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ProGen: Language Modeling for Protein Generation

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arxiv 2004.03497 v1 pith:KMYKXUJ2 submitted 2020-03-08 q-bio.BM cs.LGstat.ML

classification q-bio.BMcs.LGstat.ML
keywords proteinprogensequenceengineeringgenerationlanguagemodelingaccuracy
verification ladder T0 review T1 audit T2 compute T3 formal

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Generative modeling for protein engineering is key to solving fundamental problems in synthetic biology, medicine, and material science. We pose protein engineering as an unsupervised sequence generation problem in order to leverage the exponentially growing set of proteins that lack costly, structural annotations. We train a 1.2B-parameter language model, ProGen, on ~280M protein sequences conditioned on taxonomic and keyword tags such as molecular function and cellular component. This provides ProGen with an unprecedented range of evolutionary sequence diversity and allows it to generate with fine-grained control as demonstrated by metrics based on primary sequence similarity, secondary structure accuracy, and conformational energy.

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Forward citations

Cited by 19 Pith papers

Reviewed papers in the Pith corpus that reference this work. Sorted by Pith novelty score. OpenAlex reports about 34 citations worldwide. Full citation record

  1. DisProtEdit: Exploring Disentangled Representations for Multi-Attribute Protein Editing

    q-bio.QM 2025-06 conditional novelty 7.0 of 10

    DisProtEdit learns disentangled protein representations from separate structural and functional text descriptions, enabling controllable single- and multi-attribute protein editing via latent interpolation.

  2. Steering Protein Language Models

    q-bio.BM 2025-07 reject novelty 6.0 of 10

    Activation steering can guide protein language models to generate and optimize sequences with higher predicted thermostability, solubility, or GFP brightness, but only in surrogate-based evaluation.

  3. Protriever: End-to-End Differentiable Protein Homology Search for Fitness Prediction

    q-bio.QM 2025-06 conditional novelty 6.0 of 10

    Protriever trains a retriever and a protein language model together so the model learns which homologs to retrieve, reaching state-of-the-art zero-shot fitness prediction on ProteinGym with much faster retrieval.

  4. NbBench: Benchmarking Language Models for Comprehensive Nanobody Tasks

    cs.LG 2025-05 conditional novelty 6.0 of 10

    NbBench provides the first unified nanobody benchmark and shows that antibody language models lead on binding tasks while affinity and stability regressions remain hard for all tested models.

  5. An All-Atom Generative Model for Designing Protein Complexes

    cs.LG 2025-04 conditional novelty 6.0 of 10

    APM generates multi-chain protein complexes at all-atom resolution via a three-module flow-matching design, achieving strong computed binding affinities in antibody and peptide design benchmarks.

  6. Steering Protein Family Design through Profile Bayesian Flow

    q-bio.BM 2025-02 conditional novelty 6.0 of 10

    ProfileBFN adapts Bayesian flow networks to accept protein-family profiles, enabling diverse, novel, and apparently functional family protein generation from single-sequence training.

  7. Hotspot-Driven Peptide Design via Multi-Fragment Autoregressive Extension

    q-bio.BM 2024-11 conditional novelty 6.0 of 10

    PepHAR generates peptide binders by first sampling hot-spot residues from a learned energy model, then autoregressively extending fragments via dihedral angles, then refining the full structure.

  8. Preference-based Antibody Expression Ranking: Scaling with Large-scale Weak Supervision

    cs.LG 2026-06 conditional novelty 5.0 of 10

    A two-stage recipe — camelid-sequence continual pretraining plus DPO-style preference fine-tuning with weak positive pairs — improves antibody expression ranking over supervised baselines on an internal 1254-sequence ...

  9. Ankh3: Multi-Task Pretraining with Sequence Denoising and Completion Enhances Protein Representations

    cs.LG 2025-05 conditional novelty 5.0 of 10

    Ankh3 shows that combining multiple masking probabilities with sequence completion improves protein language model performance downstream, but the causal role of multi-task pretraining is not proven by a matched ablation.

  10. GLProtein: Global-and-Local Structure Aware Protein Representation Learning

    cs.LG 2025-05 conditional novelty 5.0 of 10

    GLProtein pre-trains a BERT-style protein model with triplet contrastive learning on structural similarity, 3D distance encoding, and substructure-based amino acid embeddings, improving contact and PPI prediction.

  11. Generative Artificial Intelligence in Bioinformatics: A Systematic Review of Models, Applications, and Methodological Advances

    cs.CL 2025-11 reject novelty 4.0 of 10

    Across the 68 papers it surveys, domain-specialized generative models usually outperform general-purpose LLMs on biological tasks, and agentic/conversational workflows are the least-covered topics.

  12. AnnoDPO: Protein Functional Annotation Learning with Direct Preference Optimization

    q-bio.BM 2025-06 reject novelty 4.0 of 10

    DPO with contrastive sequence-annotation alignment improves GO term prediction by 2 to 4 percent relative F1-Max over supervised fine-tuning alone.

  13. Protein Inverse Folding From Structure Feedback

    cs.LG 2025-06 conditional novelty 4.0 of 10

    DPO fine-tuning with ESMFold TM-Score preferences raises sequence recovery and predicted TM-Score of inverse folding models, and multi-round refinement produces large gains on hard targets.

  14. Towards More Accurate Full-Atom Antibody Co-Design

    q-bio.BM 2025-02 conditional novelty 4.0 of 10

    Igformer co-designs antibody CDR sequences and structures by adding personalized propagation, global attention, and dual equivariant message passing to dyMEAN, with modest benchmark improvements.

  15. DrugGen: Advancing Drug Discovery with Large Language Models and Reinforcement Learning Feedback

    q-bio.QM 2024-11 reject novelty 4.0 of 10

    A DrugGPT-derived model, fine-tuned on approved drugs and optimized with reinforcement learning, produces more valid molecules and higher purported binding affinities, though the affinity metric is the training reward.

  16. Open-Source Protein Language Models for Function Prediction and Protein Design

    cs.LG 2024-12 conditional novelty 3.0 of 10

    A 1M-sequence ProtBERT in DeepChem scores below the original 216M-sequence ProtBERT on all four benchmarks, and a VAE-based enzyme generation pilot yields candidates with low structural similarity to known plastic-deg...

  17. Aligning Large Language Models with Healthcare Stakeholders: A Pathway to Trustworthy AI Integration

    cs.CY 2025-05 conditional novelty 2.0 of 10

    A narrative review arguing that stakeholder involvement throughout LLM development and use is essential for trustworthy healthcare AI, with a taxonomy of applications and an outlook on regulation.

  18. A Comprehensive Review of Protein Language Models

    q-bio.BM 2025-02 conditional novelty 2.0 of 10

    A survey paper that catalogs protein language models, their architectures, training data, benchmarks, and tools, but lacks a systematic methodology and contains several factual errors.

  19. Leveraging Natural Language Processing to Unravel the Mystery of Life: A Review of NLP Approaches in Genomics, Transcriptomics, and Proteomics

    cs.CL 2025-06 unverdicted novelty 1.0 of 10

    A review maps how NLP architectures from word2vec to Evo 2 are applied to DNA, RNA, protein, and genome sequences, with tokenization and context choices shaping performance.

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