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The first several levels of Foldit are designed to teach players what good proteins look like and how to manipulate them using the tools of the game. Players can rotate proteins in three dimensions, pull together their constituent threads (called side chains), bend the protein’s overall structure (called the backbone), and try to generate hydrogen bonds, a stabilizing influence. The game graphically represents real protein chemistry. For example, it’s good to pack proteins tightly, but not too tightly: electrical charges in different regions of the side chains will repel each other if they’re too close to each other. Such clashes are represented by spiky, red burrs that disappear as the side chains are pulled apart.

After improving the designs of a few test proteins, players can advance into competitive play, working in teams or alone. Baker and Popović have set players to work on proteins whose structures are known in order to refine the game and train a group of players. In time, players will be working on new HIV vaccines and Baker’s other projects.

Luis von Ahn, a computer scientist at Carnegie Mellon University, agrees that humans bring problem-solving skills to the protein-folding game that computers can’t match. “The computer does a brute-force search, where we may know the shortcut,” he says. “We live in a 3-D world; we know how to navigate space.” Von Ahn has designed games that get people to help label images for Google and digitize books. Computers are bad at some tasks that are trivial for humans, such as recognizing a dog in a photograph or reading a blurry word. However, manipulating complex three-dimensional structures is a much tougher problem, and von Ahn worries that Foldit might be too difficult to gain a huge following.

Popović and Baker concede that the game is difficult. The aim is to make it entertaining enough that users will continue playing and get their friends to join in. By making the game available to anyone over the Web, the researchers expect to find people they call protein savants–people who are very good at solving protein structures and who will spend several hours a week playing the game.

Popović says that the designers will continue to improve Foldit by logging and analyzing what good and mediocre players do. “Through analyzing how people play, we’re learning what the best players are doing and improving the game play with that information,” he says. Dane Wittrup, a chemical engineer at MIT who designs proteins, says that this is a promising approach. “I suspect that if they carefully analyze successful game-playing strategies, they are likely to learn new, automatable strategies that they’ll incorporate into their structure prediction programs.”

Starting this afternoon, anyone can download the Foldit game for free.

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Credit: Foldit

Tagged: Biomedicine, 3-D, proteins, computer modeling, data visualization, online games

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