Surveying biomolecular frustration at atomic resolution

Autores
Chen, Mingchen; Chen, Xun; Schafer, Nicholas P.; Clementi, Cecilia; Komives, Elizabeth A.; Ferreiro, Diego; Wolynes, Peter G.
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To function, biomolecules require sufficient specificity of interaction as well as stability to live in the cell while still being able to move. Thermodynamic stability of only a limited number of specific structures is important so as to prevent promiscuous interactions. The individual interactions in proteins, therefore, have evolved collectively to give funneled minimally frustrated landscapes but some strategic parts of biomolecular sequences located at specific sites in the structure have been selected to be frustrated in order to allow both motion and interaction with partners. We describe a framework efficiently to quantify and localize biomolecular frustration at atomic resolution by examining the statistics of the energy changes that occur when the local environment of a site is changed. The location of patches of highly frustrated interactions correlates with key biological locations needed for physiological function. At atomic resolution, it becomes possible to extend frustration analysis to proteinligand complexes. At this resolution one sees that drug specificity is correlated with there being a minimally frustrated binding pocket leading to a funneled binding landscape. Atomistic frustration analysis provides a route for screening for more specific compounds for drug discovery
Fil: Chen, Mingchen. Rice University; Estados Unidos
Fil: Chen, Xun. Rice University; Estados Unidos
Fil: Schafer, Nicholas P.. Rice University; Estados Unidos
Fil: Clementi, Cecilia. Rice University; Estados Unidos
Fil: Komives, Elizabeth A.. University of California at San Diego; Estados Unidos
Fil: Ferreiro, Diego. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wolynes, Peter G.. Rice University; Estados Unidos
Materia
Protein Function
Local Frustration
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:11336/143211
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Surveying biomolecular frustration at atomic resolutionChen, MingchenChen, XunSchafer, Nicholas P.Clementi, CeciliaKomives, Elizabeth A.Ferreiro, DiegoWolynes, Peter G.Protein FunctionLocal Frustrationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1To function, biomolecules require sufficient specificity of interaction as well as stability to live in the cell while still being able to move. Thermodynamic stability of only a limited number of specific structures is important so as to prevent promiscuous interactions. The individual interactions in proteins, therefore, have evolved collectively to give funneled minimally frustrated landscapes but some strategic parts of biomolecular sequences located at specific sites in the structure have been selected to be frustrated in order to allow both motion and interaction with partners. We describe a framework efficiently to quantify and localize biomolecular frustration at atomic resolution by examining the statistics of the energy changes that occur when the local environment of a site is changed. The location of patches of highly frustrated interactions correlates with key biological locations needed for physiological function. At atomic resolution, it becomes possible to extend frustration analysis to proteinligand complexes. At this resolution one sees that drug specificity is correlated with there being a minimally frustrated binding pocket leading to a funneled binding landscape. Atomistic frustration analysis provides a route for screening for more specific compounds for drug discoveryFil: Chen, Mingchen. Rice University; Estados UnidosFil: Chen, Xun. Rice University; Estados UnidosFil: Schafer, Nicholas P.. Rice University; Estados UnidosFil: Clementi, Cecilia. Rice University; Estados UnidosFil: Komives, Elizabeth A.. University of California at San Diego; Estados UnidosFil: Ferreiro, Diego. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wolynes, Peter G.. Rice University; Estados UnidosNature2020-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/143211Chen, Mingchen; Chen, Xun; Schafer, Nicholas P.; Clementi, Cecilia; Komives, Elizabeth A.; et al.; Surveying biomolecular frustration at atomic resolution; Nature; Nature Communications; 11; 5944; 11-2020; 1-92041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41467-020-19560-9info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-020-19560-9info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:07:53Zoai:ri.conicet.gov.ar:11336/143211instacron: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 10:07:54.103CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Surveying biomolecular frustration at atomic resolution
title Surveying biomolecular frustration at atomic resolution
spellingShingle Surveying biomolecular frustration at atomic resolution
Chen, Mingchen
Protein Function
Local Frustration
title_short Surveying biomolecular frustration at atomic resolution
title_full Surveying biomolecular frustration at atomic resolution
title_fullStr Surveying biomolecular frustration at atomic resolution
title_full_unstemmed Surveying biomolecular frustration at atomic resolution
title_sort Surveying biomolecular frustration at atomic resolution
dc.creator.none.fl_str_mv Chen, Mingchen
Chen, Xun
Schafer, Nicholas P.
