biostudies-literatureUnknown41(12)Subramanian VWellcome Trust<h4>Motivation</h4>Functionally important 'fold-switching' 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 'metamorphome'.<h4>Results</h4>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 601 218 proteins and identified about 10% of these proteins with the ability to fold-switch. Additionally, we provBioinformatics (Oxford, England)btaf635https://www.ebi.ac.uk/biostudies/studies/S-EPMC12702140biostudies-literatureMorpheus: a fragment-based algorithm to predict fold-switching behaviour in proteins across proteomes.PMC12702140Subramanian VAppadurai RVenkatesh HSekhar ASrivastava AfalseMorpheus: a fragment-based algorithm to predict fold-switching behaviour in proteins across proteomes.<h4>Motivation</h4>Functionally important 'fold-switching' 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 'metamorphome'.<h4>Results</h4>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 601 218 proteins and identified about 10% of these proteins with the ability to fold-switch. Additionally, we prov2025-01-01T00:00:00Z2025 Dec2026-07-15T11:21:08.416Z2026-07-04T03:11:42.098ZS-EPMC127021404128492010.1093/bioinformatics/btaf635