Gamers take up protein folding

Source: University of Washington

Gamers have devoted countless years of collective brainpower to rescuing princesses or protecting the planet against alien invasions. Now researchers at the University of Washington in the US are trying to harness those finely honed skills to make medical discoveries, perhaps even finding a cure for HIV.

A new game called Foldit turns protein folding into a competitive sport. Introductory levels teach the rules, which are the same laws of physics by which protein strands curl and twist into three-dimensional shapes - key for biological mysteries ranging from Alzheimer's to vaccines.

After about 20 minutes of training, people feel like they're playing a video game but are actually mouse-clicking in the name of medical science.

The game was developed by doctoral student Seth Cooper and postdoctoral researcher Adrien Treuille, both in computer science and engineering, working with Zoran Popovic, a UW associate professor of computer science and engineering; David Baker, a UW professor of biochemistry and Howard Hughes Medical Institute investigator; and David Salesin, a UW professor of computer science and engineering. Professional game designers provided advice during the game's creation.

"We're hopefully going to change the way science is done, and who it's done by," Popovic said. "Our ultimate goal is to have ordinary people play the game and eventually be candidates for winning the Nobel Prize."

Computer simulators calculate all possible protein shapes, but this is a mathematical problem so huge that all the computers in the world would take centuries to solve it. In 2005, Baker developed a project named Rosetta@home that taps into volunteers' computer time all around the world. But even 200,000 volunteers aren't enough.

"There are too many possibilities for the computer to go through every possible one," Baker said. "An approach like Rosetta@home does well on small proteins, but as the protein gets bigger and bigger it gets harder and harder, and the computers often fail.

"People, using their intuition, might be able to home in on the right answer much more quickly."

Rosetta@home and Foldit both use the Rosetta protein-folding software. Foldit is the first protein-folding project that asks volunteers for something other than unused processor cycles on their computers or Playstation machines. Foldit also differs from recent human-computer interactive games that use humans' ability to recognise images or interpret text. Instead, Foldit capitalises on people's natural 3D problem-solving skills.

The intuitive skills that make someone good at playing Foldit are not necessarily the ones that make a top biologist. Baker says his 13-year-old son is faster at folding proteins than he is. Others may be even faster.

"I imagine that there's a 12-year-old in Indonesia who can see all this in their head," he said.

The game looks like a 21st-century version of Tetris, with multicolored geometric snakes filling the screen. A team that includes a half-dozen UW graduate and undergraduate students spent more than a year figuring out how to make the game both accurate and engaging. They faced some special challenges that commercial game developers don't encounter.

"We don't know what the best result is, so we can't help people or hint people toward that goal," Popovic said. The team also couldn't arbitrarily decide to make one move worth 1,000 bonus points, since the score corresponds to the energy needed to hold the protein in that shape.

Almost 1,000 players have tested the system in recent weeks, playing informal challenges using proteins with known shapes. Starting this week, however, the developers will open the game to the public and offer proteins of unknown shapes. Also starting this week, Foldit gamers will face off against research groups around the world in a major protein-structure competition held every two years.

Foldit includes elements of multiplayer games in which people can team up, chat with other players and create online profiles. Over time the researchers will analyse people's moves to see how the top players solve puzzles. This information will be fed back into the game's design so the game's tools and format can evolve.

The research is funded by the US Defense Advanced Research Projects Agency, the Howard Hughes Medical Institute, Microsoft and Adobe, and through fellowships at Nvidia and Intel.