Since October, 2000 the Folding@home project has been used to understand protein folding. Scientists know the pieces that make up a protein but cannot predict how those parts fit together into a 3-D structure. So the Folding@home project harnesses the power of Internet-connected PC’s and consoles, such as the PS3, to form the most powerful distributed computing cluster in the world. But no computer in the world is big enough, and computers may not take the smartest approach. So a team from the University of Washington (UW) made a Tetris-like game that asks players to fold a protein rather than stack colored blocks and discovered that people can compete with supercomputers in this arena.

The game, Foldit, turns protein-folding into a game and awards points based on the internal energy of the 3-D protein structure, dictated by the laws of physics. Thousands of people have now played the game and results published in the journal Nature show that Foldit is a success. Analysis showed that players bested the computers on problems that required radical moves, risks and long-term vision – the kinds of qualities that computers do not possess.

"People in the scientific community have known about Foldit for a while, and everybody thought it was a great idea, but the really fundamental question in most scientists' minds was 'What can it produce in terms of results? Is there any evidence that it's doing something useful?'" said principal investigator Zoran Popović, a UW associate professor of computer science and engineering.

"I hope this paper will convince a lot of those people who were sitting on the sidelines, and the whole genre of scientific discovery games will really take off," he said.

Making science fun

A major challenge in developing the game was to make it fun while still producing valid scientific results, said Seth Cooper, a UW doctoral student in computer science. There was a constant back-and-forth between scientists, game developers and players to achieve the best balance.

The class of problems in which humans were able to do better than computers required intuitive leaps or major shifts in strategy. Future work will aim to better combine the strengths of experts, computers and thousands of game players.

"It's a new kind of collective intelligence, as opposed to individual intelligence, that we want to study," Popović said. "We're opening eyes in terms of how people think about human intelligence and group intelligence, and what the possibilities are when you get huge numbers of people together to solve a very hard problem.”

The Foldit energy calculations are carried out by Rosetta, the procedure for computing protein structures developed by co-author David Baker, a UW biochemistry professor. Baker's group has previously used donated computer cycles through Rosetta@home to help crunch through the trillions of possible orientations for the chains of amino acid molecules that make up proteins.

The human thinking patterns may now help bolster Rosetta's skills. Researchers in Baker's group are analyzing the most successful Foldit strategies and trying to replicate them in the computer-powered version.

Foldit’s focus

This summer the Foldit community has been focused on problems in the Critical Assessment of Techniques for Protein Structure Prediction competition, the world's largest comparison of protein-folding computation strategies. Last year Foldit competed as part of the Baker lab team. This year for the first time Foldit players have their own team, taking on the most sophisticated supercomputers in the world. Contest results will be announced in December.

Now, Foldit players will focus on designing novel proteins. Last year a Texas player who goes by the name "BootsMcGraw" was the first Foldit player to have his new protein design synthesized in the Baker lab. Although this particular structure did not work, the researchers plan to try again and are optimistic about the possibilities.

"I think that design problems are an area where human computing has huge potential," Baker said. "People are good at building things, so I'm expecting that people will be very good at building proteins for different purposes. That's where I'm expecting really great things from Foldit.”

The UW researchers say that players may someday design proteins to disable the flu virus or tackle HIV, or perform tasks outside the body such as cleaning up waste or generating energy.

"We're taking the effort that people put into games and channeling that into something productive and useful for humanity," Cooper said. "We're combining computational power and human brainpower to tackle important problems that neither one of them can do alone.”

Anyone interested in adding their gray matter to the cause can visit the Foldit blog where they can download the game and find out about updates to the game, upcoming competitions, and special events like online chats with the scientists or game developers.