ArticlePLoS computational biology2026
Trainable subnetworks reveal insights into structure knowledge organization in protein language models.
Article in PLoS computational biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Deconvolving mutation effects on protein stability and function with disentangled protein language models.bioRxiv : the preprint server for biology · 2026Article
- Training bias and sequence alignments shape protein-peptide docking by AlphaFold and related methods.Protein science : a publication of the Protein Society · 2025Article
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4 authors.
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Abstract
Protein language models (PLMs) pretrained via a masked language modeling objective have proven effective across a range of structure-related tasks, including high-resolution structure prediction. However, it remains unclear to what extent these models factorize protein structural categories among their learned parameters. In this work, we introduce trainable subnetworks, which mask out the PLM weights responsible for language modeling performance on a structural category of proteins. We systematically trained 39 PLM subnetworks targeting both sequence- and residue-level features at varying degrees of resolution using annotations defined by the CATH taxonomy and secondary structure elements. Using these PLM subnetworks, we assessed how structural factorization in PLMs influences downstream structure prediction. Our results show that PLMs are highly sensitive to sequence-level features and can predominantly disentangle extremely coarse or fine-grained information. Furthermore, we observe that structure prediction is highly responsive to factorized PLM representations and that small changes in language modeling performance can significantly impair PLM-based structure prediction capabilities. Our work presents a framework for studying feature entanglement within pretrained PLMs and can be leveraged to improve the alignment of learned PLM representations with known biological concepts.
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