Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution

Autores
Marcos, María Laura; Echave, Julián
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In protein evolution, due to functional and biophysical constraints, the rates of amino acid substitution differ from site to site. Among the best predictors of site-specific rates are solvent accessibility and packing density. The packing density measure that best correlates with rates is the weighted contact number (WCN), the sum of inverse square distances between a site's Ca and the Ca of the other sites. According to a mechanistic stress model proposed recently, rates are determined by packing because mutating packed sites stresses and destabilizes the protein's active conformation. While WCN is a measure of Ca packing, mutations replace side chains. Here, we consider whether a site's evolutionary divergence is constrained by main-chain packing or side-chain packing. To address this issue, we extended the stress theory to model side chains explicitly. The theory predicts that rates should depend solely on side-chain contact density. We tested this prediction on a data set of structurally and functionally diverse monomeric enzymes. We compared side-chain contact density with main-chain contact density measures and with relative solvent accessibility (RSA). We found that side-chain contact density is the best predictor of rate variation among sites (it explains 39.2% of the variation). Moreover, the independent contribution of main-chain contact density measures and RSA are negligible. Thus, as predicted by the stress theory, site-specific evolutionary rates are determined by side-chain packing.
Fil: Marcos, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Fil: Echave, Julián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Materia
CONTACT DENSITY
PACKING
PROTEIN EVOLUTION
RATE VARIATION AMONG SITES
SIDE CHAIN
STRUCTURAL CONSTRAINTS
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:11336/51783
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Too packed to change: Side-chain packing and site-specific substitution rates in protein evolutionMarcos, María LauraEchave, JuliánCONTACT DENSITYPACKINGPROTEIN EVOLUTIONRATE VARIATION AMONG SITESSIDE CHAINSTRUCTURAL CONSTRAINTShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1In protein evolution, due to functional and biophysical constraints, the rates of amino acid substitution differ from site to site. Among the best predictors of site-specific rates are solvent accessibility and packing density. The packing density measure that best correlates with rates is the weighted contact number (WCN), the sum of inverse square distances between a site's Ca and the Ca of the other sites. According to a mechanistic stress model proposed recently, rates are determined by packing because mutating packed sites stresses and destabilizes the protein's active conformation. While WCN is a measure of Ca packing, mutations replace side chains. Here, we consider whether a site's evolutionary divergence is constrained by main-chain packing or side-chain packing. To address this issue, we extended the stress theory to model side chains explicitly. The theory predicts that rates should depend solely on side-chain contact density. We tested this prediction on a data set of structurally and functionally diverse monomeric enzymes. We compared side-chain contact density with main-chain contact density measures and with relative solvent accessibility (RSA). We found that side-chain contact density is the best predictor of rate variation among sites (it explains 39.2% of the variation). Moreover, the independent contribution of main-chain contact density measures and RSA are negligible. Thus, as predicted by the stress theory, site-specific evolutionary rates are determined by side-chain packing.Fil: Marcos, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaFil: Echave, Julián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; ArgentinaPeerJ Inc2015-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/51783Marcos, María Laura; Echave, Julián; Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution; PeerJ Inc; PeerJ; 2015; 3; 4-2015; 1-122167-8359CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.7717/peerj.911info:eu-repo/semantics/altIdentifier/url/https://peerj.com/articles/911/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:47:54Zoai:ri.conicet.gov.ar:11336/51783instacron: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 10:47:54.734CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution
title Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution
spellingShingle Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution
Marcos, María Laura
CONTACT DENSITY
PACKING
PROTEIN EVOLUTION
RATE VARIATION AMONG SITES
SIDE CHAIN
STRUCTURAL CONSTRAINTS
title_short Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution
title_full Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution
title_fullStr Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution
title_full_unstemmed Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution
title_sort Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution
dc.creator.none.fl_str_mv Marcos, María Laura
Echave, Julián
author Marcos, María Laura
author_facet Marcos, María Laura
Echave, Julián
author_role author
author2 Echave, Julián
author2_role author
dc.subject.none.fl_str_mv CONTACT DENSITY
PACKING
PROTEIN EVOLUTION
RATE VARIATION AMONG SITES
SIDE CHAIN
STRUCTURAL CONSTRAINTS
topic CONTACT DENSITY
PACKING
PROTEIN EVOLUTION
RATE VARIATION AMONG SITES
SIDE CHAIN
STRUCTURAL CONSTRAINTS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In protein evolution, due to functional and biophysical constraints, the rates of amino acid substitution differ from site to site. Among the best predictors of site-specific rates are solvent accessibility and packing density. The packing density measure that best correlates with rates is the weighted contact number (WCN), the sum of inverse square distances between a site's Ca and the Ca of the other sites. According to a mechanistic stress model proposed recently, rates are determined by packing because mutating packed sites stresses and destabilizes the protein's active conformation. While WCN is a measure of Ca packing, mutations replace side chains. Here, we consider whether a site's evolutionary divergence is constrained by main-chain packing or side-chain packing. To address this issue, we extended the stress theory to model side chains explicitly. The theory predicts that rates should depend solely on side-chain contact density. We tested this prediction on a data set of structurally and functionally diverse monomeric enzymes. We compared side-chain contact density with main-chain contact density measures and with relative solvent accessibility (RSA). We found that side-chain contact density is the best predictor of rate variation among sites (it explains 39.2% of the variation). Moreover, the independent contribution of main-chain contact density measures and RSA are negligible. Thus, as predicted by the stress theory, site-specific evolutionary rates are determined by side-chain packing.
Fil: Marcos, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
Fil: Echave, Julián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
description In protein evolution, due to functional and biophysical constraints, the rates of amino acid substitution differ from site to site. Among the best predictors of site-specific rates are solvent accessibility and packing density. The packing density measure that best correlates with rates is the weighted contact number (WCN), the sum of inverse square distances between a site's Ca and the Ca of the other sites. According to a mechanistic stress model proposed recently, rates are determined by packing because mutating packed sites stresses and destabilizes the protein's active conformation. While WCN is a measure of Ca packing, mutations replace side chains. Here, we consider whether a site's evolutionary divergence is constrained by main-chain packing or side-chain packing. To address this issue, we extended the stress theory to model side chains explicitly. The theory predicts that rates should depend solely on side-chain contact density. We tested this prediction on a data set of structurally and functionally diverse monomeric enzymes. We compared side-chain contact density with main-chain contact density measures and with relative solvent accessibility (RSA). We found that side-chain contact density is the best predictor of rate variation among sites (it explains 39.2% of the variation). Moreover, the independent contribution of main-chain contact density measures and RSA are negligible. Thus, as predicted by the stress theory, site-specific evolutionary rates are determined by side-chain packing.
publishDate 2015
dc.date.none.fl_str_mv 2015-04
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/11336/51783
Marcos, María Laura; Echave, Julián; Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution; PeerJ Inc; PeerJ; 2015; 3; 4-2015; 1-12
2167-8359
CONICET Digital
CONICET
url http://hdl.handle.net/11336/51783
identifier_str_mv Marcos, María Laura; Echave, Julián; Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution; PeerJ Inc; PeerJ; 2015; 3; 4-2015; 1-12
2167-8359
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.7717/peerj.911
info:eu-repo/semantics/altIdentifier/url/https://peerj.com/articles/911/
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
dc.publisher.none.fl_str_mv PeerJ Inc
publisher.none.fl_str_mv PeerJ Inc
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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