Evolutionary Conserved Positions Define Protein Conformational Diversity

Autores
Saldaño, Tadeo Enrique; Monzón, Alexander; Parisi, Gustavo Daniel; Fernández Alberti, Sebastián
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix.
Fil: Saldaño, Tadeo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Monzón, Alexander. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Fernández Alberti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Materia
CONFORMATIONAL DIVERSITY
PROTEINS
EVOLUTION
DYNAMICS
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:11336/85767

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network_name_str CONICET Digital (CONICET)
spelling Evolutionary Conserved Positions Define Protein Conformational DiversitySaldaño, Tadeo EnriqueMonzón, AlexanderParisi, Gustavo DanielFernández Alberti, SebastiánCONFORMATIONAL DIVERSITYPROTEINSEVOLUTIONDYNAMICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix.Fil: Saldaño, Tadeo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Monzón, Alexander. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Fernández Alberti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaPublic Library of Science2016-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85767Saldaño, Tadeo Enrique; Monzón, Alexander; Parisi, Gustavo Daniel; Fernández Alberti, Sebastián; Evolutionary Conserved Positions Define Protein Conformational Diversity; Public Library of Science; Plos Computational Biology; 12; 3; 3-2016; 1-251553-734XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004775info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pcbi.1004775info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:24Zoai:ri.conicet.gov.ar:11336/85767instacron: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 10:01:24.988CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Evolutionary Conserved Positions Define Protein Conformational Diversity
title Evolutionary Conserved Positions Define Protein Conformational Diversity
spellingShingle Evolutionary Conserved Positions Define Protein Conformational Diversity
Saldaño, Tadeo Enrique
CONFORMATIONAL DIVERSITY
PROTEINS
EVOLUTION
DYNAMICS
title_short Evolutionary Conserved Positions Define Protein Conformational Diversity
title_full Evolutionary Conserved Positions Define Protein Conformational Diversity
title_fullStr Evolutionary Conserved Positions Define Protein Conformational Diversity
title_full_unstemmed Evolutionary Conserved Positions Define Protein Conformational Diversity
title_sort Evolutionary Conserved Positions Define Protein Conformational Diversity
dc.creator.none.fl_str_mv Saldaño, Tadeo Enrique
Monzón, Alexander
Parisi, Gustavo Daniel
Fernández Alberti, Sebastián
author Saldaño, Tadeo Enrique
author_facet Saldaño, Tadeo Enrique
Monzón, Alexander
Parisi, Gustavo Daniel
Fernández Alberti, Sebastián
author_role author
author2 Monzón, Alexander
Parisi, Gustavo Daniel
Fernández Alberti, Sebastián
author2_role author
author
author
dc.subject.none.fl_str_mv CONFORMATIONAL DIVERSITY
PROTEINS
EVOLUTION
DYNAMICS
topic CONFORMATIONAL DIVERSITY
PROTEINS
EVOLUTION
DYNAMICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix.
Fil: Saldaño, Tadeo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Monzón, Alexander. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Fernández Alberti, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
description Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix.
publishDate 2016
dc.date.none.fl_str_mv 2016-03
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/11336/85767
Saldaño, Tadeo Enrique; Monzón, Alexander; Parisi, Gustavo Daniel; Fernández Alberti, Sebastián; Evolutionary Conserved Positions Define Protein Conformational Diversity; Public Library of Science; Plos Computational Biology; 12; 3; 3-2016; 1-25
1553-734X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/85767
identifier_str_mv Saldaño, Tadeo Enrique; Monzón, Alexander; Parisi, Gustavo Daniel; Fernández Alberti, Sebastián; Evolutionary Conserved Positions Define Protein Conformational Diversity; Public Library of Science; Plos Computational Biology; 12; 3; 3-2016; 1-25
1553-734X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pcbi.1004775
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/
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application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of 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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