Playtime for proteins

In a new project, thousands of online gamers are helping scientists solve one of the body’s great mysteries
Jane Switzer

When Mark Thompson plays his favourite video game, he’s focused on fighting HIV and Alzheimer’s rather than killing aliens or battling zombies. Thompson is one of the top players on Foldit, an online game created by researchers at the University of Washington that uses the brainpower of gamers to figure out how proteins fold into their three-dimensional configurations. A library assistant by trade, he tried Foldit after a friend on a gaming forum recommended it a year ago. “For the first six months, I still didn’t know anything about it,” he says. “I just knew what looked right to me, and what looked wrong. I went with that, and it seemed to work.”

But according to University of Washington computer scientist Zoran Popovi´c, non-scientists with a love of problem solving, like Thompson, are exactly the kind of players Foldit needs. Proteins carry out almost all of the body’s important functions, and incorrectly folded proteins are linked to everything from allergies to Alzheimer’s disease. Knowing how the long chains of amino acids that make up proteins fold into a particular shape directly affects their function. And that process is still puzzling to scientists.

“If we knew that, we could probably have a path to eternal life,” Popovi´c says, noting the possibilities for specially designed vaccines and drugs. “But we’re nowhere close.”

With the help of Foldit’s dedicated players, however, they could be getting closer. Since Foldit became freely available online in 2008, thousands of lay people have signed up to become citizen scientists because they enjoy the Rubik’s Cube-like qualities of the game.  Now a researchers’ report, published last month in Nature, shows that Foldit players actually outperformed existing computer software designed to fold proteins.

Foldit begins with a series of tutorials designed to teach people about protein folding “without ever having to buy a chemistry book,” Popovi´c says. The game lets players tug, twist, reshape and build different proteins into more efficient structures. Structures become increasingly difficult, and a score is calculated based on packing proteins as small as possible, minimizing clashes between atoms and ensuring that hydrophobic molecules don’t touch water.
The idea came from Rosetta@home, a protein-folding program created in 2005 by University of Washington biochemistry professor David Baker, and run on the home PCs of hundreds of volunteers. The volunteers watched the program’s progress on their screen savers. When some of them began to notice mistakes in the process, Baker teamed up with Popovi´c to find a way to use their input.

Popovi´c notes that Foldit players come from every imaginable demographic, from teenagers to people in their 60s. When he and his research team submitted their findings to Nature, they made sure the 57,000 people who played Foldit over the last two years received due credit on the authors’ list, an unusual request that the editors originally denied. “I had to actually send them an impassioned plea that without them, the whole point of the paper is missed,” says Popovi´c.

Like Thompson, many Foldit players have no more than a high-school-level science education. “We brought complete novices to the point where they’re doing better than people with Ph.D.s in biochemistry,” Popovi´c says. He plans to establish a Center for Game Science at the university this fall to study the merits of science-oriented gaming.

For Thompson, 47, who can play for hours a day, the game is “a love-hate relationship.” He thinks Foldit loses players because it can be so frustrating. Still, he finds the thrill of making a small contribution addictive. “It’s real science,” he says. “You don’t feel like you’re playing a game.”