Evidence map›Paper›PMID 27626386›Full record

ArticleNature2016

Accurate de novo design of hyperstable constrained peptides.

Gaurav Bhardwaj, Vikram Khipple Mulligan, Christopher D Bahl, Jason M Gilmore, Peta J Harvey, Olivier Cheneval, Garry W Buchko, Surya V S R K Pulavarti, Quentin Kaas, Alexander Eletsky and 17 more

Abstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers.

0numbers the graph read from it
0cells of the map it votes in
209citing 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

209 citing papers in PubMed.

  1. Article
  2. A scalable recombinant pipeline for disulphide-stapled peptides.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Mapping targetable sites on the human surfaceome for the design of novel binders.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  12. CyclicMPNN: Stable Cyclic Peptide Sequence Generation.bioRxiv : the preprint server for biology · 2026
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Buttressing ligand-binding pockets in de novo designed NTF2-like domains.Protein science : a publication of the Protein Society · 2025
    Article
  20. Review

149 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

27 authors.

Gaurav BhardwajDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Vikram Khipple MulliganDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Christopher D BahlDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Jason M GilmoreDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Peta J HarveyInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Olivier ChenevalInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Garry W BuchkoSeattle Structural Genomics Center for Infectious Diseases, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
Surya V S R K PulavartiDepartment of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260, USA.
Quentin KaasInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Alexander EletskyDepartment of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260, USA.
Po-Ssu HuangDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
William A JohnsenClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Per Jr GreisenDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Gabriel J RocklinDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Yifan SongDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Thomas W LinskyDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
Andrew WatkinsDepartment of Chemistry, New York University, New York, New York 10003, USA.
Stephen A RettieInstitute for Protein Design, University of Washington, Seattle, Washington 98195, USA.
Xianzhong XuDepartment of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260, USA.
Lauren P CarterInstitute for Protein Design, University of Washington, Seattle, Washington 98195, USA.
Richard BonneauDepartment of Biology, New York University, New York, New York 10003, USA.
James M OlsonClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Evangelos CoutsiasApplied Mathematics and Statistics and Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, New York 11794, USA.
Colin E CorrentiClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Thomas SzyperskiDepartment of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260, USA.
David J CraikInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
David BakerDepartment of Biochemistry, University of Washington, Seattle, Washington 98195, USA.

Funding

THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI JAYADEY, SUMAN · 1985 to 2019
$57.2M
University of Georgia ProjectU54GM094597 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI KENNEDY, MICHAEL ALLEN · 2010 to 2014
$36.9M
New Mathematical Methods for Protein Loop ModelingR01GM090205 · NIGMS · UNIVERSITY OF NEW MEXICO · PI COUTSIAS, EVANGELOS A. · 2009 to 2012
$1.3M
Howard Hughes Medical InstituteNIAID NIH HHS HHSN272201200025CNIA NIH HHS P50 AG005136NIGMS NIH HHS R01 GM090205NIGMS NIH HHS U54 GM094597
6 · The paper itself

Abstract

Naturally occurring, pharmacologically active peptides constrained with covalent crosslinks generally have shapes that have evolved to fit precisely into binding pockets on their targets. Such peptides can have excellent pharmaceutical properties, combining the stability and tissue penetration of small-molecule drugs with the specificity of much larger protein therapeutics. The ability to design constrained peptides with precisely specified tertiary structures would enable the design of shape-complementary inhibitors of arbitrary targets. Here we describe the development of computational methods for accurate de novo design of conformationally restricted peptides, and the use of these methods to design 18-47 residue, disulfide-crosslinked peptides, a subset of which are heterochiral and/or N-C backbone-cyclized. Both genetically encodable and non-canonical peptides are exceptionally stable to thermal and chemical denaturation, and 12 experimentally determined X-ray and NMR structures are nearly identical to the computational design models. The computational design methods and stable scaffolds presented here provide the basis for development of a new generation of peptide-based drugs.

Indexed as

Computer-Aided DesignDrug DesignProtein StabilityAmino Acid MotifsCrystallography, X-RayCyclizationDisulfidesHot TemperatureModels, MolecularNuclear Magnetic Resonance, BiomolecularPeptidesPeptides, CyclicProtein DenaturationProtein Structure, SecondaryProtein Structure, TertiaryStereoisomerismDisulfidesPeptidesPeptides, Cyclic

Identifiers

PMID27626386
PMCPMC5161715

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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.