Gamers solve complex scientific problem in 3 weeks
Crystal structure of a monomeric retroviral protease solved by protein folding game players
Firas Khatib,1 Frank DiMaio,1 Foldit Contenders Group, Foldit Void Crushers Group, Seth Cooper,2 Maciej Kazmierczyk,3 Miroslaw Gilski,3, 4 Szymon Krzywda,3 Helena Zabranska,5 Iva Pichova,5 James Thompson,1 Zoran Popović,2 Mariusz Jaskolski3, 4 & David Baker1, 6
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.Foldit is a multiplayer online game that enlists players worldwide to solve difficult protein-structure prediction problems. Foldit players leverage human three-dimensional problem-solving skills to interact with protein structures using direct manipulation tools and algorithms from the Rosetta structure prediction methodology1. Players collaborate with teammates while competing with other players to obtain the highest-scoring (lowest-energy) models. In proof-of-concept tests, Foldit players—most of whom have little or no background in biochemistry—were able to solve protein structure refinement problems in which backbone rearrangement was necessary to correctly bury hydrophobic residues2. Here we report Foldit player successes in real-world modeling problems with more complex deviations from native structures, leading to the solution of a long-standing protein crystal structure problem.
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Journal name: Nature Structural & Molecular Biology
- Volume: 18,
- Pages: 1175–1177
- Year published: (2011)
- DOI: doi:10.1038/nsmb.2119
- Received
- Accepted
- Published online
