Evidence map›Paper›PMID 38194293›Full record

ArticleJournal of the American Chemical Society2024

Improving Protein Expression, Stability, and Function with ProteinMPNN.

Kiera H Sumida, Reyes Núñez-Franco, Indrek Kalvet, Samuel J Pellock, Basile I M Wicky, Lukas F Milles, Justas Dauparas, Jue Wang, Yakov Kipnis, Noel Jameson and 6 more

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.

0numbers the graph read from it
0cells of the map it votes in
142citing 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

142 citing papers in PubMed.

  1. Article
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  6. Towards routine accurate electron-density studies of biological macromolecules.Acta crystallographica. Section D, Structural biology · 2026
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  7. Review
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  15. Beyond native sequence recovery: Improved modeling of the sequence-energy landscape of protein structures.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

82 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

16 authors.

Kiera H SumidaDepartment of Chemistry, University of Washington, Seattle, Washington 98195, United States.ORCID 0000-0003-2773-9676
Reyes Núñez-FrancoCenter for Cooperative Research in Biosciences, Basque Research and Technology Alliance, Derio 48160, Spain.
Indrek KalvetInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.ORCID 0000-0002-6610-2857
Samuel J PellockInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Basile I M WickyInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.ORCID 0000-0002-2501-7875
Lukas F MillesInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Justas DauparasInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Jue WangInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Yakov KipnisInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Noel JamesonDepartment of Chemistry, University of Washington, Seattle, Washington 98195, United States.ORCID 0000-0001-9231-3765
Alex KangInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Joshmyn De La CruzInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Banumathi SankaranBerkeley Center for Structural Biology, Molecular Biophysics, and Integrated Bioimaging, Lawrence Berkeley Laboratory, Berkeley, California 94720, United States.
Asim K BeraInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Gonzalo Jiménez-OsésCenter for Cooperative Research in Biosciences, Basque Research and Technology Alliance, Derio 48160, Spain.ORCID 0000-0003-0105-4337
David BakerInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.

Funding

Spatial Organization in Biochemical Reaction NetworksR35GM124773 · NIGMS · UNIVERSITY OF WASHINGTON · PI Jesse George Zalatan · 2017 to 2026
$3.9M
De Novo Design of Minibinder Antagonists for COVID-19 and Future PandemicsR01AI160052 · NIAID · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID, FULLER, DEBORAH H. · 2021 to 2025
$3.5M
NIAID NIH HHS R01 AI160052NIGMS NIH HHS R35 GM124773
6 · The paper itself

Abstract

Natural proteins are highly optimized for function but are often difficult to produce at a scale suitable for biotechnological applications due to poor expression in heterologous systems, limited solubility, and sensitivity to temperature. Thus, a general method that improves the physical properties of native proteins while maintaining function could have wide utility for protein-based technologies. Here, we show that the deep neural network ProteinMPNN, together with evolutionary and structural information, provides a route to increasing protein expression, stability, and function. For both myoglobin and tobacco etch virus (TEV) protease, we generated designs with improved expression, elevated melting temperatures, and improved function. For TEV protease, we identified multiple designs with improved catalytic activity as compared to the parent sequence and previously reported TEV variants. Our approach should be broadly useful for improving the expression, stability, and function of biotechnologically important proteins.

Indexed as

EndopeptidasesRecombinant Fusion ProteinsTemperatureEndopeptidasesRecombinant Fusion Proteins

Identifiers

PMID38194293
PMCPMC10811672

What OpenQuestion holds

Textmetadata
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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.