Story:
Foldit: Citizen Scientists "thinking together" to find a cure for cancer

Rosetta@home
David Baker’s lab developed software that virtually folds protein sequences into thousands of possible shapes, based on “rules” that are summarized in the program and termed the “Rosetta score.” The conformations that most closely resemble the actual shape of the protein earned the lowest score. The program allowed users to watch the computer methodically tugging and twisting the protein on their screensavers, if they wished. When Rosetta@home was launched in 2005, thousands of people signed up.

 An unexpected opportunity
The volunteers were really watching those screensavers, and some were frustrated at the slow pace of progress. They began writing in with suggestions for better conformations. Baker was startled, but it made sense. When it comes to protein folding, humans have a distinct advantage over computers: a highly evolved talent for spatial reasoning, or literally seeing solutions. We also have intuition and are adaptive, which makes us better at “intelligent guessing” and recognizing a dead end early, especially with experience. Baker immediately put together a team of computer scientists to figure out how to meld man and machine in protein folding, with Seth Cooper taking on the role of lead designer and co-creator.

 Designing Foldit
The team wanted to give users both the tools and incentive to participate in what essentially is puzzle solving.  So they decided to go beyond building an interface for assisting in the computation, and to develop an online game. Foldit presents protein folding as a visual or spatial challenge; the goal is to arrange an on-screen protein into the smallest possible shape, within game rule parameters. Developers knew it would be critical to keep volunteers’ interest, so that they’d quickly learn the skills needed to be able to make a meaningful contribution.

Designers weren’t expecting people to know anything about biology to play—and with the right tools and some training, they shouldn’t have to. For new players, there is a 40-minute introductory video, and a series of tutorial puzzles that familiarize them with the game’s interface, rules and solving aids. After that, they can play any of the puzzles posted on the Foldit site, some of which are beginner level. In the game, players have a set of controls that let them manipulate (e.g., “shake,” “wiggle,” “rebuild”) a protein into a more tightly packed, efficient structure.

Designers wanted to give Foldit players the tools to collaborate and self-organize too. Users can play puzzles individually or join groups, many of which are open to anyone. They can read and contribute to a wiki, and join in on a chat room. More experienced players are invited to help out newcomers. And to harness the gaming spirit of competitiveness, there are increasingly difficult levels of play, from beginner on up. As a protein is restructured, a score is calculated based on how well it is folded and displayed on screen. Players strive to get high scores on each puzzle, and make it to the top of overall player rankings.

 Foldit experience
More than 57,000 people have played the game since Foldit’s launch in May 2008. Baker has been so impressed with players’ skills that they’re now encouraged to go beyond folding to do actual protein design. On a more academic level, his team has been studying whether humans’ pattern recognition and puzzle-solving abilities make us more efficient than existing computers at protein folding. In five of ten blind challenges – puzzles involving protein structures known to us but not publicly available – the best Foldit result was substantially better than that of a superfast computer. In three, they were equally close to the final shape. In the two most difficult puzzles, neither was very close.