Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

The Protein Design Archive (PDA): insights from 40 years of protein design

Nature Biotechnology volume 43, pages 669–671 (2025)Cite this article

Subjects

While natural proteins are incredibly diverse biomacromolecules, they present only a subset of the sequence and structural space that is chemically possible1. The field of protein design has the potential to illuminate the unexplored regions of this space, to deepen our understanding of sequence–structure–function relationships, and to enable the development of novel proteins that could be used to address societal challenges.

Protein design has evolved dramatically over the past 40 years from rational design to contemporary data-driven approaches. The field has now reached milestones such as the design of small-molecule2 and protein3 binders, entirely novel folds4,5,6, and has been recognized with a Nobel Prize. However, it can be difficult to identify current challenges and opportunities within the field as no easily searchable resource provides an overview of proteins that have been designed to date. Such a resource would improve our ability to learn from previous efforts and guide the development of future design methods.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Rapid increase in the number designed proteins that have been structurally characterized.
Fig. 2: Designed protein complexity compared to the PDB over time.

Data availability

The PDA is available without registration at https://pragmaticproteindesign.bio.ed.ac.uk/pda/. Source data are provided with this paper.

Code availability

Code supporting PDA data collection and processing is available on GitHub: https://github.com/wells-wood-research/chronowska-stam-wood-2024-protein-design-archive. This includes files detailing manual curation of the PDA dataset, such as csv files listing proteins that were manually included and excluded, and how information was manually corrected. Code used to build the PDA website is available on GitHub: https://github.com/wells-wood-research/protein-design-archive.

References

  1. Baker, D. Protein Sci. 28, 678–683 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lu, L. et al. Science 384, 106–112 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Gainza, P. et al. Nature 617, 176–184 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kuhlman, B. et al. Science 302, 1364–1368 (2003).

    Article  CAS  PubMed  Google Scholar 

  5. Thomson, A. R. et al. Science 346, 485–488 (2014).

    Article  CAS  PubMed  Google Scholar 

  6. Anishchenko, I. Nature 600, 547–552 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Burley, S. K. et al. Nucleic Acids Res. 49, D437–D451 (2021). (D1).

    Article  CAS  PubMed  Google Scholar 

  8. Leaver-Fay, A. et al. Methods Enzymol. 487, 545–574 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chaudhury, S., Lyskov, S. & Gray, J. J. Bioinformatics 26, 689–691 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Stam, M. J. & Wood, C. W. Protein Eng. Des. Sel. 34, gzab029 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Steinegger, M. & Söding, J. Nat. Biotechnol. 35, 1026–1028 (2017).

    Article  CAS  PubMed  Google Scholar 

  12. van Kempen, M. Nat. Biotechnol. 42, 243–246 (2024).

    Article  PubMed  Google Scholar 

  13. Huang, P.-S., Boyken, S. E. & Baker, D. Nature 537, 320–327 (2016).

    Article  CAS  PubMed  Google Scholar 

  14. Woolfson, D. N. J. Mol. Biol. 433, 167160 (2021).

    Article  CAS  PubMed  Google Scholar 

  15. Kortemme, T. Cell 187, 526–544 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the members of the Wells Wood Research Group for testing and feedback on the PDA website. M.C. is supported by a PhD studentship from the UK Research and Innovation-funded EastBio Doctoral Training Partnership programme. M.J.S., C.W.W. and D.N.W. are supported by a UKRI Biotechnology and Biological Sciences Research Council Strategic Longer and Larger award (BB/X003027/1).

Author information

Authors and Affiliations

  1. University of Edinburgh, School of Biological Sciences, Institute of Quantitative Biology, Biochemistry and Biotechnology, Edinburgh, UK

    Marta Chronowska, Michael J. Stam & Christopher W. Wood

  2. University of Bristol, Schools of Chemistry and of Biochemistry, Bristol BioDesign Institute, Max Planck-Bristol Centre, Bristol, UK

    Derek N. Woolfson

  3. Department of Agriculture, University of Napoli Federico II, Portici, Italy

    Luigi F. Di Costanzo

Authors
  1. Marta Chronowska
    View author publications

    Search author on:PubMed Google Scholar

  2. Michael J. Stam
    View author publications

    Search author on:PubMed Google Scholar

  3. Derek N. Woolfson
    View author publications

    Search author on:PubMed Google Scholar

  4. Luigi F. Di Costanzo
    View author publications

    Search author on:PubMed Google Scholar

  5. Christopher W. Wood
    View author publications

    Search author on:PubMed Google Scholar

Contributions

M.C. and C.W.W. created the website, with support from M.J.S. M.C. and L.F.D.C. collected the data. M.C. and M.J.S. processed and analyzed the data. C.W.W. and D.N.W. conceived the project and secured the funding. M.C. with support of M.J.S. and C.W.W. prepared the manuscript; D.N.W. and L.F.D.C. edited the manuscript.

Corresponding authors

Correspondence to Luigi F. Di Costanzo or Christopher W. Wood.

Ethics declarations

Competing interests

The authors declare no competing interests.

Supplementary information

Supplementary Information

Supplementary Figs. 1–4, Tables 1–4, Discussion, Methods, Software Versions, Front-end Requirements, Back-end Requirements, References

Source data

Source Data Fig. 1

The Protein Design Archive dataset as of 1 January 2025

Source Data Fig. 2

Structure-based metrics generated with DE-STRESS for proteins found in the Protein Design Archive database as of 1 August 2024 and the Research Collaboratory for Structural Bioinformatics Protein Data Bank as of 1 June 2024

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chronowska, M., Stam, M.J., Woolfson, D.N. et al. The Protein Design Archive (PDA): insights from 40 years of protein design. Nat Biotechnol 43, 669–671 (2025). https://doi.org/10.1038/s41587-025-02607-x

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41587-025-02607-x

This article is cited by

Search

Advanced search

Quick links

Nature Briefing AI and Robotics

Sign up for the Nature Briefing: AI and Robotics newsletter — what matters in AI and robotics research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: AI and Robotics