ArticleNature structural & molecular biology2025
Computational design of sequence-specific DNA-binding proteins.
Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Hydrophobic Tag Protein Degraders: An Emerging Therapeutic Strategy for Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Accelerating protein design by scaling experimental characterization.Nature communications · 2026Article
- Article
- Distinct energetic blueprints diversify function of conserved protein folds.Nature chemistry · 2026Article
- Structure and evolution-guided design of minimal RNA-guided nucleases.Science (New York, N.Y.) · 2026Article
- Epigenetic editing approaches maturity: AI-driven precision design, delivery innovation, and the road to clinical translation.Clinical epigenetics · 2026Review
- Caveat emptor: predicting and modeling protein-DNA recognition and binding via machine-learning computational approaches.Nucleic acids research · 2026Review
- Tools For Building Artificial Biological Nanostructures.ACS nano · 2026Review
- Construction of synthetic protein-binding non-genetic DNA systems in living cells.Nature chemistry · 2026Article
- Reverse-engineering amyloid strains with generative protein design.bioRxiv : the preprint server for biology · 2026Article
- Exploiting plant immune "switches" for resistance engineering.Stress biology · 2026Review
- Protein FID: improved evaluation of protein structure generative models.Bioinformatics (Oxford, England) · 2026Article
- Review
- Structure and evolution-guided design of minimal RNA-guided nucleases.bioRxiv : the preprint server for biology · 2025Article
- Engineering the Link: From Genome Interaction Maps to Functional Insight.Advanced biology · 2025Review
- Article
- RNA sequence design and protein-DNA specificity prediction with NA-MPNN.bioRxiv : the preprint server for biology · 2025Article
- De novo design of RNA and nucleoprotein complexes.bioRxiv : the preprint server for biology · 2025Article
- Molecular circuits for genomic recording of cellular events.Trends in genetics : TIG · 2025Review
- Engineering a New Generation of Gene Editors: Integrating Synthetic Biology and AI Innovations.ACS synthetic biology · 2025Review
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20 authors.
Funding
Abstract
Sequence-specific DNA-binding proteins (DBPs) have critical roles in biology and biotechnology and there has been considerable interest in the engineering of DBPs with new or altered specificities for genome editing and other applications. While there has been some success in reprogramming naturally occurring DBPs using selection methods, the computational design of new DBPs that recognize arbitrary target sites remains an outstanding challenge. We describe a computational method for the design of small DBPs that recognize short specific target sequences through interactions with bases in the major groove and use this method to generate binders for five distinct DNA targets with mid-nanomolar to high-nanomolar affinities. The individual binding modules have specificity closely matching the computational models at as many as six base-pair positions and higher-order specificity can be achieved by rigidly positioning the binders along the DNA double helix using RFdiffusion. The crystal structure of a designed DBP-target site complex is in close agreement with the design model and the designed DBPs function in both Escherichia coli and mammalian cells to repress and activate transcription of neighboring genes. Our method provides a route to small and, hence, readily deliverable sequence-specific DBPs for gene regulation and editing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.