dc.creator | Marcos, María Laura | |
dc.creator | Echave, Julián | |
dc.date.accessioned | 2018-07-11T20:01:00Z | |
dc.date.accessioned | 2018-11-06T16:21:08Z | |
dc.date.available | 2018-07-11T20:01:00Z | |
dc.date.available | 2018-11-06T16:21:08Z | |
dc.date.created | 2018-07-11T20:01:00Z | |
dc.date.issued | 2015-04 | |
dc.identifier | 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 | 2167-8359 | |
dc.identifier | http://hdl.handle.net/11336/51783 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | http://repositorioslatinoamericanos.uchile.cl/handle/2250/1907340 | |
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.language | eng | |
dc.publisher | PeerJ Inc | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.7717/peerj.911 | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://peerj.com/articles/911/ | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
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.title | Too packed to change: Side-chain packing and site-specific substitution rates in protein evolution | |
dc.type | Artículos de revistas | |
dc.type | Artículos de revistas | |
dc.type | Artículos de revistas | |