Perfecting proteins...  [Gaming for Science  - Foldit Game Site]    The first and arguably most influential research game was Foldit. Created by Zoran Popovic', a structural biologist and computer scientist at the University of Washington in Seattle, Foldit, launched in May 2008, challenges players to work out the three-dimensional structures of proteins by folding chains of virtual amino acids into optimal configurations. Results generated by online players have already accrued multiple publications in Nature journals since the game’s    The game grew out of Rosetta@Home, a project that farmed out computationally intensive protein-folding simulations to home computers. But rather than simply exploiting the spare processing power of PCs around the world, Foldit also makes use of the brainpower of computer owners by framing the problem as a competitive online game.    Players are presented with a hodgepodge of zigzags, squiggles, and loops representing the amino acids of a protein. Moving the cursor allows users to grab, bend, wiggle, and shake various parts of the molecule, with the aim of folding the messy structure into its optimal shape—the form that has the lowest energy—just as molecules tend to do in real life. The more stable the structure, the higher the score.    Foldit players quickly proved they could out perform the randomized runs of Rosetta, which simulates and tests millions of tweaks to the chain to find the shape with the lowest energy. In a challenge to work out the structures of 10 proteins that the scientists had already solved, the players got closer to the true structure than Rosetta for five of the proteins and matched it on three. Then, in September 2011, Foldit players made a breakthrough: they solved the structure of a retroviral protease of the Mason-Pfizer monkey virus, which causes an AIDS-like disease in monkeys—a problem that had stumped scientists for a decade. The study was published in Nature Structural and Molecular Biology (18:1175-77, 2011), listing the “Foldit Contenders Group” and the “Foldit Void Crushers Group” among its authors.  Foldit online protein folding gamers solve retroviral protease structure*
The game’s creators have also devised a way to extract and replicate Foldit players’ best folding strategies—which they were invited to encode and share as so-called “recipes”—in addition to their solutions. One such recipe, known as Blue Fuse, which evolved as it spread like wildfire among the game’s elite players, proved even more efficient than the algorithms that drive Rosetta (PNAS, doi:10.1073/pnas.1115898108, 2011). “It was really stunning,” says David Baker, a computational structural biologist at the University of Washington, who helped to create the game. “What they had developed, independently from us, was something better than the best current algorithm we were working on.”
In addition to deciphering and refining natural protein structures, the Foldit community is also trying its collective hand at designing better proteins. In January 2012, for example, Foldit players redesigned an enzyme in a way that sped up a reaction crucial to the production of a variety of drugs by almost 2,000 percent (Nature Biotechnology, 30:190-92, 2012). Researchers are also tasking Foldit players with designing and refining entirely new proteins, such as one to bind to and inhibit the influenza A virus, Baker says. “We’re trying to design potential protein therapeutics, and we’re enlisting Foldit players every step of the way.” Furthermore, Foldit’s designers hope to extend the drug discovery element of the game with a new toolbox of organic subcomponents that will enable the design of novel small molecules.
Foldit has helped to establish online games as a credible source of discovery in computational biology, says AndrewSu, Director of bioinformatics at Scripps Research Institute in La Jolla, CA. “The achievements of the Foldit player community are really eye-opening,” he says. “They’ve clearly hit on a model that is fun and scientifically productive. Now a lot of people are paying attention.”
from... TheScientist, by Staff,  Jan 2013, Playing Scientist, pg 42-48.