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Crystal structure of a monomeric retroviral protease solved by protein folding game players

Nature Structural & Molecular Biology volume 18, pages 1175–1177 (2011)Cite this article

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An Erratum to this article was published on 05 March 2012

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Abstract

Following the failure of a wide range of attempts to solve the crystal structure of M-PMV retroviral protease by molecular replacement, we challenged players of the protein folding game Foldit to produce accurate models of the protein. Remarkably, Foldit players were able to generate models of sufficient quality for successful molecular replacement and subsequent structure determination. The refined structure provides new insights for the design of antiretroviral drugs.

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Figure 1: Successful CASP9 predictions by the Foldit Void Crushers Group.
Figure 2: M-PMV retroviral protease structure improvement by the Foldit Contenders Group.
Figure 3: CPK representation of retropepsin surface.

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Protein Data Bank

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Protein Data Bank

Change history

  • 20 December 2011

    In the version of this article initially published, the location for the Academy of Sciences of the Czech Republic was given as Poznan. The Academy is in Prague. The error has been corrected in the HTML and PDF versions of the article.

References

  1. Rohl, C.A., Strauss, C.E., Misura, K.M. & Baker, D. Methods Enzymol. 383, 66–93 (2004).

    Article  CAS  Google Scholar 

  2. Cooper, S. et al. Nature 466, 756–760 (2010).

    Article  CAS  Google Scholar 

  3. Söding, J., Biegert, A. & Lupas, A.N. Nucleic Acids Res. 33, W244–W248 (2005).

    Article  Google Scholar 

  4. Kinch, L. et al. CASP9 assessment of free modeling target predictions. Proteins (in the press).

  5. MacCallum, J.L. et al. Assessment of protein structure refinement in CASP9. Proteins published online, doi:10.1002/prot.23131 (30 August 2011).

  6. Mastrolorenzo, A., Rusconi, S., Scozzafava, A., Barbaro, G. & Supuran, C.T. Curr. Med. Chem. 14, 2734–2748 (2007).

    Article  CAS  Google Scholar 

  7. Wlodawer, A. & Gustchina, A. Biochim. Biophys. Acta 1477, 16–34 (2000).

    Article  CAS  Google Scholar 

  8. Koh, Y. et al. J. Biol. Chem. 282, 28709–28720 (2007).

    Article  CAS  Google Scholar 

  9. Veverka, V. et al. J. Mol. Biol. 333, 771–780 (2003).

    Article  CAS  Google Scholar 

  10. DiMaio, F. et al. Nature 473, 540–543 (2011).

    Article  CAS  Google Scholar 

  11. McCoy, A.J. et al. J. Appl. Cryst. 40, 658–674 (2007).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the members of the Foldit team for their help designing and developing the game and all the Foldit players and Rosetta@home volunteers who have made this work possible. This work was supported by the Center for Game Science at the University of Washington, US Defense Advanced Research Projects Agency (DARPA) grant N00173-08-1-G025, the DARPA PDP program, US National Science Foundation grants IIS0811902 Work supported in part by grants 1M0508 and Z40550506 from the Czech Ministry of Education to I.P., the Howard Hughes Medical Institute (D.B.) and Microsoft Corp. This material is based upon work supported by the National Science Foundation under grant no. 0906026.

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Authors and Affiliations

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

    Firas Khatib, Frank DiMaio, James Thompson & David Baker

  2. Department of Computer Science and Engineering, University of Washington, Seattle, Washington, USA

    Seth Cooper & Zoran Popović

  3. Department of Crystallography, Faculty of Chemistry, A. Mickiewicz University, Poznan, Poland

    Maciej Kazmierczyk, Miroslaw Gilski, Szymon Krzywda & Mariusz Jaskolski

  4. Center for Biocrystallographic Research, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland

    Miroslaw Gilski & Mariusz Jaskolski

  5. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Helena Zabranska & Iva Pichova

  6. Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA

    David Baker

Authors
  1. Firas Khatib
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  2. Frank DiMaio
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  9. James Thompson
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  10. Zoran Popović
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Consortia

Foldit Contenders Group

Foldit Void Crushers Group

Contributions

F.K., F.D., S.C., J.T., Z.P. and D.B. contributed to the development and analysis of Foldit and to the writing of the manuscript; the F.C.G. and F.V.C.G. contributed through their gameplay, which generated the results for this manuscript; M.K. grew the crystals and collected X-ray diffraction data; M.G. processed X-ray data and analyzed the structure; S.K. refined the structure; H.Z. cloned, expressed and purified the protein; I.P. designed and coordinated the biochemical experiments, and contributed to writing the manuscript; M.J. coordinated the crystallographic study, analyzed the results and contributed to writing the manuscript.

Corresponding author

Correspondence to David Baker.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Discussion (PDF 997 kb)

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Khatib, F., DiMaio, F., Foldit Contenders Group. et al. Crystal structure of a monomeric retroviral protease solved by protein folding game players. Nat Struct Mol Biol 18, 1175–1177 (2011). https://doi.org/10.1038/nsmb.2119

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