Molecules provide the ultimate language in terms of which physiology and pathology must be understood. Myriads of proteins participate in elaborate networks of interactions and perform chemical activities coordinating the life of cells. To perform these often amazing tasks, proteins must move and we must think of them as dynamic ensembles of three dimensional structures formed first by folding the polypeptide chains so as to minimize the conflicts between the interactions of their constituent amino acids. It is apparent however that, even when completely folded, not all conflicting interactions have been resolved so the structure remains ‘locally frustrated’. Over the last decades it has become clearer that this local frustration is not just a random accident but plays an essential part of the inner workings of protein molecules. We will review here the physical origins of the frustration concept and review evidence that local frustration is important for protein physiology, protein-protein recognition, catalysis and allostery. Also, we highlight examples showing how alterations in the local frustration patterns can be linked to distinct pathologies. Finally we explore the extensions of the impact of frustration in higher order levels of organization of systems including gene regulatory networks and the neural networks of the brain.
Fil: Parra, R. Gonzalo. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; España
Fil: Komives, Elizabeth A.. University of California at San Diego; Estados Unidos
Fil: Wolynes, Peter G.. Rice University; Estados Unidos
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
Materia
FOLDING
FUNCTION
EVOLUTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/281733
Acceder
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spelling Frustration in physiology and molecular medicineParra, R. GonzaloKomives, Elizabeth A.Wolynes, Peter G.Ferreiro, DiegoFOLDINGFUNCTIONEVOLUTIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Molecules provide the ultimate language in terms of which physiology and pathology must be understood. Myriads of proteins participate in elaborate networks of interactions and perform chemical activities coordinating the life of cells. To perform these often amazing tasks, proteins must move and we must think of them as dynamic ensembles of three dimensional structures formed first by folding the polypeptide chains so as to minimize the conflicts between the interactions of their constituent amino acids. It is apparent however that, even when completely folded, not all conflicting interactions have been resolved so the structure remains ‘locally frustrated’. Over the last decades it has become clearer that this local frustration is not just a random accident but plays an essential part of the inner workings of protein molecules. We will review here the physical origins of the frustration concept and review evidence that local frustration is important for protein physiology, protein-protein recognition, catalysis and allostery. Also, we highlight examples showing how alterations in the local frustration patterns can be linked to distinct pathologies. Finally we explore the extensions of the impact of frustration in higher order levels of organization of systems including gene regulatory networks and the neural networks of the brain.Fil: Parra, R. Gonzalo. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; EspañaFil: Komives, Elizabeth A.. University of California at San Diego; Estados UnidosFil: Wolynes, Peter G.. Rice University; Estados UnidosFil: 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; ArgentinaElsevier Science2025-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/281733Parra, R. Gonzalo; Komives, Elizabeth A.; Wolynes, Peter G.; Ferreiro, Diego; Frustration in physiology and molecular medicine; Elsevier Science; Molecular Aspects Of Medicine; 103; 6-2025; 1-290098-2997CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0098299725000263info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mam.2025.101362info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-11T12:37:21Zoai:ri.conicet.gov.ar:11336/281733instacron: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:34982026-03-11 12:37:21.679CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Frustration in physiology and molecular medicine
title Frustration in physiology and molecular medicine
spellingShingle Frustration in physiology and molecular medicine
Parra, R. Gonzalo
FOLDING
FUNCTION
EVOLUTION
title_short Frustration in physiology and molecular medicine
title_full Frustration in physiology and molecular medicine
title_fullStr Frustration in physiology and molecular medicine
title_full_unstemmed Frustration in physiology and molecular medicine
title_sort Frustration in physiology and molecular medicine
dc.creator.none.fl_str_mv Parra, R. Gonzalo
Komives, Elizabeth A.
Wolynes, Peter G.
Ferreiro, Diego
author Parra, R. Gonzalo
author_facet Parra, R. Gonzalo
Komives, Elizabeth A.
Wolynes, Peter G.
Ferreiro, Diego
author_role author
author2 Komives, Elizabeth A.
Wolynes, Peter G.
Ferreiro, Diego
author2_role author
author
author
dc.subject.none.fl_str_mv FOLDING
FUNCTION
EVOLUTION
topic FOLDING
FUNCTION
EVOLUTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Molecules provide the ultimate language in terms of which physiology and pathology must be understood. Myriads of proteins participate in elaborate networks of interactions and perform chemical activities coordinating the life of cells. To perform these often amazing tasks, proteins must move and we must think of them as dynamic ensembles of three dimensional structures formed first by folding the polypeptide chains so as to minimize the conflicts between the interactions of their constituent amino acids. It is apparent however that, even when completely folded, not all conflicting interactions have been resolved so the structure remains ‘locally frustrated’. Over the last decades it has become clearer that this local frustration is not just a random accident but plays an essential part of the inner workings of protein molecules. We will review here the physical origins of the frustration concept and review evidence that local frustration is important for protein physiology, protein-protein recognition, catalysis and allostery. Also, we highlight examples showing how alterations in the local frustration patterns can be linked to distinct pathologies. Finally we explore the extensions of the impact of frustration in higher order levels of organization of systems including gene regulatory networks and the neural networks of the brain.
Fil: Parra, R. Gonzalo. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; España
Fil: Komives, Elizabeth A.. University of California at San Diego; Estados Unidos
Fil: Wolynes, Peter G.. Rice University; Estados Unidos
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
description Molecules provide the ultimate language in terms of which physiology and pathology must be understood. Myriads of proteins participate in elaborate networks of interactions and perform chemical activities coordinating the life of cells. To perform these often amazing tasks, proteins must move and we must think of them as dynamic ensembles of three dimensional structures formed first by folding the polypeptide chains so as to minimize the conflicts between the interactions of their constituent amino acids. It is apparent however that, even when completely folded, not all conflicting interactions have been resolved so the structure remains ‘locally frustrated’. Over the last decades it has become clearer that this local frustration is not just a random accident but plays an essential part of the inner workings of protein molecules. We will review here the physical origins of the frustration concept and review evidence that local frustration is important for protein physiology, protein-protein recognition, catalysis and allostery. Also, we highlight examples showing how alterations in the local frustration patterns can be linked to distinct pathologies. Finally we explore the extensions of the impact of frustration in higher order levels of organization of systems including gene regulatory networks and the neural networks of the brain.
publishDate 2025
dc.date.none.fl_str_mv 2025-06
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/11336/281733
Parra, R. Gonzalo; Komives, Elizabeth A.; Wolynes, Peter G.; Ferreiro, Diego; Frustration in physiology and molecular medicine; Elsevier Science; Molecular Aspects Of Medicine; 103; 6-2025; 1-29
0098-2997
CONICET Digital
CONICET
url http://hdl.handle.net/11336/281733
identifier_str_mv Parra, R. Gonzalo; Komives, Elizabeth A.; Wolynes, Peter G.; Ferreiro, Diego; Frustration in physiology and molecular medicine; Elsevier Science; Molecular Aspects Of Medicine; 103; 6-2025; 1-29
0098-2997
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0098299725000263
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mam.2025.101362
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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 12.977003

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