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(Article by John Timmer)

"Foldit uses some of the same conventions typical of other computer games, like a few simple structural problems to give new users a smooth learning curve. It also borrows from other online gaming communities; there are leaderboards, team and individual challenges, user forums, and so on.

Though very few of those who played Foldit had any significant background in biochemistry, the gamers tended to beat Rosetta when it came to solving structures. In a series of ten challenges, they outperformed the algorithms on five and drew even on another three.

By tracing the actions of the best players, the authors were able to figure out how the humans' excellent pattern recognition abilities gave them an edge over the computer. For example, people were very good about detecting a hydrophobic amino acid when it stuck out from the protein's surface, instead of being buried internally, and they were willing to rearrange the structure's internals in order to tuck the offending amino acid back inside. Those sorts of extensive rearrangements were beyond Rosetta's abilities, since the energy changes involved in the transitions are so large.

Similarly, Rosetta was good at linking up stretches of protein through charge interactions and hydrogen bonds, but it would often get things slightly off (think of a zipper that's off by a single tooth). Shifting every bond by a single partner was beyond Rosetta's abilities, but it's something a human can do trivially.

That's not to say the Rosetta algorithm didn't play a valuable role in Foldit. Humans turn out to be really bad at starting from a simple linear chain of proteins; they need a rough idea of what the protein might look like before they can recognize patterns to optimize. Given a set of 10 potential structures produced by Rosetta, however, the best players were very adept at picking the one closest to the optimal configuration...

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