dc.creatorMarcos, María Laura
dc.creatorEchave, Julián
dc.date.accessioned2018-07-11T20:01:00Z
dc.date.accessioned2018-11-06T16:21:08Z
dc.date.available2018-07-11T20:01:00Z
dc.date.available2018-11-06T16:21:08Z
dc.date.created2018-07-11T20:01:00Z
dc.date.issued2015-04
dc.identifierMarcos, 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.identifier2167-8359
dc.identifierhttp://hdl.handle.net/11336/51783
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1907340
dc.description.abstractIn 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.languageeng
dc.publisherPeerJ Inc
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.7717/peerj.911
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://peerj.com/articles/911/
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCONTACT DENSITY
dc.subjectPACKING
dc.subjectPROTEIN EVOLUTION
dc.subjectRATE VARIATION AMONG SITES
dc.subjectSIDE CHAIN
dc.subjectSTRUCTURAL CONSTRAINTS
dc.titleToo packed to change: Side-chain packing and site-specific substitution rates in protein evolution
dc.typeArtículos de revistas
dc.typeArtículos de revistas
dc.typeArtículos de revistas


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