ArticleNature communications2023
A multiplexed bacterial two-hybrid for rapid characterization of protein-protein interactions and iterative protein design.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Antibody Affinity Maturation by Yeast Mating against a Diverse Antigen Library Enhances Antibody Resistance to Viral Mutations.ACS pharmacology & translational science · 2026Article
- Accelerating protein design by scaling experimental characterization.Nature communications · 2026Article
- Detection of Protein-Protein Interactions in Escherichia coli With Single Molecule Sensitivity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- InsiliCoil: An Integrated Software Suite for Coiled Coil Design, Prediction, and Therapeutic Engineering.ACS synthetic biology · 2026Article
- Optimized Quantitative Bacterial Two-Hybrid (qB2H) for Protein-Protein Interaction Assessment.Computational and structural biotechnology journal · 2026Article
- Bacterial two-hybrid systems evolved: innovations for protein-protein interaction research.Journal of bacteriology · 2025Review
- De novo designed protein guiding targeted protein degradation.Nature communications · 2025Article
- Massively parallel measurement of protein-protein interactions by sequencing using MP3-seq.Nature chemical biology · 2024Article
- The art of designed coiled-coils for the regulation of mammalian cells.Cell chemical biology · 2024Review
- Discovering mechanisms of human genetic variation and controlling cell states at scale.Trends in genetics : TIG · 2024Review
- Preorganized cyclic modules facilitate the self-assembly of protein nanostructures.Chemical science · 2024Article
- MGPPI: multiscale graph neural networks for explainable protein-protein interaction prediction.Frontiers in genetics · 2024Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Protein-protein interactions (PPIs) are crucial for biological functions and have applications ranging from drug design to synthetic cell circuits. Coiled-coils have been used as a model to study the sequence determinants of specificity. However, building well-behaved sets of orthogonal pairs of coiled-coils remains challenging due to inaccurate predictions of orthogonality and difficulties in testing at scale. To address this, we develop the next-generation bacterial two-hybrid (NGB2H) method, which allows for the rapid exploration of interactions of programmed protein libraries in a quantitative and scalable way using next-generation sequencing readout. We design, build, and test large sets of orthogonal synthetic coiled-coils, assayed over 8,000 PPIs, and used the dataset to train a more accurate coiled-coil scoring algorithm (iCipa). After characterizing nearly 18,000 new PPIs, we identify to the best of our knowledge the largest set of orthogonal coiled-coils to date, with fifteen on-target interactions. Our approach provides a powerful tool for the design of orthogonal PPIs.
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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.