text-only page produced automatically by LIFT Text Transcoder Skip all navigation and go to page contentSkip top navigation and go to directorate navigationSkip top navigation and go to page navigation
National Science Foundation
News
design element
News
News From the Field
For the News Media
Special Reports
Research Overviews
NSF-Wide Investments
Speeches & Lectures
NSF Current Newsletter
Multimedia Gallery
News Archive
News by Research Area
Arctic & Antarctic
Astronomy & Space
Biology
Chemistry & Materials
Computing
Earth & Environment
Education
Engineering
Mathematics
Nanoscience
People & Society
Physics
 

Email this pagePrint this page


Press Release 11-197
On-line Gamers Succeed Where Scientists Fail, Opening Door to New AIDS Drug Design

Molecular structure of retrovirus enzyme solved through "Foldit"

Screenshot of the unsolved monkey virus protein Foldit puzzle.

The "unsolved monkey virus protein" Foldit puzzle, a tool used by online gamers.
Credit and Larger Version

September 19, 2011

Online gamers have solved the structure of a retrovirus enzyme whose configuration had stymied scientists.

The players were adept at a computer game, Foldit, that allows players to collaborate and compete in predicting the structure of protein molecules.

After scientists repeatedly failed to piece together the structure of a protein-cutting enzyme from an AIDS-like virus, they called in the Foldit players.

The scientists challenged the gamers to produce an accurate model of the enzyme.

This class of enzymes, called retroviral proteases, has a critical role in how the AIDS virus matures and proliferates.

Intensive research is underway 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 looked like.

"We wanted to see if human intuition could succeed where automated methods had failed," said biochemist Firas Khatib of the University of Washington (UW).

Remarkably, the gamers generated models good enough for the researchers to refine and determine the enzyme's structure within a few days.

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," write Khatib and co-authors of a paper appearing yesterday in the journal Nature Structural & Molecular Biology.

The scientists and gamers are all listed as co-authors.

"Online gamers have solved a longstanding scientific problem, perhaps leading the way to new anti-viral drugs," said Carter Kimsey, program director in the National Science Foundation's (NSF) Division of Biological Infrastructure, which funded the research.

"After this discovery, young people might not mind doing their online science homework," said Kimsey. "This is an innovative approach to getting humans and computer models to ‘learn from each other' in real-time."

Fold-it was created by computer scientists and biochemists at the UW Center for Game Science, and by paper co-author biochemist David Baker of UW, to engage the general public in scientific discovery.

The solution of the virus enzyme structure, the scientists said, indicates the power of online computer games to channel human intuition and of three-dimensional pattern-matching skills to solve challenging scientific problems.

With names like Foldit Contenders Group and Foldit Void Crushers Group, the gamers were excited about the task of real-world molecule-modeling problems.

The online protein folding game captivates thousands of avid players worldwide.

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.

Foldit is much more than a mind-boggling diversion.

As one player put it, the No. 1 reason to "crunch Rosetta at home and why you should, too, is a compelling mission: technology that could basically wipe out disease."

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.

Seth Cooper, a computer scientist at UW, is a co-creator of Foldit and its lead designer and developer, as well as a co-author of the paper. He studies human-computer exploration methods and the co-adaptation of games and players.

"People have spatial reasoning, something computers are not yet good at," Cooper said.

"Games provide a framework for bringing together the strengths of computers and humans. These results 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, Foldit used a new alignment tool for the first time to copy parts of known molecules and test their fit in an incomplete model.

"The ingenuity of game players," the paper concludes, "is a formidable force that, if properly directed, can be used to solve a wide range of scientific problems."

The other scientists involved in the project were Frank DiMaio, James Thompson and Zoran Popovic, director of the UW Center for Game Science; Macjiej Kazmierczyk, Miroslaw Gilski, Szymon Krsywda, Helena Zabranska, and Mariusz Jaskolski of the Faculty of Chemistry of A. Mickiewicz University in Poznan, Poland; and Iva Pichova of the Academy of Sciences of the Czech Republic, Prague.

The project was also supported by the UW Center for Game Science, the U.S. Defense Advanced Research Projects Agency (DARPA), the Howard Hughes Medical Institute, and the Microsoft Corporation.

-NSF-

Media Contacts
Cheryl Dybas, NSF, (703) 292-7734, cdybas@nsf.gov
Leila Gray, University of Washington, (206) 685-0381, leilag@u.washington.edu

The National Science Foundation (NSF) is an independent federal agency that supports fundamental research and education across all fields of science and engineering. In fiscal year (FY) 2014, its budget is $7.2 billion. NSF funds reach all 50 states through grants to nearly 2,000 colleges, universities and other institutions. Each year, NSF receives about 50,000 competitive requests for funding, and makes about 11,500 new funding awards. NSF also awards about $593 million in professional and service contracts yearly.

 Get News Updates by Email 

Useful NSF Web Sites:
NSF Home Page: http://www.nsf.gov
NSF News: http://www.nsf.gov/news/
For the News Media: http://www.nsf.gov/news/newsroom.jsp
Science and Engineering Statistics: http://www.nsf.gov/statistics/
Awards Searches: http://www.nsf.gov/awardsearch/

 

Screenshot of showing parts of protein structure that can be moved around by Foldit players.
Foldit players have control over which parts of proteins they'd like to move around.
Credit and Larger Version

Screen shot of a Foldit introductory level tutorial for hydrogen-bonding.
A Foldit introductory level tutorial for hydrogen-bonding; the player needs to move strands.
Credit and Larger Version

Screenshot of an active Foldit puzzle where leaderboard shows top score of each player/team.
A screenshot of an active Foldit puzzle. The leaderboard shows the top score of each player/team.
Credit and Larger Version

Screenshot showing how protein structure is reshaped by Foldit players.
Foldit players use a variety of tools to interactively reshape various regions of proteins.
Credit and Larger Version

Screenshot showing empty space, large red void, in a protein's center.
Foldit "freezing:" a large red void in a protein's center shows empty space.
Credit and Larger Version



Email this pagePrint this page
Back to Top of page