Researchers have developed a video game that rewards players for solving the scientifically substantial puzzles surrounding protein folding. The game, called Foldit, is the latest twist in the move toward the use of distributed computing and crowd-sourcing to solve huge scientific challenges.

Figuring out how complex molecules are bent and twisted could be key to developing new medicines and even nano-machines. Biochemists have found that the kinks in proteins act like stamped-out keys to unlock (or lock) the doors of cellular functions.

Misfolded proteins have been linked to a host of maladies, ranging from mad-cow disease to Alzheimer's disease and cystic fibrosis. In contrast, proteins that are folded just right could block the pathways used by the HIV virus and other cellular evildoers, or even open up new paths for making biofuels and cleaning up the environment.

Eventually, scientists would love to custom-design proteins for particular applications. But nature's rules for protein-folding are complex and varied. To simulate the chemical process, you need high-powered software, the patience to check thousands of permutations and the ability to manipulate virtual molecules with great precision.

Sounds like just the job for a gamer, right? That's exactly what the University of Washington's Seth Cooper and his colleagues thought.

In this week's issue of the journal Nature, they report that "top-ranked Foldit players excel at solving challenging structure refinement problems" in protein folding, even if they aren't scientists. They say their experience shows that interactive multiplayer games provide "a powerful new approach to solving computationally limited scientific problems."

The researchers incorporated 10 protein-folding puzzles into the game, and set up a scoring system that paralleled the way that molecules work. Structures could be swapped or re-twisted to increase scores, but if certain parts of the molecule got too close to each other, the players were penalized.

Cooper and his colleagues found that the gamers outperformed the protein-folding field's standard structure prediction software, known as Rosetta, on five of the 10 puzzles. On three of the puzzles, Foldit and Rosetta came up with similar results. On the other two puzzles, Rosetta's protein-structure predictions were numerically better but still "basically incorrect," the researchers said.

The researchers said the way gamers approached the puzzles was as interesting as the protein-folding predictions they eventually came up with.

"Foldit gameplay supports both competition and collaboration between players. For collaboration, players can share structures with their group members, and help each other out with strategies and tips through the game's chat function, or across the wiki. The competition and collaboration create a large social impact to the game, which alters the aggregate search progress of Foldit and heightens player motivation. As groups compete for higher rankings and discover new structures, other groups appear to be motivated to play more, and within groups the exchange of solutions can help other members catch up to the leaders."

All this may not sound surprising to folks who spend their nights and days fighting zombies in "Left 4 Dead," or building galactic empires in "Starcraft II." But for some researchers, this is an eye-opener. The result could well be that we'll see more human-plus-machine projects such as Foldit, Stardust @ Home, Galaxy Zoo and Moon Zoo.

Sounds like it's time for citizen scientists to level up. What do you think? Feel free to weigh in with your comments below.

In addition to Cooper, authors of "Predicting Protein Structures With a Multiplayer Online Game" include Firas Khatib, Janos Barbero, Michael Beenen, David Baker and Zoran Popovic of the University of Washington; Adrien Treuille and Jeehyung Lee of Carnegie Mellon University; Andrew Leaver-Fay of the University of North Carolina; and Foldit players. To learn more, check out this news feature from Nature.

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