ArticleNature biotechnology2024
Efficient evolution of human antibodies from general protein language models.
Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 251 papers, 1 of them a synthesis that pooled it.
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Who cites it
251 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Current computational tools for protein lysine acylation site prediction.Briefings in bioinformatics · 2024Pooled it
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- Tokenizing loops of antibodies.mAbs · 2026Article
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- ASD: antigen-specific antibody database.mAbs · 2026Article
- Computational design and translational development of TCR-mimic scFv antibodies for peptide-HLA neoantigen targeting.npj drug discovery · 2026Review
- Machine learning-assisted directed evolution of plant Rubisco.Science advances · 2026Article
- Once yearly cell-based therapy for sustained and dose-tunable delivery of monoclonal antibodies.Science advances · 2026Article
- A p53Molecular therapy. Oncology · 2026Article
- Big Data and Artificial Intelligence in Cancer Drug Discovery: Promise, Challenges, and Emerging Opportunities.Cancers · 2026Review
- Sequence and structural determinants of efficacious de novo chimaeric antigen receptors.Nature biomedical engineering · 2026Article
- The Evolution of Artificial Intelligence in Antibody Design: From Structure-Based Engineering to Generative Models.Antibodies (Basel, Switzerland) · 2026Review
- Attribution assignment for deep-generative sequence models enables interpretability analysis using positive-only data.PLoS computational biology · 2026Article
- Ergothioneine: Biosynthesis, Molecular Mechanisms, Physiological Function, and Role in Disease.MedComm · 2026Review
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- InstructPLM-mu: protein fitness prediction from structure instructions.Briefings in bioinformatics · 2026Article
- Protein-DNA Binding Sites Prediction via Integrating Pretrained Large Language Models and Contrastive Learning.Interdisciplinary sciences, computational life sciences · 2026Article
- Applications of synthetic biology in biomedicine.Molecular biomedicine · 2026Review
- Computationally Evidence-Grounded Sequence-First Design of Peptide Binders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
191 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report that general protein language models can efficiently evolve human antibodies by suggesting mutations that are evolutionarily plausible, despite providing the model with no information about the target antigen, binding specificity or protein structure. We performed language-model-guided affinity maturation of seven antibodies, screening 20 or fewer variants of each antibody across only two rounds of laboratory evolution, and improved the binding affinities of four clinically relevant, highly mature antibodies up to sevenfold and three unmatured antibodies up to 160-fold, with many designs also demonstrating favorable thermostability and viral neutralization activity against Ebola and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudoviruses. The same models that improve antibody binding also guide efficient evolution across diverse protein families and selection pressures, including antibiotic resistance and enzyme activity, suggesting that these results generalize to many settings.
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