Stucture of AIDS-like virus enzyme solved in three weeks by online gamers
23 September 2011
The structure of a retrovirus enzyme whose configuration had
stumped scientists for more than a decade has been solved in three weeks
by gamers. The gamers achieved their discovery by playing Foldit, an
online game developed by the University of Washington that allows
players to collaborate and compete in predicting the structure of
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.
They did it in only three weeks.
This class of enzymes, called
retroviral proteases, has a critical role in how the AIDS virus
matures and proliferates. Intensive 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.
"We wanted to see if human intuition
could succeed where automated methods had failed," said Dr Firas
Khatib of the University of Washington Department of Biochemistry.
Khatib is a researcher in the protein structure lab of Dr David
Baker, professor of biochemistry.
Remarkably, the 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
A screenshot of the "Unsolved monkey virus
protein" Foldit puzzle, highlighting the Alignment Tool used by
Foldit players to combine regions from multiple models into a
single hybrid structure.
"These features provide exciting
opportunities for the design of retroviral drugs, including AIDS
drugs," wrote the authors of a paper appearing Sept. 18 in Nature
Structural & Molecular Biology. The scientists and gamers are
listed as co-authors.
This is the first instance that the
researchers are aware of in which gamers solved a longstanding
Fold-it was created by computer scientists at the University of
Washington Center for Game Science in collaboration with the Baker
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'
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.
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
"People have spatial reasoning
skills, something computers are not yet good at," Cooper said.
"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 Popovic, "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."
1. Khatib F et al. Crystal structure of a monomeric retroviral
protease solved by protein folding game players. Nature Structural
and Molecular Biology. Published online 18 September 2011;