{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T14:09:16Z","timestamp":1765721356754,"version":"3.48.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Functionally important \u2018fold-switching\u2019 proteins, which do not obey the classical folding dogma, are now thought to be widespread. Algorithms that can accurately annotate fold-switching proteins from sequence information can help uncover the true extent of the \u2018metamorphome\u2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we present Morpheus, a fragment-based classification approach, that works by analysing the diversity of structures within a query protein sequence. Morpheus exhaustively curates and uses fragment structural data from the Protein Data Bank as well as the AlphaFold Protein Structure Database. We employed our algorithm on 57 different proteomes consisting of a total of 601\u2009218 proteins and identified about 10% of these proteins with the ability to fold-switch. Additionally, we provide a web server for Morpheus to test for fold-switching propensities for user-defined sequences (http:\/\/mbu.iisc.ac.in\/\u223canand\/morpheus). Besides screening for fold-switching behaviour in proteomes, our work will be useful in de novo design and engineering of such proteins through further experimentation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>All codes used for fragment-picking analysis and the proteome-level prediction data for the 57 proteomes are publicly available on Zenodo (https:\/\/zenodo.org\/records\/14837336). The algorithm is also hosted within the web server (http:\/\/mbu.iisc.ac.in\/\u223canand\/morpheus).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf635","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T13:19:57Z","timestamp":1763731197000},"source":"Crossref","is-referenced-by-count":0,"title":["Morpheus: a fragment-based algorithm to predict fold-switching behaviour in proteins across proteomes"],"prefix":"10.1093","volume":"41","author":[{"given":"Vijay","family":"Subramanian","sequence":"first","affiliation":[{"name":"Indian Institute of Science Education and Research , Pune 411008,","place":["India"]},{"name":"Molecular Biophysics Unit, Indian Institute of Science , Bangalore 560012,","place":["India"]}]},{"given":"Rajeswari","family":"Appadurai","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit, Indian Institute of Science , Bangalore 560012,","place":["India"]},{"name":"Department of Biology, Indian Institute of Science, Education and Research , Tirupati 517619,","place":["India"]}]},{"given":"Harikrishnan","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"International Business Machine (IBM) , Bangalore 560071,","place":["India"]}]},{"given":"Ashok","family":"Sekhar","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit, Indian Institute of Science , Bangalore 560012,","place":["India"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-1511","authenticated-orcid":false,"given":"Anand","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Molecular Biophysics Unit, Indian Institute of Science , Bangalore 560012,","place":["India"]}]}],"member":"286","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"2025121409064690100_btaf635-B1","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1042\/bj1280737","article-title":"The formation and stabilization of protein 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