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Endowing protein language models with structural knowledge

2025· article· en· W4415683348 on OpenAlexfundno aff
Philip Hartout, Dexiong Chen, Paolo Pellizzoni, Carlos Oliver, Karsten Borgwardt

Bibliographic record

VenueBioinformatics · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicBiomedical Text Mining and Ontologies
Canadian institutionsnot available
FundersInstituto de Ciencias del Mar y Limnología, Universidad Nacional Autónoma de MéxicoInstitute for Catastrophic Loss Reduction
KeywordsCode (set theory)SoftwareSource codeKnowledge representation and reasoningNatural languageLanguage model

Abstract

fetched live from OpenAlex

MOTIVATION: Protein language models (PLMs) have transformed protein research by learning rich representations from sequence data alone, yet they largely ignore the wealth of structural information now available through advances in structure prediction. Current methods that incorporate structural data often require substantial computational resources and complex architectures, limiting their practical adoption. We present a novel joint sequence and structure embedding method that achieves computational and parameter efficiency while maintaining high performance. Our approach introduces a lightweight integration framework that combines pretrained sequence transformers' self-attention with specialized structural adapters, enabling seamless incorporation of structural knowledge into existing PLMs through these enhanced self-attention mechanisms. RESULTS: The method demonstrates remarkable efficiency, requiring only modest pretraining on 542K protein structures, three orders of magnitude less than the data used to train PLMs, using standard masked language modeling objectives. Despite this lightweight approach, our joint embeddings consistently outperform sequence-only models like ESM-2 while achieving comparable results to more complex structure-based methods that use significantly more parameters and computational resources. This work establishes a new paradigm for protein representation learning that balances performance with practical constraints. By providing computationally efficient joint sequence-structure embeddings, we offer the scientific community an accessible tool that captures both sequential and structural protein information without the computational overhead typically associated with structure-aware models. AVAILABILITY AND IMPLEMENTATION: code and links to checkpoints are available at https://github.com/BorgwardtLab/PST.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.838
Threshold uncertainty score0.311

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.268
Teacher spread0.257 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designOther design
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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