ArticleNature communications2026
Improved protein binder design using β-pairing targeted RFdiffusion.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Validation and analysis of 12,000 AI-driven CAR-T designs in the Bits to Binders competition.Molecular systems biology · 2026Article
- Latent generative search unlocks de novo design of untapped biomolecular interactions at scale.bioRxiv : the preprint server for biology · 2026Article
- Accelerating protein design by scaling experimental characterization.Nature communications · 2026Article
- Artificial Intelligence and Protein Design: A retrospective study on 20-year emerging trends and core research areas from bibliometric perspectives.Probiotics and antimicrobial proteins · 2026Article
- Artificial Intelligence for Discovery in Life Sciences.Bioconjugate chemistry · 2026Review
- Use of hydrogen deuterium exchange mass spectrometry in tandem with modern structural biology.The Biochemical journal · 2026Review
- Validation and analysis of 12,000 AI-driven CAR-T designs in thebioRxiv : the preprint server for biology · 2026Article
- Review
- ProteinDJ: A high-performance and modular protein design pipeline.Protein science : a publication of the Protein Society · 2026Article
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Assessment of generative de novo peptide design methods for G protein-coupled receptors.PloS one · 2026Article
- Article
- Sequence and structural determinants of efficaciousbioRxiv : the preprint server for biology · 2025Article
- Constrained Diffusion for Protein Design with Hard Structural Constraints.bioRxiv : the preprint server for biology · 2025Article
- High-Throughput De Novo Protein Design Yields Novel Immunomodulatory Agonists.bioRxiv : the preprint server for biology · 2025Article
- The Role of AI-Driven De Novo Protein Design in the Exploration of the Protein Functional Universe.Biology · 2025Review
- Emerging frontiers in protein structure prediction following the AlphaFold revolution.Journal of the Royal Society, Interface · 2025Review
- Article
- Atomically accurate de novo design of antibodies with RFdiffusion.bioRxiv : the preprint server for biology · 2025Article
- High-throughput protein binder discovery by rapid in vivo selection.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
30 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Designing proteins that bind with high affinity to hydrophilic protein target sites remains a challenging problem. Here we show that RFdiffusion can be conditioned to generate protein scaffolds that form geometrically matched extended β-sheets with target protein edge β-strands in which polar groups on the target are complemented with hydrogen bonding groups on the design. We use this approach to design binders against edge-strand target sites on KIT, PDGFRɑ, ALK-2, ALK-3, FCRL5, NRP1, and α-CTX, and obtain higher (pM to mid nM) affinities and success rates than unconditioned RFdiffusion. Despite sharing β-strand interactions, designs have high specificity, reflecting the precise customization of interacting β-strand geometry and additional designed binder-target interactions. A binder-KIT co-crystal structure is nearly identical to the design model, confirming the accuracy of the design approach. The ability to robustly generate binders to the hydrophilic interaction surfaces of exposed β-strands considerably increases the range of computational binder design.
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