{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:15:26Z","timestamp":1770286526011,"version":"3.49.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Engineering and Physical Sciences Research Council grant","award":["EP\/L016044\/1"],"award-info":[{"award-number":["EP\/L016044\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Co-evolution analysis can be used to accurately predict residue\u2013residue contacts from multiple sequence alignments. The introduction of machine-learning techniques has enabled substantial improvements in precision and a shift from predicting binary contacts to predict distances between pairs of residues. These developments have significantly improved the accuracy of de novo prediction of static protein structures. With AlphaFold2 lifting the accuracy of some predicted protein models close to experimental levels, structure prediction research will move on to other challenges. One of those areas is the prediction of more than one conformation of a protein. Here, we examine the potential of residue\u2013residue distance predictions to be informative of protein flexibility rather than simply static structure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We used DMPfold to predict distance distributions for every residue pair in a set of proteins that showed both rigid and flexible behaviour. Residue pairs that were in contact in at least one reference structure were classified as rigid, flexible or neither. The predicted distance distribution of each residue pair was analysed for local maxima of probability indicating the most likely distance or distances between a pair of residues. We found that rigid residue pairs tended to have only a single local maximum in their predicted distance distributions while flexible residue pairs more often had multiple local maxima. These results suggest that the shape of predicted distance distributions contains information on the rigidity or flexibility of a protein and its constituent residues.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab562","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T11:27:30Z","timestamp":1628681250000},"page":"65-72","source":"Crossref","is-referenced-by-count":14,"title":["Co-evolutionary distance predictions contain flexibility information"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3558-8396","authenticated-orcid":false,"given":"Dominik","family":"Schwarz","sequence":"first","affiliation":[{"name":"Department of Statistics, University of Oxford , Oxford OX1 3LB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Georges","sequence":"additional","affiliation":[{"name":"Department of Computational Engineering and Data Science, Large Molecule Research , Penzberg 82377, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Kelm","sequence":"additional","affiliation":[{"name":"Computer-Aided Drug Design, UCB Pharma , Slough SL1 3WE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiye","family":"Shi","sequence":"additional","affiliation":[{"name":"Computer-Aided Drug Design, UCB Pharma , Slough SL1 3WE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Vangone","sequence":"additional","affiliation":[{"name":"Department of Computational Engineering and Data Science, Large Molecule Research , Penzberg 82377, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-2252","authenticated-orcid":false,"given":"Charlotte M","family":"Deane","sequence":"additional","affiliation":[{"name":"Department of Statistics, University of Oxford , Oxford OX1 3LB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"2023020108391213400_btab562-B1","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1093\/bioinformatics\/btx781","article-title":"DNCON2: improved protein contact prediction using two-level deep convolutional neural networks","volume":"34","author":"Adhikari","year":"2018","journal-title":"Bioinformatics"},{"key":"2023020108391213400_btab562-B2","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1110\/ps.037473.108","article-title":"Dynameomics: large-scale assessment of native protein flexibility","volume":"17","author":"Benson","year":"2008","journal-title":"Protein Sci"},{"key":"2023020108391213400_btab562-B3","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2023020108391213400_btab562-B4","doi-asserted-by":"crossref","first-page":"W264","DOI":"10.1093\/nar\/gku270","article-title":"The DynaMine webserver: predicting protein dynamics from sequence","volume":"42","author":"Cilia","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023020108391213400_btab562-B5","doi-asserted-by":"crossref","first-page":"4296","DOI":"10.1021\/acs.jcim.0c00115","article-title":"Structure- and ligand-based virtual screening on DUD-E+: performance dependence on approximations to the binding pocket","volume":"60","author":"Cleves","year":"2020","journal-title":"J. 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