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Updated: Jul 16, 2025

A Protocol for Computer-Based Protein Structure and Function Prediction
Published on: November 3, 2011
pLM-BLAST: distant homology detection based on direct comparison of sequence representations from protein language
Kamil Kaminski1,2, Jan Ludwiczak1, Kamil Pawlicki1
1Institute of Evolutionary Biology, Faculty of Biology, Biological and Chemical Research Centre, University of Warsaw, Warsaw 02-089, Poland.
Motivation:
The detection of homology through sequence comparison is a typical first step in the study of protein function and evolution. In this work, we explore the applicability of protein language models to this task.
Results:
We introduce pLM-BLAST, a tool inspired by BLAST, that detects distant homology by comparing single-sequence representations (embeddings) derived from a protein language model, ProtT5. Our benchmarks reveal that pLM-BLAST maintains a level of accuracy on par with HHsearch for both highly similar sequences (with >50% identity) and markedly divergent sequences (with <30% identity), while being significantly faster. Additionally, pLM-BLAST stands out among other embedding-based tools due to its ability to compute local alignments. We show that these local alignments, produced by pLM-BLAST, often connect highly divergent proteins, thereby highlighting its potential to uncover previously undiscovered homologous relationships and improve protein annotation.
Availability And Implementation:
pLM-BLAST is accessible via the MPI Bioinformatics Toolkit as a web server for searching precomputed databases (https://toolkit.tuebingen.mpg.de/tools/plmblast). It is also available as a standalone tool for building custom databases and performing batch searches (https://github.com/labstructbioinf/pLM-BLAST).
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