Clementi, Cecilia
Komives, Elizabeth A.
Ferreiro, Diego
Wolynes, Peter G.
author Chen, Mingchen
author_facet Chen, Mingchen
Chen, Xun
Schafer, Nicholas P.
Clementi, Cecilia
Komives, Elizabeth A.
Ferreiro, Diego
Wolynes, Peter G.
author_role author
author2 Chen, Xun
Schafer, Nicholas P.
Clementi, Cecilia
Komives, Elizabeth A.
Ferreiro, Diego
Wolynes, Peter G.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Protein Function
Local Frustration
topic Protein Function
Local Frustration
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv To function, biomolecules require sufficient specificity of interaction as well as stability to live in the cell while still being able to move. Thermodynamic stability of only a limited number of specific structures is important so as to prevent promiscuous interactions. The individual interactions in proteins, therefore, have evolved collectively to give funneled minimally frustrated landscapes but some strategic parts of biomolecular sequences located at specific sites in the structure have been selected to be frustrated in order to allow both motion and interaction with partners. We describe a framework efficiently to quantify and localize biomolecular frustration at atomic resolution by examining the statistics of the energy changes that occur when the local environment of a site is changed. The location of patches of highly frustrated interactions correlates with key biological locations needed for physiological function. At atomic resolution, it becomes possible to extend frustration analysis to proteinligand complexes. At this resolution one sees that drug specificity is correlated with there being a minimally frustrated binding pocket leading to a funneled binding landscape. Atomistic frustration analysis provides a route for screening for more specific compounds for drug discovery
Fil: Chen, Mingchen. Rice University; Estados Unidos
Fil: Chen, Xun. Rice University; Estados Unidos
Fil: Schafer, Nicholas P.. Rice University; Estados Unidos
Fil: Clementi, Cecilia. Rice University; Estados Unidos
Fil: Komives, Elizabeth A.. University of California at San Diego; Estados Unidos
Fil: Ferreiro, Diego. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wolynes, Peter G.. Rice University; Estados Unidos
description To function, biomolecules require sufficient specificity of interaction as well as stability to live in the cell while still being able to move. Thermodynamic stability of only a limited number of specific structures is important so as to prevent promiscuous interactions. The individual interactions in proteins, therefore, have evolved collectively to give funneled minimally frustrated landscapes but some strategic parts of biomolecular sequences located at specific sites in the structure have been selected to be frustrated in order to allow both motion and interaction with partners. We describe a framework efficiently to quantify and localize biomolecular frustration at atomic resolution by examining the statistics of the energy changes that occur when the local environment of a site is changed. The location of patches of highly frustrated interactions correlates with key biological locations needed for physiological function. At atomic resolution, it becomes possible to extend frustration analysis to proteinligand complexes. At this resolution one sees that drug specificity is correlated with there being a minimally frustrated binding pocket leading to a funneled binding landscape. Atomistic frustration analysis provides a route for screening for more specific compounds for drug discovery
publishDate 2020
dc.date.none.fl_str_mv 2020-11
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/11336/143211
Chen, Mingchen; Chen, Xun; Schafer, Nicholas P.; Clementi, Cecilia; Komives, Elizabeth A.; et al.; Surveying biomolecular frustration at atomic resolution; Nature; Nature Communications; 11; 5944; 11-2020; 1-9
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/143211
identifier_str_mv Chen, Mingchen; Chen, Xun; Schafer, Nicholas P.; Clementi, Cecilia; Komives, Elizabeth A.; et al.; Surveying biomolecular frustration at atomic resolution; Nature; Nature Communications; 11; 5944; 11-2020; 1-9
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/articles/s41467-020-19560-9
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-020-19560-9
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 Nature
publisher.none.fl_str_mv Nature
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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