Protein Fluctuations and Cavity Changes Relationship

Autores
Barletta Roldan, Patricio German; Fernández Alberti, Sebastián
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Protein cavities and tunnels are critical for function. Ligand recognition and binding, transport, and enzyme catalysis require cavities rearrangements. Therefore, the flexibility of cavities should be guaranteed by protein vibrational dynamics. Molecular dynamics simulations provide a framework to explore conformational plasticity of protein cavities. Herein, we present a novel procedure to characterize the dynamics of protein cavities in terms of their volume gradient vector. For this purpose, we make use of algorithms for calculation of the cavity volume that result robust for numerical differentiations. Volume gradient vector is expressed in terms of principal component analysis obtained from equilibrated molecular dynamics simulations. We analyze contributions of principal component modes to the volume gradient vector according to their frequency and degree of delocalization. In all our test cases, we find that low frequency modes play a critical role together with minor contributions of high frequency modes. These modes involve concerted motions of significant fractions of the total residues lining the cavities. We make use of variations of the potential energy of a protein in the direction of the volume gradient vector as a measure of flexibility of the cavity. We show that proteins whose collective low frequency fluctuations contribute the most to changes of cavity volume exhibit more flexible cavities.
Fil: Barletta Roldan, Patricio German. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fernández Alberti, Sebastián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
PROTEIN
CAVITY
DYNAMICS
PCA
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:11336/98559
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Protein Fluctuations and Cavity Changes RelationshipBarletta Roldan, Patricio GermanFernández Alberti, SebastiánPROTEINCAVITYDYNAMICSPCAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Protein cavities and tunnels are critical for function. Ligand recognition and binding, transport, and enzyme catalysis require cavities rearrangements. Therefore, the flexibility of cavities should be guaranteed by protein vibrational dynamics. Molecular dynamics simulations provide a framework to explore conformational plasticity of protein cavities. Herein, we present a novel procedure to characterize the dynamics of protein cavities in terms of their volume gradient vector. For this purpose, we make use of algorithms for calculation of the cavity volume that result robust for numerical differentiations. Volume gradient vector is expressed in terms of principal component analysis obtained from equilibrated molecular dynamics simulations. We analyze contributions of principal component modes to the volume gradient vector according to their frequency and degree of delocalization. In all our test cases, we find that low frequency modes play a critical role together with minor contributions of high frequency modes. These modes involve concerted motions of significant fractions of the total residues lining the cavities. We make use of variations of the potential energy of a protein in the direction of the volume gradient vector as a measure of flexibility of the cavity. We show that proteins whose collective low frequency fluctuations contribute the most to changes of cavity volume exhibit more flexible cavities.Fil: Barletta Roldan, Patricio German. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández Alberti, Sebastián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Chemical Society2018-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/98559Barletta Roldan, Patricio German; Fernández Alberti, Sebastián; Protein Fluctuations and Cavity Changes Relationship; American Chemical Society; Journal of Chemical Theory and Computation; 14; 2; 2-2018; 998-10081549-9618CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/10.1021/acs.jctc.7b00744info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jctc.7b00744info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:55Zoai:ri.conicet.gov.ar:11336/98559instacron: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 09:38:55.6CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Protein Fluctuations and Cavity Changes Relationship
title Protein Fluctuations and Cavity Changes Relationship
spellingShingle Protein Fluctuations and Cavity Changes Relationship
Barletta Roldan, Patricio German
PROTEIN
CAVITY
DYNAMICS
PCA
title_short Protein Fluctuations and Cavity Changes Relationship
title_full Protein Fluctuations and Cavity Changes Relationship
title_fullStr Protein Fluctuations and Cavity Changes Relationship
title_full_unstemmed Protein Fluctuations and Cavity Changes Relationship
title_sort Protein Fluctuations and Cavity Changes Relationship
dc.creator.none.fl_str_mv Barletta Roldan, Patricio German
Fernández Alberti, Sebastián
author Barletta Roldan, Patricio German
author_facet Barletta Roldan, Patricio German
Fernández Alberti, Sebastián
author_role author
author2 Fernández Alberti, Sebastián
author2_role author
dc.subject.none.fl_str_mv PROTEIN
CAVITY
DYNAMICS
PCA
topic PROTEIN
CAVITY
DYNAMICS
PCA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Protein cavities and tunnels are critical for function. Ligand recognition and binding, transport, and enzyme catalysis require cavities rearrangements. Therefore, the flexibility of cavities should be guaranteed by protein vibrational dynamics. Molecular dynamics simulations provide a framework to explore conformational plasticity of protein cavities. Herein, we present a novel procedure to characterize the dynamics of protein cavities in terms of their volume gradient vector. For this purpose, we make use of algorithms for calculation of the cavity volume that result robust for numerical differentiations. Volume gradient vector is expressed in terms of principal component analysis obtained from equilibrated molecular dynamics simulations. We analyze contributions of principal component modes to the volume gradient vector according to their frequency and degree of delocalization. In all our test cases, we find that low frequency modes play a critical role together with minor contributions of high frequency modes. These modes involve concerted motions of significant fractions of the total residues lining the cavities. We make use of variations of the potential energy of a protein in the direction of the volume gradient vector as a measure of flexibility of the cavity. We show that proteins whose collective low frequency fluctuations contribute the most to changes of cavity volume exhibit more flexible cavities.
Fil: Barletta Roldan, Patricio German. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fernández Alberti, Sebastián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Protein cavities and tunnels are critical for function. Ligand recognition and binding, transport, and enzyme catalysis require cavities rearrangements. Therefore, the flexibility of cavities should be guaranteed by protein vibrational dynamics. Molecular dynamics simulations provide a framework to explore conformational plasticity of protein cavities. Herein, we present a novel procedure to characterize the dynamics of protein cavities in terms of their volume gradient vector. For this purpose, we make use of algorithms for calculation of the cavity volume that result robust for numerical differentiations. Volume gradient vector is expressed in terms of principal component analysis obtained from equilibrated molecular dynamics simulations. We analyze contributions of principal component modes to the volume gradient vector according to their frequency and degree of delocalization. In all our test cases, we find that low frequency modes play a critical role together with minor contributions of high frequency modes. These modes involve concerted motions of significant fractions of the total residues lining the cavities. We make use of variations of the potential energy of a protein in the direction of the volume gradient vector as a measure of flexibility of the cavity. We show that proteins whose collective low frequency fluctuations contribute the most to changes of cavity volume exhibit more flexible cavities.
publishDate 2018
dc.date.none.fl_str_mv 2018-02
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/11336/98559
Barletta Roldan, Patricio German; Fernández Alberti, Sebastián; Protein Fluctuations and Cavity Changes Relationship; American Chemical Society; Journal of Chemical Theory and Computation; 14; 2; 2-2018; 998-1008
1549-9618
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98559
identifier_str_mv Barletta Roldan, Patricio German; Fernández Alberti, Sebastián; Protein Fluctuations and Cavity Changes Relationship; American Chemical Society; Journal of Chemical Theory and Computation; 14; 2; 2-2018; 998-1008
1549-9618
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://pubs.acs.org/doi/10.1021/acs.jctc.7b00744
info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jctc.7b00744
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
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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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