A group of scientists who wanted help piecing together the structure of a protein-cutting enzyme from an AIDS-like virus challenged players of the online protein folding 'game' Foldit, created by computer scientists and the protein structure lab of biochemist Dr. David Baker at the University of Washington Center for Game Science. The science gamers 'solved' it in only three weeks.
This class of enzymes, called retroviral proteases, has a critical role in how the AIDS virus matures and proliferates. Research is under way to try to find anti-AIDS drugs that can block these enzymes but efforts were hampered by not knowing exactly what the retroviral protease molecule looks like.
The Foldit gamers generated models good enough for the researchers to refine and, within a few days, determine the enzyme's structure. Equally amazing, surfaces on the molecule stood out as likely targets for drugs to de-active the enzyme.
"These features provide exciting opportunities for the design of retroviral drugs, including AIDS drugs," wrote the authors of the paper in Nature Structural&Molecular Biology. The scientists and gamers are listed as co-authors. Dr. Firas Khatib of the University of Washington Department of Biochemistry led the study.
This is the first instance that the researchers are aware of in which gamers solved a longstanding scientific problem. Participation, along with Communication, Collaboration, and Publication, are the four cornerstones of our original Science 2.0 vision.
The solution of the virus enzyme structure, the researchers said, "indicates the power of online computer games to channel human intuition and three-dimensional pattern matching skills to solve challenging scientific problems."
With names like Foldit Contenders Group and Foldit Void Crushers Group, the gamer teams were fired up for the task of real-world molecule modeling problems. The online protein folding game captivates thousands of avid players worldwide and engages the general public in scientific discovery.
Players come from all walks of life. The game taps into their 3-D spatial abilities to rotate chains of amino acids in cyberspace. New players start at the basic level, "One Small Clash," proceed to "Swing it Around" and step ahead until reaching "Rubber Band Reversal."
Direct manipulation tools, as well as assistance from a computer program called Rosetta, encourage participants to configure graphics into a workable protein model. Teams send in their answers, and UW researchers constantly improve the design of the game and its puzzles by analyzing the players' problem-solving strategies.
Figuring out the shape and misshape of proteins contributes to research on causes of and cures for cancer, Alzheimer's, immune deficiencies and a host of other disorders, as well as to environmental work on biofuels.
The researchers noted that much attention has been given to the possibilities of crowd-sourcing and game playing in scientific discovery. Their results indicate the potential for integrating online video games into real-world science.
Dr. Seth Cooper, of the UW Department of Computing Science and Engineering, is a co-creator of Foldit and its lead designer and developer. He studies human-computer exploration methods and the co-evolution of games and players. "People have spatial reasoning skills, something computers are not yet good at. Games provide a framework for bringing together the strengths of computers and humans. The results in this week's paper show that gaming, science and computation can be combined to make advances that were not possible before."
Games like Foldit are evolving. To piece together the retrovirus enzyme structure, Cooper said, gamers used a new Alignment Tool for the first time to copy parts of know molecules and test their fit in an incomplete model.
"The ingenuity of game players," Khatib said, "is a formidable force that, if properly directed, can be used to solve a wide range of scientific problems.
According to director Dr. Zoran Popovic, associate professor of computer science and engineering, "Foldit shows that a game can turn novices into domain experts capable of producing first-class scientific discoveries. We are currently applying the same approach to change the way math and science are taught in school."
Citation: Firas Khatib, Frank DiMaio, Seth Cooper, Maciej Kazmierczyk, Miroslaw Gilski, Szymon Krzywda, Helena Zabranska, Iva Pichova, James Thompson, Zoran Popović, Mariusz Jaskolski& David Baker, 'Crystal structure of a monomeric retroviral protease solved by protein folding game players', Nature Structural&Molecular Biology doi:10.1038/nsmb.2119