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.
Department of Biochemistry, University of Washington, Seattle, Washington, USA.
James Thompson &
Department of Computer Science and Engineering, University of Washington, Seattle, Washington, USA.
Seth Cooper &
Department of Crystallography, Faculty of Chemistry, A. Mickiewicz University, Poznan, Poland.
Szymon Krzywda &
Center for Biocrystallographic Research, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.
Miroslaw Gilski &
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Helena Zabranska &
Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.
Foldit Contenders Group
Foldit Void Crushers Group
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.
Competing financial interests
The authors declare no competing financial interests.