{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T22:20:36Z","timestamp":1784672436216,"version":"3.55.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Models of molecular evolution aim at describing the evolutionary processes at the molecular level. However, current models rarely incorporate information from protein structure. Conversely, structure-based models of protein evolution have not been commonly applied to simulate sequence evolution in a phylogenetic framework, and they often ignore relevant evolutionary processes such as recombination. A simulation evolutionary framework that integrates substitution models that account for protein structure stability should be able to generate more realistic in silico evolved proteins for a variety of purposes.<\/jats:p><jats:p>Results: We developed a method to simulate protein evolution that combines models of protein folding stability, such that the fitness depends on the stability of the native state both with respect to unfolding and misfolding, with phylogenetic histories that can be either specified by the user or simulated with the coalescent under complex evolutionary scenarios, including recombination, demographics and migration. We have implemented this framework in a computer program called ProteinEvolver. Remarkably, comparing these models with empirical amino acid replacement models, we found that the former produce amino acid distributions closer to distributions observed in real protein families, and proteins that are predicted to be more stable. Therefore, we conclude that evolutionary models that consider protein stability and realistic evolutionary histories constitute a better approximation of the real evolutionary process.<\/jats:p><jats:p>Availability: \u00a0ProteinEvolver is written in C, can run in parallel and is freely available from http:\/\/code.google.com\/p\/proteinevolver\/.<\/jats:p><jats:p>Contact: \u00a0marenas@cbm.uam.es<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt530","type":"journal-article","created":{"date-parts":[[2013,9,14]],"date-time":"2013-09-14T00:19:01Z","timestamp":1379117941000},"page":"3020-3028","source":"Crossref","is-referenced-by-count":51,"title":["Protein evolution along phylogenetic histories under structurally constrained substitution models"],"prefix":"10.1093","volume":"29","author":[{"given":"Miguel","family":"Arenas","sequence":"first","affiliation":[{"name":"1 Centre for Molecular Biology \u2018Severo Ochoa\u2019, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Madrid, Spain and 2Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena G.","family":"Dos Santos","sequence":"additional","affiliation":[{"name":"1 Centre for Molecular Biology \u2018Severo Ochoa\u2019, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Madrid, Spain and 2Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Posada","sequence":"additional","affiliation":[{"name":"1 Centre for Molecular Biology \u2018Severo Ochoa\u2019, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Madrid, Spain and 2Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugo","family":"Bastolla","sequence":"additional","affiliation":[{"name":"1 Centre for Molecular Biology \u2018Severo Ochoa\u2019, Consejo Superior de Investigaciones Cient\u00edficas (CSIC), Madrid, Spain and 2Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,9,12]]},"reference":[{"key":"2023012810492556000_btt530-B1","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1093\/bioinformatics\/bti263","article-title":"ProtTest: selection of best-fit models of protein evolution","volume":"21","author":"Abascal","year":"2005","journal-title":"Bioinformatics"},{"key":"2023012810492556000_btt530-B2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/sj.hdy.6801052","article-title":"The quest for natural selection in the age of comparative genomics","volume":"99","author":"Anisimova","year":"2007","journal-title":"Heredity"},{"key":"2023012810492556000_btt530-B3","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1093\/genetics\/164.3.1229","article-title":"Effect of recombination on the accuracy of the likelihood method for detecting positive selection at amino acid sites","volume":"164","author":"Anisimova","year":"2003","journal-title":"Genetics"},{"key":"2023012810492556000_btt530-B4","doi-asserted-by":"crossref","first-page":"e1000178","DOI":"10.1371\/journal.pcbi.1000178","article-title":"Identifying the important HIV-1 recombination breakpoints","volume":"4","author":"Archer","year":"2008","journal-title":"PLoS Comput. 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