Evidence map›Paper›PMID 28953867›Full record

ArticleNature2017

Massively parallel de novo protein design for targeted therapeutics.

Aaron Chevalier, Daniel-Adriano Silva, Gabriel J Rocklin, Derrick R Hicks, Renan Vergara, Patience Murapa, Steffen M Bernard, Lu Zhang, Kwok-Ho Lam, Guorui Yao and 18 more

Abstract read
In one paragraph

Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers.

0numbers the graph read from it
0cells of the map it votes in
242citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

242 citing papers in PubMed.

  1. Review
  2. Scalable Production of aPharmaceutics · 2026
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  4. RSC chemical biology · 2026
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  5. Materials today. Bio · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Computational design of an ultrapotent deltacoronavirus miniprotein inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article

182 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors.

Aaron ChevalierDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Daniel-Adriano SilvaDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Gabriel J RocklinDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Derrick R HicksDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Renan VergaraDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Patience MurapaDepartment of Microbiology, University of Washington, Seattle, Washington 98109, USA.
Steffen M BernardDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Lu ZhangState Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.
Kwok-Ho LamDepartment of Physiology and Biophysics, University of California, Irvine, California 92697, USA.
Guorui YaoDepartment of Physiology and Biophysics, University of California, Irvine, California 92697, USA.
Christopher D BahlDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Shin-Ichiro MiyashitaDepartment of Urology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Inna GoreshnikDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
James T FullerDepartment of Microbiology, University of Washington, Seattle, Washington 98109, USA.
Merika T KodayDepartment of Microbiology, University of Washington, Seattle, Washington 98109, USA.
Cody M JenkinsDepartment of Microbiology, University of Washington, Seattle, Washington 98109, USA.
Tom ColvinDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Lauren CarterDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Alan BohnDepartment of Microbiology, University of Washington, Seattle, Washington 98109, USA.
Cassie M BryanDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
D Alejandro Fernández-VelascoFacultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, México City 04510, Mexico.
Lance StewartInstitute for Protein Design, University of Washington, Seattle, Washington 98195, USA.
Min DongDepartment of Urology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Xuhui HuangDepartment of Chemistry and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Rongsheng JinDepartment of Physiology and Biophysics, University of California, Irvine, California 92697, USA.
Ian A WilsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Deborah H FullerDepartment of Microbiology, University of Washington, Seattle, Washington 98109, USA.
David BakerDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.

Funding

Overall EvaluationP41GM103403 · NIGMS · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2012 to 2017
$14.3M
Long-term effects of botulinum neurotoxins on neuronal viabilityR01NS080833 · NINDS · HARVARD MEDICAL SCHOOL · PI Min Dong · 2013 to 2026
$6.8M
MOLECULAR BASIS OF VIRAL PATHOGENESIST32AI007354 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI DE LA TORRE, JUAN C. · 1989 to 2020
$5.2M
Molecular mechanisms of botulinum neurotoxin neutralizationR01AI125704 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG, SHOEMAKER, CHARLES BIX · 2016 to 2020
$3.0M
Structural and functional studies of botulinum neurotoxinR01AI091823 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG · 2012 to 2016
$2.0M
Pixel Array Detector for Macromolecular CrystallographyS10OD021527 · OD · CORNELL UNIVERSITY · PI EALICK, STEVEN E · 2016 to 2016
$2.0M
Mucosally-delivered HA stem binding antiviral for influenzaR33AI119258 · NIAID · UNIVERSITY OF WASHINGTON · PI FULLER, DEBORAH H. · 2017 to 2019
$1.5M
Exploiting sites of vulnerability on influenza virusesR56AI117675 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2015 to 2015
$836k
Exploiting Vulnerability on Influenza VirusR56AI127371 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI WILSON, IAN A · 2017 to 2017
$730k
Mucosally-delivered HA stem binding antiviral for influenzaR21AI119258 · NIAID · UNIVERSITY OF WASHINGTON · PI FULLER, DEBORAH H. · 2015 to 2016
$477k
Structural mechanism for recognition of host receptor by botulinum neurotoxin AR21AI123920 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI JIN, RONGSHENG · 2016 to 2017
$425k
Optimization of a computationally designed antiviral for influenzaR41AI122431 · NIAID · VIRVIO, INC. · PI FULLER, DEBORAH H., KODAY, MERIKA TREANTS · 2016 to 2016
$209k
NIAID NIH HHS 1R41AI122431NIAID NIH HHS R01 AI091823NIAID NIH HHS R01 AI125704NIAID NIH HHS R21 AI119258NIAID NIH HHS R21 AI123920NIAID NIH HHS R33 AI119258NIAID NIH HHS R41 AI122431NIAID NIH HHS R56 AI117675NIAID NIH HHS R56 AI127371NIAID NIH HHS T32 AI007354NIGMS NIH HHS P41 GM103403NIH HHS S10 OD021527NINDS NIH HHS R01 NS080833
6 · The paper itself

Abstract

De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

Indexed as

Drug DesignBotulinum ToxinsComputer SimulationHemagglutinin Glycoproteins, Influenza VirusHot TemperatureHumansInfluenza, HumanMolecular Dynamics SimulationMolecular Targeted TherapyProtein BindingProtein EngineeringProteinsProtein StabilityTemperatureBotulinum ToxinsHemagglutinin Glycoproteins, Influenza VirusProteins

Identifiers

PMID28953867
PMCPMC5802399

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Registered trials

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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.