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Inferring repeat-protein energetics from evolutionary information

Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing covariations in extant sequences. Still, many natural proteins that...

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Autores principales: Espada, Rocío, Parra, R. Gonzalo, Mora, Thierry, Walczak, Aleksandra M., Ferreiro, Diego U.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491312/
https://www.ncbi.nlm.nih.gov/pubmed/28617812
http://dx.doi.org/10.1371/journal.pcbi.1005584
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author Espada, Rocío
Parra, R. Gonzalo
Mora, Thierry
Walczak, Aleksandra M.
Ferreiro, Diego U.
author_facet Espada, Rocío
Parra, R. Gonzalo
Mora, Thierry
Walczak, Aleksandra M.
Ferreiro, Diego U.
author_sort Espada, Rocío
collection PubMed
description Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing covariations in extant sequences. Still, many natural proteins that fold into the same structural topology show different stabilization energies, and these are often related to their physiological behavior. We propose a description for the energetic variation given by sequence modifications in repeat proteins, systems for which the overall problem is simplified by their inherent symmetry. We explicitly account for single amino acid and pair-wise interactions and treat higher order correlations with a single term. We show that the resulting evolutionary field can be interpreted with structural detail. We trace the variations in the energetic scores of natural proteins and relate them to their experimental characterization. The resulting energetic evolutionary field allows the prediction of the folding free energy change for several mutants, and can be used to generate synthetic sequences that are statistically indistinguishable from the natural counterparts.
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spelling pubmed-54913122017-07-18 Inferring repeat-protein energetics from evolutionary information Espada, Rocío Parra, R. Gonzalo Mora, Thierry Walczak, Aleksandra M. Ferreiro, Diego U. PLoS Comput Biol Research Article Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing covariations in extant sequences. Still, many natural proteins that fold into the same structural topology show different stabilization energies, and these are often related to their physiological behavior. We propose a description for the energetic variation given by sequence modifications in repeat proteins, systems for which the overall problem is simplified by their inherent symmetry. We explicitly account for single amino acid and pair-wise interactions and treat higher order correlations with a single term. We show that the resulting evolutionary field can be interpreted with structural detail. We trace the variations in the energetic scores of natural proteins and relate them to their experimental characterization. The resulting energetic evolutionary field allows the prediction of the folding free energy change for several mutants, and can be used to generate synthetic sequences that are statistically indistinguishable from the natural counterparts. Public Library of Science 2017-06-15 /pmc/articles/PMC5491312/ /pubmed/28617812 http://dx.doi.org/10.1371/journal.pcbi.1005584 Text en © 2017 Espada et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Espada, Rocío
Parra, R. Gonzalo
Mora, Thierry
Walczak, Aleksandra M.
Ferreiro, Diego U.
Inferring repeat-protein energetics from evolutionary information
title Inferring repeat-protein energetics from evolutionary information
title_full Inferring repeat-protein energetics from evolutionary information
title_fullStr Inferring repeat-protein energetics from evolutionary information
title_full_unstemmed Inferring repeat-protein energetics from evolutionary information
title_short Inferring repeat-protein energetics from evolutionary information
title_sort inferring repeat-protein energetics from evolutionary information
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491312/
https://www.ncbi.nlm.nih.gov/pubmed/28617812
http://dx.doi.org/10.1371/journal.pcbi.1005584
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