They're very good at that type of problem

With programming and game design provided by University of Washington computer scientists Seth Cooper (lead author of the Nature paper), Adrien Treuille (now at Carnegie Mellon University) and Zoran Popovic along with Firas Khatib and other researchers in Baker's group, Foldit debuted in May 2008 as an interactive extension of Rosetta, a computer program Baker developed to predict protein structures. Solving protein structures is one of the preeminent challenges in biology, requiring expensive, labor-intensive x-ray crystallography to divine the arrangement of the thousands of atoms that comprise each protein. Rosetta, in contrast, relies on a large scale search for the lowest energy shape of each protein – a computer-hungry process that requires trillions of calculations. Baker quickly realized that Rosetta was limited by the amount of supercomputer time he could secure. So in 2004 he developed a distributed version of Rosetta that individuals could load on their home or office computers to help perform some of Rosetta's calculations. Some 200,000 volunteers have downloaded and installed, which displays possible protein configurations as a screensaver. Foldit got its start when some of the users told Baker that they wished they had the ability to manipulate the proteins that their computers were helping to shape. "People saw that Rosetta was making obvious Rosetta Stone mistakes, and they were getting frustrated that they couldn't manipulate the proteins themselves," Baker says. Now that they can, some players have proven themselves better than Rosetta at certain tasks. In a "blind challenge" run last year, Foldit players competed directly with the Rosetta program in establishing the shapes of 10 proteins whose structures were, at the time, unknown. Humans outperformed Rosetta in five of the 10 trials, and performed just as well as Rosetta in three other trials. Baker says that humans are particularly good at seeing holes in a developing protein that need to be filled with dangling bits called side chains. "There's this class of problems where a residue should be sticking into the core of the protein but it isn't, it's sticking out," says Baker. "Rosetta moving that residue at random is not going to stick it into the core of the protein. But people can look at the protein, see that there's a hole, look at the side chain, see that it's sticking out, and put it in the right place. They're very good at that type of problem."After soliciting e-mail feedback from top players – some of whom devote six or more hours to each protein puzzle – Baker says he's overwhelmed by the sheer creativity displayed. "People wrote back these very, very sophisticated descriptions of algorithms they had come up with, how they had combined the tools we provided in very novel ways." Next up: Getting Foldit players to design proteins from scratch. Baker works with other scientists who are searching for new proteins that will act as drugs or contribute to environmentally-friendly projects such as making biofuels from carbon dioxide and sunlight. "Designing new proteins to fit a desired shape is something that Foldit players should be very good at," says Baker. While it may be years before a new crowd-sourced virtual protein helps solves a real-world problem, Baker is convinced that day will arrive. "

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