Evidence mapPaperPMID 42056544Full record

ReviewNature2026

The past, present and future of de novo protein design.

Wei Yang, Shunzhi Wang, Gyu Rie Lee, Jason Z Zhang, Alexis Courbet, David Juergens, Xinru Wang, Thomas Schlichthaerle, Mohamad Abedi, Robert Ragotte and 14 more

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Amplicon/Protein Bead Display enables quantitativebioRxiv : the preprint server for biology · 2026
    Article
  3. Membrane-Associated Biomolecules for Synthetic Cell Signalling.Chembiochem : a European journal of chemical biology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
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

24 authors.

Wei Yang *Department of Biochemistry, University of Washington, Seattle, WA, USA.
Shunzhi Wang *Department of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-5033-7478
Gyu Rie Lee *Department of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-9119-5303
Jason Z Zhang *Department of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-0091-6273
Alexis CourbetDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-0539-7011
David JuergensDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-6425-8391
Xinru WangDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-5994-707X
Thomas SchlichthaerleDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-4444-2575
Mohamad AbediDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Robert RagotteDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Linna AnDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Indrek KalvetDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-6610-2857
Sam PellockDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7557-7985
Ljubica MihaljevicDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Cameron GlasscockDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-5223-6339
Arvind PillaiDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-5012-1199
Adam BroermanDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-6878-1769
Nathan EnnistDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-4823-9497
Ella HaefnerDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3837-6797
Nora McNamara-BordewickDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-4747-0627
Ian HaydonDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Lance StewartDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-4264-5125
Gaurav BhardwajInstitute for Protein Design, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-6554-2335
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA, USA. dabaker@uw.edu.ORCID http://orcid.org/0000-0001-7896-6217

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

With deep-learning-powered advances in protein design methods, there is an ongoing paradigm shift in protein engineering from random selection to intentional computational design methods. Here we describe the current state of de novo protein design. While there is still room for improvement in success rates and activities, the long-standing challenges of designing new protein structures, assemblies and protein binders are close to being solved. The key current questions in these areas are not how to design, but what to design, and open-source design methodology such as RFdiffusion and ProteinMPNN together with protein structure prediction tools enable biochemists and molecular biologists to broadly explore possible applications. There has also been considerable progress in the de novo design of small-molecule target binders, enzymes and multistate protein systems. Current challenges for methods development include design of catalysts for reactions with high energy barriers and, more generally, design of switches and nanomachines that integrate binding, conformational change and catalysis. Over the next five to ten years, we anticipate the design of sophisticated protein nanomachines and materials with functionality ranging far beyond that generated during natural evolution for a wide range of applications in medicine, technology and sustainability.

Indexed as

Protein EngineeringProteinsDeep LearningHistory, 21st CenturyHumansModels, MolecularProtein ConformationProteins

Identifiers

What Socratic 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 Socratic graph.