Scientists were stumped.

For more than a decade, biochemists could not fully decipher the structure of a key protein, called a protease, that retroviruses such as HIV need to multiply. Knowing it would be a key step toward developing better anti-viral drugs.

So University of Washington scientists unleashed an avid group of online gamers. Within three furious weeks of play, pitting teams of non-scientists against each other, the gamers delivered the first accurate model of a retroviral protease.

"It's the power of citizen science," says Firas Khatib, a postdoctoral researcher in the laboratory of UW biochemistry professor David Baker. The UW

and

developed the game, called

, about three years ago, believing that they could tap some of the brain power that puzzle-loving humans pour into computer games.

There are many examples of crowdsourcing in science, but most involve citizens helping out with drudgery, such as submitting data on animal sightings or running distributed computing programs on a home computer. Foldit players are providing answers beyond the capabilities of experts in the field.

Solving protein structures remains one of the most difficult problems in science. Proteins take shape from a strand of building blocks, called amino acids. Genes tell a cell's protein-making machinery the order for assembling the building blocks in an orderly long strand. When a complex protein, such as an HIV protease, comes off the assembly line, it coils and folds to form an intricate molecular machine. Imagine, say, a sewing machine self-assembling from hundreds of parts arrayed on a string.

Because of the vast number of possible moves during protein folding, even the most advanced super computers still can't reliably predict the structure of large proteins. Foldit players use their intuition and three-dimensional problem-solving skills to figure out likely protein structures. Teams earn points by finding the most chemically stable shapes.

"Competitive social interaction is a very strong driving force," Baker says.

For the retrovirus problem, Foldit players started with scientists' rough-draft idea of the shape of the protease from a retrovirus that causes AIDS in monkeys. During three-weeks of play, gamers generated over one million structure predictions. The solution, reached by the winning team in 10 days, was nearly perfect; it gave Baker and colleagues all the information they needed to nail down the structure almost to the last atom. The journal

published the finding Sunday.

Human minds have an advantage, Khatib says, because of their intuitive ability to see the potential for a delayed payoff from moves that seem like backward steps.

"Human players can see that you may have to go down this road, not doing well for a long time, but those steps are necessary if you want to get to a more correct solution," he says. "Even the best computers and computer algorithms aren't very good at that."

The scientists offered co-authorship to players who supplied the winning answers but all declined, asking only for recognition for their teams: Foldit Contenders Group and Foldit Void Crushers Group.

"It is a team thing. Everybody contributes," said a player from the Contenders Group, who asked to be identified only by her Foldit user name, "mimi."

Baker and colleagues are posing even more difficult challenges to gamers. Among them: identifying the structures of compounds that could serve important medical needs, such as inhibiting flu viruses.

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