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Accurate design of co-assembling multi-component protein nanomaterials

Nature volume 510, pages 103108 (05 June 2014) | Download Citation


The self-assembly of proteins into highly ordered nanoscale architectures is a hallmark of biological systems. The sophisticated functions of these molecular machines have inspired the development of methods to engineer self-assembling protein nanostructures; however, the design of multi-component protein nanomaterials with high accuracy remains an outstanding challenge. Here we report a computational method for designing protein nanomaterials in which multiple copies of two distinct subunits co-assemble into a specific architecture. We use the method to design five 24-subunit cage-like protein nanomaterials in two distinct symmetric architectures and experimentally demonstrate that their structures are in close agreement with the computational design models. The accuracy of the method and the number and variety of two-component materials that it makes accessible suggest a route to the construction of functional protein nanomaterials tailored to specific applications.

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Data deposits

The crystal structures and structure factors for the designed materials have been deposited in the RCSB Protein Data Bank ( under the accession codes 4NWN (T32-28), 4NWO (T33-15), 4NWP (T33-21, R32 crystal form), 4NWQ (T33-21, F4132 crystal form) and 4NWR (T33-28).


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We thank D. Shi and B. Nannenga (JFRC) for help with electron microscopy, F. DiMaio and R. Moretti for assistance with software development, P. Greisen for scripts used to compare side-chain conformations, J. Gallaher for technical assistance, M. Collazo for help with preliminary crystallization screening, D. Cascio and M. Sawaya for help with crystallographic experiments, and M. Capel, J. Schuermann and I. Kourinov at NE-CAT beamline 24-ID-C for help with data collection. This work was supported by the Howard Hughes Medical Institute (T.G. and D.B.) and the JFRC visitor program (S.G.), the National Science Foundation under CHE-1332907 (D.B. and T.O.Y.), grants from the International AIDS Vaccine Initiative, DTRA (N00024-10-D-6318/0024), AFOSR (FA950-12-10112) and DOE (DE-SC0005155) to D.B., an NIH Biotechnology Training Program award to D.E.M. (T32GM067555) and an NSF graduate research fellowship to J.B.B. (DGE-0718124). T.O.Y. and D.E.M. also acknowledge support from the BER programme of the DOE Office of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding bodies.

Author information

Author notes

    • Neil P. King
    • , Jacob B. Bale
    •  & William Sheffler

    These authors contributed equally to this work.


  1. Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA

    • Neil P. King
    • , Jacob B. Bale
    • , William Sheffler
    • , Shane Gonen
    •  & David Baker
  2. Institute for Protein Design, University of Washington, Seattle, Washington 98195, USA

    • Neil P. King
    •  & David Baker
  3. Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington 98195, USA

    • Jacob B. Bale
  4. UCLA Department of Chemistry and Biochemistry, Los Angeles, California 90095, USA

    • Dan E. McNamara
    •  & Todd O. Yeates
  5. Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA

    • Shane Gonen
    •  & Tamir Gonen
  6. UCLA-DOE Institute for Genomics and Proteomics, Los Angeles, California 90095, USA

    • Todd O. Yeates
  7. UCLA Molecular Biology Institute, Los Angeles, California 90095, USA

    • Todd O. Yeates
  8. Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA

    • David Baker


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N.P.K., J.B.B., W.S. and D.B. designed the research. N.P.K., J.B.B. and W.S. wrote program code and performed the docking and design calculations. N.P.K. and J.B.B. biophysically characterized the designed materials and prepared samples for structural analysis. S.G. characterized the designed materials by electron microscopy; S.G. and T.G. analysed electron microscopy data. D.E.M. crystallized the designed protein materials; D.E.M. and T.O.Y. analysed crystallographic data. N.P.K., J.B.B. and D.B. analysed data and wrote the manuscript. All authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David Baker.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Methods, Supplementary Tables 1-7 and Supplementary References.

Zip files

  1. 1.

    Design Models

    Zipped folder containing design models.

  2. 2.


    Zipped folder containing example files for docking protocol.

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    Zipped folder containing example files for design protocol.

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