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Multiple Protein Structure Alignment at Scale with FoldMason
Open accessPreprint — published as 10.1126/science.ads6733 · Paper page
Abstract
Protein structure is conserved beyond sequence, making multiple structural alignment (MSTA) essential for analyzing distantly related proteins. Computational prediction methods have vastly extended our repository of available proteins structures, requiring fast and accurate MSTA methods. Here, we introduce FoldMason, a progressive MSTA method that leverages the structural alphabet from Foldseek, a pairwise structural aligner, for multiple alignment of hundreds of thousands of protein structures, exceeding alignment quality of state-of-the-art methods, while two orders of magnitudes faster than other MSTA methods. FoldMason computes confidence scores, offers interactive visualizations, and provides essential speed and accuracy for large-scale protein structure analysis in the era of accurate structure prediction. Using Flaviviridae glycoproteins, we demonstrate how FoldMason’s MSTAs support phylogenetic analysis below the twilight zone. FoldMason is free open-source software: foldmason.foldseek.com and webserver: search.foldseek.com/foldmason .
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764
Self-citationVaradi, M., Bertoni, D., Magana, P., Paramval, U., Pidruchna, I., Radhakrishnan, M., Tsenkov, M., Nair, S., Mirdita, M., Yeo, J., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkad1011 · Cited by 2,052
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Metadata
- Authors
- Gilchrist, C. L. M., Mirdita, M., & Steinegger, M.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Steinegger, Martin
- Venue
- Science
- Publisher
- openRxiv
- Published
- 2024-08-01
- Volume
- 391
- Issue
- 6784
- Pages
- 485-488
- ISSN
- 0036-8075 (ISSN-L)
- OpenAlex
- W7126115639
- Cited by
- 117
- References
- 2
- Citations by year
- 2026: 56 · 2025: 57 · 2024: 4
- FWCI
- 115.74
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Seoul National University
- National Research Foundation of Korea (RS-2021-NR061659, 2020M3‐A9G7‐103933, RS-2024-00396026, RS-2023-00250470, RS-2021-NR056571)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- progressive alignment, Foldseek, TM-align, structural alignment, phylogenetic analysis, structural conservation, confidence scores, interactive visualization, open source software
- MeSH terms
- Glycoproteins, Phylogeny, Protein Conformation, Proteins, Software, Viral Envelope Proteins, Sequence Alignment, Flaviviridae, Computational Biology, Structural Homology, Protein
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