Basic Science
Crystal structure of a monomeric retroviral protease solved by protein folding game players
Khatib F, Dimaio F, Cooper S, Kazmierczyk M, Gilski M, Krzywda S, Zabranska H, Pichova I, Thompson J, Popović Z, Jaskolski M, Baker D. Nat Struct Mol Biol. 2011 Sep 18. [Epub ahead of print]
Following the failure of a wide range of attempts to solve the crystal structure of M-PMV retroviral protease by molecular replacement, Khatib and colleagues 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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Editor’s note: Who would have thought that gamers would bring their human intuition and three-dimensional pattern-making skills to the table and solve a persistent molecular science challenge, ending up as co-authors on a scientific paper in the prestigious journal Nature Structural and Molecular Biology! With names like spvincent, grabhorn, and mimi, Foldit players from two teams, the Foldit Contenders and the Foldit Void Crushers, competed over a 3-week period to solve the crystal structure of a retroviral protease. This is an important objective: significant pharmaceutical attention is focused on developing antiretroviral drugs against these enzymes¾they are key to the maturation and multiplication of HIV. However, despite concerted efforts, this work has been hampered by complete failure over the past decade to determine the crystal structures of retroviral proteases. This first striking success opens the door to more integration of game-player ingenuity into scientific inquiry. This specific approach to on-line crowdsourcing could see on-line game players solving many more scientific problems – what a potentially great marriage of skills and challenges!
