Foldit Gamers Solve Protein Folding Puzzle

in technology, medicine, biology, omics

According to a research report, following the failure to solve the crystal structure of a retroviral enzyme by conventional methods, Foldit game players were challenged to produce accurate models. Online gamers solved the structure of the retrovirus enzyme whose configuration had stymied scientists.

The enzyme is retroviral protease of Mason-Pfizer monkey virus (M-PMV).  The authors say that this class of enzymes, called retroviral proteases, has a critical role in how the AIDS virus matures and proliferates.

The scientists and gamers are all listed as co-authors.  The paper was published this week in Nature structural & molecular biology.

"We wanted to see if human intuition could succeed where automated methods had failed," said biochemist Firas Khatib of the University of Washington (UW).

Remarkably, the gamers generated models good enough for the researchers to refine and determine the enzyme's structure within a few days.

 Foldit game on protein folding 

Foldit "freezing:" a large red void in a protein's center
shows empty space. A screen shot. Credit: University of Washington

Equally amazing, surfaces on the molecule stood out as likely targets for drugs to de-active the enzyme.

"These features provide exciting opportunities for the design of retroviral drugs, including AIDS drugs," write Khatib and co-authors of the paper.

Fold-it was created by computer scientists and biochemists at the UW Center for Game Science, and by paper co-author biochemist David Baker of UW, to engage the general public in scientific discovery.

The solution of the virus enzyme structure, the scientists said, indicates the power of online computer games to channel human intuition and of three-dimensional pattern-matching skills to solve challenging scientific problems.

According to the University news releases, the online protein folding game captivates thousands of avid players worldwide. Players come from all walks of life. The game taps into their 3-D spatial abilities to rotate chains of amino acids in cyberspace.  New players start at the basic level, "One Small Clash," proceed to "Swing it Around," and step ahead until reaching "Rubber Band Reversal."  Direct manipulation tools, as well as assistance from a computer program called Rosetta, encourage participants to configure graphics into a workable protein model.

Teams send in their answers, and UW researchers constantly improve the design of the game and its puzzles by analyzing the players' problem-solving strategies.

Foldit is much more than a mind-boggling diversion.

Seth Cooper, a computer scientist at UW, is a co-creator of Foldit and its lead designer and developer, as well as a co-author of the paper. He studies human-computer exploration methods and the co-adaptation of games and players.

"People have spatial reasoning, something computers are not yet good at," Cooper said. "Games provide a framework for bringing together the strengths of computers and humans. These results show that gaming, science and computation can be combined to make advances that were not possible before."

"The ingenuity of game players," the paper concludes, "is a formidable force that, if properly directed, can be used to solve a wide range of scientific problems."

Source Article: Crystal structure of a monomeric retroviral protease solved by protein folding game players.  Firas Khatib, Frank DiMaio, Seth Cooper, Maciej Kazmierczyk, Miroslaw Gilski, Szymon Krzywda, Helena Zabranska, Iva Pichova, James Thompson, Zoran Popovi?, Mariusz Jaskolski & David Baker.   Nature Structural & Molecular Biology. Published online: 18 September 2011 | doi:10.1038/nsmb.2119

Additional source: University of Washington.
 

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