ArticleScience advances2016
Protein engineering by highly parallel screening of computationally designed variants.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- Mesostructured Water Enhances Stability of ProteinMPNN-Designed Ubiquitin-Fold Proteins.Journal of the American Chemical Society · 2026Article
- Improving engineered biological systems with electronics and microfluidics.Nature biotechnology · 2025Review
- Massively Parallel Screening of Toll/Interleukin-1 Receptor (TIR)-Derived Peptides Reveals Multiple Toll-Like Receptors (TLRs)-Targeting Immunomodulatory Peptides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Robust genome and cell engineering via in vitro and in situ circularized RNAs.Nature biomedical engineering · 2025Article
- What Strengthens Protein-Protein Interactions: Analysis and Applications of Residue Correlation Networks.Journal of molecular biology · 2023Article
- Ubiquitin Engineering for Interrogating the Ubiquitin-Proteasome System and Novel Therapeutic Strategies.Cells · 2023Review
- Protein engineering via sequence-performance mapping.Cell systems · 2023Review
- Machine learning-coupled combinatorial mutagenesis enables resource-efficient engineering of CRISPR-Cas9 genome editor activities.Nature communications · 2022Article
- SYNBIP: synthetic binding proteins for research, diagnosis and therapy.Nucleic acids research · 2022Article
- Insights Into the Properties, Biological Functions, and Regulation of USP21.Frontiers in pharmacology · 2022Review
- Recent advances in user-friendly computational tools to engineer protein function.Briefings in bioinformatics · 2021Review
- Fluorescent Protein Variants Generated by Reassembly between Skeleton and Chromophore.ACS omega · 2021Article
- CRISPR/Cas9-facilitated engineering with growth-coupled and sensor-guidedMetabolic engineering communications · 2019Article
- A PxL motif promotes timely cell cycle substrate dephosphorylation by the Cdc14 phosphatase.Nature structural & molecular biology · 2018Article
- Development of a Dual-Functional Hydrogel Using RGD and Anti-VEGF Aptamer.Macromolecular bioscience · 2017Article
- Article
- Site-specific inhibition of the small ubiquitin-like modifier (SUMO)-conjugating enzyme Ubc9 selectively impairs SUMO chain formation.The Journal of biological chemistry · 2017Article
- Data driven flexible backbone protein design.PLoS computational biology · 2017Article
- Global analysis of protein folding using massively parallel design, synthesis, and testing.Science (New York, N.Y.) · 2017Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current combinatorial selection strategies for protein engineering have been successful at generating binders against a range of targets; however, the combinatorial nature of the libraries and their vast undersampling of sequence space inherently limit these methods due to the difficulty in finely controlling protein properties of the engineered region. Meanwhile, great advances in computational protein design that can address these issues have largely been underutilized. We describe an integrated approach that computationally designs thousands of individual protein binders for high-throughput synthesis and selection to engineer high-affinity binders. We show that a computationally designed library enriches for tight-binding variants by many orders of magnitude as compared to conventional randomization strategies. We thus demonstrate the feasibility of our approach in a proof-of-concept study and successfully obtain low-nanomolar binders using in vitro and in vivo selection systems.
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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.