On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

Autores
Grosso, Marcos Alberto; Kalstein, Adrian; Parisi, Gustavo Daniel; Roitberg, Adrián; Fernández Alberti, Sebastián
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.
Fil: Grosso, Marcos Alberto. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kalstein, Adrian. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roitberg, Adrián. University of Florida; Estados Unidos
Fil: Fernández Alberti, Sebastián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Conformational dynamics
Subspaces
Eigen values
Molecular conformation
Nuclear magnetic resonance
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:11336/98598
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/98598
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a proteinGrosso, Marcos AlbertoKalstein, AdrianParisi, Gustavo DanielRoitberg, AdriánFernández Alberti, SebastiánConformational dynamicsSubspacesEigen valuesMolecular conformationNuclear magnetic resonancehttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.Fil: Grosso, Marcos Alberto. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kalstein, Adrian. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roitberg, Adrián. University of Florida; Estados UnidosFil: Fernández Alberti, Sebastián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Institute of Physics2015-06info: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/11336/98598Grosso, Marcos Alberto; Kalstein, Adrian; Parisi, Gustavo Daniel; Roitberg, Adrián; Fernández Alberti, Sebastián; On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein; American Institute of Physics; Journal of Chemical Physics; 142; 24; 6-2015; 1-130021-9606CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://scitation.aip.org/content/aip/journal/jcp/142/24/10.1063/1.4922925info:eu-repo/semantics/altIdentifier/doi/10.1063/1.4922925info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:05:13Zoai:ri.conicet.gov.ar:11336/98598instacron: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 10:05:13.781CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein
title On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein
spellingShingle On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein
Grosso, Marcos Alberto
Conformational dynamics
Subspaces
Eigen values
Molecular conformation
Nuclear magnetic resonance
title_short On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein
title_full On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein
title_fullStr On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein
title_full_unstemmed On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein
title_sort On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein
dc.creator.none.fl_str_mv Grosso, Marcos Alberto
Kalstein, Adrian
Parisi, Gustavo Daniel
Roitberg, Adrián
Fernández Alberti, Sebastián
author Grosso, Marcos Alberto
author_facet Grosso, Marcos Alberto
Kalstein, Adrian
Parisi, Gustavo Daniel
Roitberg, Adrián
Fernández Alberti, Sebastián
author_role author
author2 Kalstein, Adrian
Parisi, Gustavo Daniel
Roitberg, Adrián
Fernández Alberti, Sebastián
author2_role author
author
author
author
dc.subject.none.fl_str_mv Conformational dynamics
Subspaces
Eigen values
Molecular conformation
Nuclear magnetic resonance
topic Conformational dynamics
Subspaces
Eigen values
Molecular conformation
Nuclear magnetic resonance
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.
Fil: Grosso, Marcos Alberto. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Kalstein, Adrian. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roitberg, Adrián. University of Florida; Estados Unidos
Fil: Fernández Alberti, Sebastián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.
publishDate 2015
dc.date.none.fl_str_mv 2015-06
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/11336/98598
Grosso, Marcos Alberto; Kalstein, Adrian; Parisi, Gustavo Daniel; Roitberg, Adrián; Fernández Alberti, Sebastián; On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein; American Institute of Physics; Journal of Chemical Physics; 142; 24; 6-2015; 1-13
0021-9606
CONICET Digital
CONICET
url http://hdl.handle.net/11336/98598
identifier_str_mv Grosso, Marcos Alberto; Kalstein, Adrian; Parisi, Gustavo Daniel; Roitberg, Adrián; Fernández Alberti, Sebastián; On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein; American Institute of Physics; Journal of Chemical Physics; 142; 24; 6-2015; 1-13
0021-9606
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://scitation.aip.org/content/aip/journal/jcp/142/24/10.1063/1.4922925
info:eu-repo/semantics/altIdentifier/doi/10.1063/1.4922925
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 Institute of Physics
publisher.none.fl_str_mv American Institute of Physics
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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