PLMAlign

• 2024.6.5 Update: We have uploaded the Dataset of PLMSearch & PLMAlign in Zenodo.

This is the implement of <b>PLMAlign</b>, a pairwise protein sequence alignment tool in "PLMSearch: Protein language model powers accurate and fast sequence search for remote homology". PLMAlign takes per-residue embeddings as input to obtain specific alignments and corresponding alignment scores.

Specifically, PLMAlign can achieve <b>local</b> and <b>global</b> alignment. The specific algorithm and parameters are similar to the SW and NW algorithms implemented by EMBL-EBI and pLM-BLAST. However, by converting a fixed substitution matrix into similarity calculated by the dot product of per-residue embeddings, PLMAlign is able to capture deep evolutionary information and perform better on remote homology protein pairs.

<div align=center><img src="example/figure/framework.png" width="100%" height="100%"/></div>

Quick links

• Webserver
• Requirements
• Data preparation
• Reproduce all our experiments
• Run PLMAlign locally
• Citation

Webserver

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PLMAlign web server : dmiip.sjtu.edu.cn/PLMAlign :airplane:

PLMSearch web server : dmiip.sjtu.edu.cn/PLMSearch 🚀

PLMSearch source code : github.com/maovshao/PLMSearch :helicopter:

Requirements

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Follow the steps in requirements.sh

Data preparation

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We have released our experiment data, which can be downloaded from plmalign_data or Zenodo.

# Use the following command or download it from https://zenodo.org/records/11480660
wget https://dmiip.sjtu.edu.cn/PLMAlign/static/download/plmalign_data.tar.gz
tar zxvf plmalign_data.tar.gz

Reproduce all our experiments

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Reproduce all our experiments with good visualization by following the steps in:

• Malidup: malidup.ipynb
• Malisam: malisam.ipynb

Notice: Detailed results are saved in data/alignment_benchmark/result/.

• SCOPe40: scope40.ipynb

Notice: Detailed results are saved in data/scope40_test/output/.

Run PLMAlign locally

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• Run PLMAlign locally by following the example in pipeline.ipynb

Notice: the inputs and outputs of the example are saved in example/.

Citation

<span id="citation"></span> Liu, W., Wang, Z., You, R. et al. PLMSearch: Protein language model powers accurate and fast sequence search for remote homology. Nat Commun 15, 2775 (2024). https://doi.org/10.1038/s41467-024-46808-5

Liu, W. et al. (2025). PLMSearch and PLMAlign: Protein Language Model (PLM)-Based Homologous Protein Sequence Search and Alignment. In: KC, D.B. (eds) Large Language Models (LLMs) in Protein Bioinformatics. Methods in Molecular Biology, vol 2941. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-4623-6_14