Mostrar el registro sencillo del ítem
dc.contributor.author
Marcos, María Laura
dc.contributor.author
Echave, Julián
dc.date.available
2018-07-11T20:01:00Z
dc.date.issued
2015-04
dc.identifier.citation
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
dc.identifier.issn
2167-8359
dc.identifier.uri
http://hdl.handle.net/11336/51783
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
PeerJ Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Contact Density
dc.subject
Packing
dc.subject
Protein Evolution
dc.subject
Rate Variation Among Sites
dc.subject
Side Chain
dc.subject
Structural Constraints
dc.subject.classification
Otras Ciencias Químicas
dc.subject.classification
Ciencias Químicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-07-11T18:09:07Z
dc.journal.volume
2015
dc.journal.number
3
dc.journal.pagination
1-12
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Marcos, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
dc.description.fil
Fil: Echave, Julián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina
dc.journal.title
PeerJ
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.7717/peerj.911
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://peerj.com/articles/911/
Archivos asociados