2025/02/17 by Vijay Subramanian, Rajeswari Appadurai, H.N. Venkatesh +2 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · #Advanced Proteomics Techniques and Applications #Machine Learning in Bioinformatics #Ubiquitin and proteasome pathways
paper · pdf · doi:10.1101/2025.02.13.637956
openalex publication_date 2025/02/17 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/14
Abstract 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”. 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 provide a web server for Morpheus to test for metamorphic propensities for user-defined sequences ( http://mbu.iisc.ac.in/∼anand/morpheus ). Besides screening for metamorphic behaviour in proteomes, our work will be useful in de novo design and engineering of such proteins through further experimentation.