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

An Erratum to this article was published on 05 March 2012

This article has been updated

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.

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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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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.

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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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