The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Ankh‐Score Produces Better Sequence Alignments Than AlphaFold3
Open accessPublished version of a preprint
Abstract
Protein sequence alignment is one of the most fundamental procedures in bioinformatics. Due to its many downstream applications, improvements to this procedure are of great importance. We consider two revolutionary concepts that emerged recently as candidates for improving the state‐of‐the‐art alignment methods: AlphaFold and protein language models such as Ankh, ProtT5, or ESM‐C. Alignment improvements can come from the structural alignment of AlphaFold‐predicted structures or the scoring based on the similarity of protein embeddings produced by the protein language models. Thorough comparison on many domains from BAliBASE and CDD demonstrates that the Ankh‐score method produces much better sequence alignments than the structural alignments using US‐align of AlphaFold3‐predicted structures. Both are better than the traditional method using BLOSUM matrices. This suggests that Ankh embeddings may possess certain information that is not available in the AlphaFold3‐predicted structures. The alignment software is freely available as a web server at e‐score.csd.uwo.ca and as source code at github.com/lucian‐ilie/E‐score .
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Cites
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 · cited 2×
“The first one is AlphaFold [1], which produced a much better solution to the fundamental problem of structure prediction, accelerating drug discovery, enzyme engineering, protein–protein interaction studies, etc. AlphaFold illuminated half of the dark human proteins [2].”
Accurate structure prediction of biomolecular interactions with AlphaFold 3
Abramson, J., Adler, J., Dunger, J., Evans, R., Green, T., Pritzel, A., Ronneberger, O., Willmore, L., Ballard, A. J., Bambrick, J., et al. (2024) · Nature · doi:10.1038/s41586-024-07487-w · Cited by 15,861 · cited 2×
“We present here a thorough comparison of the three methods: BLOSUM matrices [24], AlphaFold3 [25] (with US-align [26]), and Ankh-score [22, 23].”
Evolutionary-scale prediction of atomic level protein structure with a language model
Lin, Z., Akin, H., Rao, R., Hie, B., Zhu, Z., Lu, W., Smetanin, N., Verkuil, R., Kabeli, O., Shmueli, Y., et al. (2022) · doi:10.1101/2022.07.20.500902 · Cited by 5,990
Protein-level assembly increases protein sequence recovery from metagenomic samples manyfold
Steinegger, M., Mirdita, M., & Söding, J. (2019) · Nature Methods · doi:10.1038/s41592-019-0437-4 · Cited by 445 · cited 1×
“PLMs are trained on vast unlabelled sequence databases, such as UniProt [6] or BFD [7], to provide contextual representations for amino acid residues in the form of high-dimensional vectors, called embeddings, that capture functional and evolutionary patterns, helping to create state- of- the-art…”
Scoring alignments by embedding vector similarity
Ashrafzadeh, S., Golding, G. B., Ilie, S., & Ilie, L. (2023) · doi:10.1101/2023.08.30.555602 · Cited by 8 · cited 5×
“Precisely, the Ankh-score [22, 23] for two residues a 1 and a 2 is given by the cosine similarity between the vectors v i = Ankh ( a i ) , i = 1, 2 , computed by Ankh for the two residues, that is: We prove Ankh to be the best PLM for this task.”
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Research works printed but not linked: 33
- 10.1016/j.sbi.2022.102372 · DOI · Paper page
- 10.1109/TPAMI.2021.3095381 · DOI · Paper page
- 10.1126/science.ade2574 · DOI · Paper page
- Elnaggar A., 2023, Ankh: Optimized Protein Language Model Unlocks General‐Purpose Modelling, arXiv, 2301.06568 · arXiv
- 10.1093/nar/gkac1052 · DOI · Paper page
- 10.1038/s41586-019-1923-7 · DOI · Paper page
- 10.1073/pnas.1914677117 · DOI · Paper page
- 10.1038/s41467-021-23303-9 · DOI
- 10.1093/bioinformatics/btz595 · DOI
- 10.1093/bib/bbab502 · DOI
- 10.1093/bioinformatics/btad738 · DOI · Paper page
- 10.1016/j.jmb.2023.167963 · DOI
- 10.1016/j.sbi.2023.102539 · DOI
- 10.1002/prot.26392 · DOI
- 10.1016/0022-2836(70)90057-4 · DOI · Paper page
- 10.1016/0022-2836(82)90398-9 · DOI
- 10.1093/bioinformatics/btad579 · DOI
- McWhite C. D., 2023, Leveraging Protein Language Models for Accurate Multiple Sequence Alignments, Genome Research, 33, 1145
- 10.1186/s12859-024-05699-5 · DOI · Paper page
- 10.1093/bib/bbae178 · DOI
- 10.1016/j.csbj.2025.12.002 · DOI · Paper page
- 10.1073/pnas.89.22.10915 · DOI · Paper page
- 10.1093/nar/gki524 · DOI · Paper page
- 10.1002/prot.20527 · DOI
- 10.1093/nar/gku1221 · DOI
- 10.1038/s41592-022-01585-1 · DOI · Paper page
- 10.1093/bioinformatics/btr701 · DOI
- 10.1093/nargab/lqae150 · DOI · Paper page
- 10.1093/nar/gkac387 · DOI
- 10.1038/s41587-023-01773-0 · DOI · Paper page
- 10.1006/jmbi.2001.5080 · DOI
- 10.1093/nar/gky1130 · DOI
- DeLano W. L., 2002, Pymol: An Open‐Source Molecular Graphics Tool, CCP4 News Protein Crystallography, 40, 82
Metadata
- Authors
- Malec, J., Rusen, K., Golding, G. B., & Ilie, L.
- Affiliations
- Western University (CA)
- McMaster University (CA)
- Corresponding author
- Ilie, Lucian
- Venue
- Proteins: Structure, Function, and Bioinformatics
- Publisher
- Wiley
- Published
- 2026-05-03
- Volume
- 94
- Issue
- 10
- Pages
- 1631-1643
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- PMC
- PMC13539653
- OpenAlex
- W7160150235
- Cited by
- 1
- References
- 5
- Citations by year
- 2026: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada (RGPIN‐2021‐03978, RGPIN‐2020‐05733)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- protein sequence alignment, AlphaFold3, protein language models, structural alignment, alignment scoring, BAliBASE, CDD
- MeSH terms
- Algorithms, Amino Acid Sequence, Models, Molecular, Proteins, Software, Sequence Alignment, Protein Folding, Computational Biology, Sequence Analysis, Protein, Databases, Protein
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