Gamers whip up their own scientific 'recipes'

UW Center for Game Science / Baker Lab

Foldit players learn to resolve structural conflicts in a protein molecule due to amino acid size (indicated by spiky red balls in this game visualization).

By Alan Boyle

Researchers?say that players of a protein-folding game called Foldit are coming up with molecular "recipes" that rival their own complex algorithms.

One of the recipes ? a computerized tool called "Blue Fuse," which checks whether a protein molecule is in its highest-scoring?configuration ??knocked Foldit's creators for a loop. "When I saw the Blue Fuse algorithm, I recognized immediately that it was almost identical in concept to the best algorithm that we developed in my research group over a period of years," David Baker, a?biochemist at the University of Washington, told me today.

It took the players of the Foldit game only?about seven months to come up with their version, and they're continuing to improve the recipe.

"We were shocked to find state-of the art algorithms," Zoran Popovic, director of UW's Center for Game Science and the game's co-creator, said in a university news release.

UW?computer scientist Seth Cooper,?Foldit's other co-creator as well as lead designer/developer, said the findings demonstrate the power of collaborative game play for solving scientific problems. "It's a great thing to show what kinds of things video games and gamers can accomplish," he told me.

The science behind the recipe-writing process is detailed in a research paper published online this week in the Proceedings of the National Academy of Sciences.

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More than a game
Protein-folding isn't just a game: The structures of protein molecules are the keys to a wide range of biological processes. In a sense, proteins literally serve as "keys" and "locks" to open up cellular pathways, to admit or block viruses, to start or stop the machinery of life.?If scientists can gain a better understanding of how those keys and locks work, they could actually design their own molecules for future medications and nanomachines.

That's where Foldit and other protein-folding software tools can play a huge role. Foldit is a social game based on a computerized molecule-manipulation program called Rosetta, which was developed a decade ago?by Baker and his colleagues at UW. The Foldit game?has enlisted hundreds of thousands of players who can work together (or compete against each other) to twist and turn virtual molecules and rack up high scores. The scores are based on how?well players can fold molecules to produce the lowest-energy?state ? the state?that is preferred in nature.

Just a couple of months ago, UW?researchers credited Foldit players?with?figuring out?the right structure for an?enzyme from an AIDS-like virus found in rhesus monkeys. The latest research focuses on the processes used by the players rather than the results.

Players trade recipes
Starting in mid-2009, Foldit's developers made it possible for players to create and share?their own algorithms for manipulating molecules automatically. The gamers?refer to?these software routines as "recipes."

"A lot of them have been shared with their own teammates, of course, and also with the players that they're competing against," UW biochemist Firas Khatib, a co-author for the paper, told me. "In some of the descriptions, they say, 'You might want to put the kettle on for this one,' or 'You might want to let this one run for a few days.'"

Over the months that followed, Foldit players tinkered with the recipes to produce tastier molecules with less time and effort.

"The whole thing was a social process," Cooper explained. "It's really drawing on the collective intelligence of the Foldit players as?a whole, to come up with the algorithms and also decide which ones are useful."

Blue Fuse became one of the most popular recipes among the gamers. Khatib said the software tool takes the code for a molecule folded in a particular way, and bends the rules of the game temporarily to check whether there's an even better solution to the puzzle. If there is, the software back-tracks through previous moves and heads for that better solution instead. "That's literally how simple the algorithm is, which is why it's so brilliant," Khatib said.

Researchers conduct cook-off
It turned out that Blue Fuse was similar to an algorithm in the more sophisticated Rosetta program, known as Fast Relax. That algorithm was a new, improved (but unpublished) version of an older software tool called Classic Relax. The researchers staged a recipe cook-off to see how the three algorithms compared. Blue Fuse took less time to come up with a low-energy solution to a given protein puzzle than Classic Relax, but more time than the improved Fast Relax.

That wasn't the end of the cook-off, however. "One of the reviewers for our paper pointed out that that's a completely unfair competition," Khatib said.

The reviewer observed that?Fast Relax was taking advantage of software routines in Rosetta?that were not available in Foldit. When the UW researchers adapted Fast Relax for the Foldit program, they found that?Blue Fuse identified low-energy puzzle solutions faster ? although Fast Relax could find even?lower-energy solutions if it was allowed to run for more than 200 seconds of CPU time. (The average Blue Fuse runtime during gameplay was 122 seconds.)

"For 200 seconds and less, Blue Fuse is actually better than Fast Relax," Khatib said. "It optimizes faster."

Baker said the next step is to give the gamers more power. "What we're doing now is taking many more of the Rosetta options and parameters and exposing them to Foldit players, so that they can use them. ... I'm really excited to see what Foldit players can do once they have access to the full palette of options," he told me.

He said it won't be all that long before the Foldit players are recruited not only to solve protein-folding puzzles, but also to try out molecular designs that could lead to "new virus inhibitors, new carbon-fixation pathways, new routes to vaccines."

"We're now learning enough of the rules that we can actually make our own proteins," Baker said.

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In addition to Khatib, Cooper, Popovic and Baker, co-authors of "Algorithm Discovery by Protein Folding Game Players" include Michael Tyka, Kefan Xu, Ilya Makedon and Foldit players. ?The Foldit project was developed by the UW Center for Game Science in collaboration with?UW's Baker Laboratory, with funding from the Defense Advanced Research Projects Agency, the National Science Foundation, the Howard Hughes Medical Institute, Adobe and Microsoft Corp. (Microsoft and NBC Universal are partners in the msnbc.com joint venture.)

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Source: http://cosmiclog.msnbc.msn.com/

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