EDGE on the Net

Gamers of the online game Fold.it have successfully modeled Mason-Pfizer monkey virus (M-PMV) retroviral protease, an enzyme that retroviruses like HIV need to reproduce.

Simply put, Fold.it allowed users to predict the shape of a protein and map it, using a game-like structure. The better the model, the more points they earned. In this case, scientists experimented with giving users just three weeks to create a model of a protein that scientists haven’t been able to model on a molecular level themselves -- despite 15 long years of trying.

At the end of the three-week period, scientists compared the best models to X-ray crystallography of the protein and what they discovered shocked them: At least one group of players had determined the correct structure, according to a report published by the University of Washington found in the journal Nature Structural & Molecular Biology.

Mapping the structure of protease is a key step toward developing new anti-viral medication therapies, but it eluded biochemists for more than a decade. In short, these gamers may not have Ph. D.’s but they’ve still managed to make an incredible scientific breakthrough.

Fold.it was launched in 2008 as a collaboration between the University of Washington’s computer science and biochemistry departments.

The university says it has two additional discoveries - one algorithmic, the other a brand-new protein - which it intends to publish in the near future. "It’s the power of citizen science," said Firas Khatib, a postdoctoral researcher in the laboratory of UW biochemistry professor David Baker.

Baker’s laboratory developed Fold.it about three years ago, believing that they could tap some of the brainpower that puzzle-loving humans pour into computer games.

"We wanted to see if human intuition could succeed where automated methods had failed," Khatib explained. "The ingenuity of game players is a formidable force that, if properly directed, can be used to solve a wide range of scientific problems."

Fold.it co-creator Seth Cooper added, "People have spatial reasoning skills, something computers are not yet good at. Games provide a framework for bringing together the strengths of computers and humans." The results show that gaming, science, and computation can be combined to make advances that were not possible before.

For the protease problem, Fold.it players started with scientists’ rough-draft ideas of the shape of protease based on a retrovirus that causes AIDS in monkeys. During three weeks of play, Fold.it players generated more than one million structure predictions.

The solution, reached by the winning team in only 10 days, was nearly perfect, researchers said. It gave Baker and his colleagues all the information they needed to nail down the structure almost to the last atom. "Competitive social interaction is a very strong driving force," Baker said.

Humans have an advantage, Khatib said, 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. Even the best computers and computer algorithms aren’t very good at that," he said.

The scientists offered co-authorship to players who supplied the winning answers but all declined, asking only for recognition for their teams - Contenders Group and 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 Fold.it username, mimi [sic].

However, the protein revelation is just one small part of the AIDS puzzle. It appears in the monkey version of AIDS, and plays a key role in the multiplication of the virus. With an accurate model of this protein, drugs can be created that could potentially help stymie the multiplication of the virus in humans.

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