PLMSearch: Protein language model powers accurate and fast sequence search for remote homology
Open accessPublished version of a preprint
Abstract
Homologous protein search is one of the most commonly used methods for protein annotation and analysis. Compared to structure search, detecting distant evolutionary relationships from sequences alone remains challenging. Here we propose PLMSearch ( P rotein L anguage M odel), a homologous protein search method with only sequences as input. PLMSearch uses deep representations from a pre-trained protein language model and trains the similarity prediction model with a large number of real structure similarity. This enables PLMSearch to capture the remote homology information concealed behind the sequences. Extensive experimental results show that PLMSearch can search millions of query-target protein pairs in seconds like MMseqs2 while increasing the sensitivity by more than threefold, and is comparable to state-of-the-art structure search methods. In particular, unlike traditional sequence search methods, PLMSearch can recall most remote homology pairs with dissimilar sequences but similar structures. PLMSearch is freely available at https://dmiip.sjtu.edu.cn/PLMSearch .
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Flagged first, then by citations
- Authors
- Liu, W., Wang, Z., You, R., Xie, C., Wei, H., Xiong, Y., Yang, J., & Zhu, S.
- Affiliations
- Fudan University (CN)
- Nankai University (CN)
- Shanghai Jiao Tong University (CN)
- Shandong University (CN)
- Corresponding author
- Yang, Jianyi
- Zhu, Shanfeng
- Venue
- Nature Communications
- Published
- 2024-03-30
- Volume
- 15
- Issue
- 1
- Pages
- 2775-2775
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10981738
- OpenAlex
- W4393342758
- Cited by
- 96
- References
- 14
- Citations by year
- 2026: 36 · 2025: 42 · 2024: 18
- FWCI
- 13.07
- Type
- journal article
- Language
- en
- Update notices
- correction (2024-09-05)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (62272105)
- Science and Technology Commission of Shanghai Municipality (2018SHZDZX01)
- The ZJ Lab, the Shanghai Research Center for Brain Science and Brain-inspired Intelligence Technology, and Beijing Academy of Artificial Intelligence
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- remote homology detection, protein language models, protein annotation
- MeSH terms
- Algorithms, Biological Evolution, Proteins, Sequence Analysis, Protein, Molecular Sequence Annotation
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