ArticleNature biotechnology2012
Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing.
Article in Nature biotechnology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
229 citing papers in PubMed, 382 citations in OpenAlex.
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- Using experimental results of protein design to guide biomolecular energy-function development.PLoS computational biology · 2026Article
- Small molecule-constrained paratope mimetic bicyclic peptides as potent inhibitors of group 1 and 2 influenza A virus hemagglutinins.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Potent Monoclonal Antibodies Against Circulating Yellow Fever Virus Strains from Donors Immunized with the 17D Vaccine.The American journal of tropical medicine and hygiene · 2026Article
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- De novo design of D-peptide ligands: Application to influenza virus hemagglutinin.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mapping the sclerostin-LRP4 binding interface identifies critical interaction hotspots in loops 1 and 3 of sclerostin.FEBS letters · 2025Article
- Epitope Mapping Using Yeast Display and Next Generation Sequencing.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Accurate de novo design of heterochiral protein-protein interactions.Cell research · 2024Article
- Preventing future zoonosis: SARS-CoV-2 mutations enhance human-animal cross-transmission.Computers in biology and medicine · 2024Article
- GGAssembler: Precise and economical design and synthesis of combinatorial mutation libraries.Protein science : a publication of the Protein Society · 2024Article
- Deep neural networks for predicting the affinity landscape of protein-protein interactions.iScience · 2024Article
- The JAK-STAT pathway: from structural biology to cytokine engineering.Signal transduction and targeted therapy · 2024Review
- Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
169 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
We show that comprehensive sequence-function maps obtained by deep sequencing can be used to reprogram interaction specificity and to leapfrog over bottlenecks in affinity maturation by combining many individually small contributions not detectable in conventional approaches. We use this approach to optimize two computationally designed inhibitors against H1N1 influenza hemagglutinin and, in both cases, obtain variants with subnanomolar binding affinity. The most potent of these, a 51-residue protein, is broadly cross-reactive against all influenza group 1 hemagglutinins, including human H2, and neutralizes H1N1 viruses with a potency that rivals that of several human monoclonal antibodies, demonstrating that computational design followed by comprehensive energy landscape mapping can generate proteins with potential therapeutic utility.
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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.