Evidence map›Paper›PMID 33398169›Full record

ArticleNature chemical biology2021

Bottom-up de novo design of functional proteins with complex structural features.

Che Yang, Fabian Sesterhenn, Jaume Bonet, Eva A van Aalen, Leo Scheller, Luciano A Abriata, Johannes T Cramer, Xiaolin Wen, Stéphane Rosset, Sandrine Georgeon and 5 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
11.5field-weighted citation impact, top 1% of its field
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

43 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
  2. Review
  3. Multimodal diffusion for joint design of protein sequence and structure.Protein science : a publication of the Protein Society · 2025
    Article
  4. A Complementarity-Based Approach to De Novo Binder Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Diversifying de novo TIM barrels by hallucination.Protein science : a publication of the Protein Society · 2024
    Article
  12. Review
  13. Article
  14. Article
  15. Computational Protein Design - Where it goes?Current medicinal chemistry · 2024
    Review
  16. Article
  17. Rational design of small-molecule responsive protein switches.Protein science : a publication of the Protein Society · 2023
    Review
  18. Article
  19. Article
  20. De novo protein design by inversion of the AlphaFold structure prediction network.Protein science : a publication of the Protein Society · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 4 countries.

Che Yang *Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-4591-5373
Fabian Sesterhenn *Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Jaume BonetInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0001-5210-4387
Eva A van AalenLaboratory of Chemical Biology and Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Leo SchellerInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0003-2490-4015
Luciano A AbriataInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0003-3087-8677
Johannes T CramerInstitute of Virology, Hannover Medical School, Hannover, Germany.ORCID http://orcid.org/0000-0002-2595-3188
Xiaolin WenDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Stéphane RossetInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Sandrine GeorgeonInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.ORCID http://orcid.org/0000-0002-8158-4508
Theodore JardetzkyDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3664-0072
Thomas KreyInstitute of Virology, Hannover Medical School, Hannover, Germany.
Martin FusseneggerDepartment of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.
Maarten MerkxLaboratory of Chemical Biology and Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.ORCID http://orcid.org/0000-0001-9484-3882
Bruno E CorreiaInstitute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. bruno.correia@epfl.ch.ORCID http://orcid.org/0000-0002-7377-8636
SIB Swiss Institute of Bioinformatics · CHEindhoven University of Technology · NLMedizinische Hochschule Hannover · DEStanford University · USETH Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

De novo protein design has enabled the creation of new protein structures. However, the design of functional proteins has proved challenging, in part due to the difficulty of transplanting structurally complex functional sites to available protein structures. Here, we used a bottom-up approach to build de novo proteins tailored to accommodate structurally complex functional motifs. We applied the bottom-up strategy to successfully design five folds for four distinct binding motifs, including a bifunctionalized protein with two motifs. Crystal structures confirmed the atomic-level accuracy of the computational designs. These de novo proteins were functional as components of biosensors to monitor antibody responses and as orthogonal ligands to modulate synthetic signaling receptors in engineered mammalian cells. Our work demonstrates the potential of bottom-up approaches to accommodate complex structural motifs, which will be essential to endow de novo proteins with elaborate biochemical functions, such as molecular recognition or catalysis.

Indexed as

Amino Acid MotifsBinding SitesCatalysisLigandsModels, MolecularProtein BindingProtein EngineeringProtein FoldingProteinsLigandsProteins

Identifiers

PMID33398169
OpenAlexW3120617366

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.