Foldit yields AIDS breakthrough

A project that turns protein folding into a competitive, online game has seen gamers do work in three weeks that had stumped scientists for over a decade
Written by Jack Clark, Contributor

Foldit, which makes protein folding into an immersive online game playable by the general public, has helped discover information with implications for the design of better AIDs drugs.

Foldit protein

Foldit allows gamers to help in scientific research by predicting and designing the structures of various proteins Photo credit: Foldit

The breakthrough, which was presented in a paper in Nature Structural & Molecular Biology (PDF) and announced by Foldit on Sunday, saw online gamers complete a challenge in three weeks that had puzzled scientists for over a decade.

"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 University of Washington wrote in a press release on Sunday. "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." 

Foldit gamers were able to create a protein model that was "good enough" for researchers to refine into a workable model, the University of Washington said. Foldit was created by the University of Washington's Centre for Game Science in collaboration with the Baker Lab in 2008.

"The critical role of Foldit players in the solution of the M-PMV PR structure shows the power of online games to channel human intuition and three-dimensional pattern-matching skills to solve challenging scientific problems," the researchers wrote in the paper. "Although much attention has recently been given to the potential of crowdsourcing and game playing, this is the first instance that we are aware of in which online gamers solved a longstanding scientific problem."

Role of proteins

Proteins are the fundamental workers of organic matter. They are made up of long chains of amino acids and underpin everything that goes on in the body — whether it's healing a cut, breaking down starch from food or sending signals within the brain, proteins do it. Their traits are dictated by the ordering of the amino acids in their chain and also their three-dimensional structure.

Scientists can easily analyse which amino acids make up a protein but the structure is much harder to work out. Foldit gives players a set of fundamental rules by which proteins can be arranged and gets them to do the hard work of trying out all the permutations into which the chains can be arranged until they hit upon the optimal one, which is the state that takes the lowest energy to maintain.

The ingenuity of game players is a formidable force that, if properly directed, can be used to solve a wide range of scientific problems.
–  Firas Khatib

Foldit presents players with a protein that they have to fold into its densest possible form while obeying certain physical rules: hydrophobics must be surrounded by as many atoms as possible to protect them from water; hydrophilics must be placed on the outside of the protein; and atoms must be packed carefully so they do not clash with one another.

Foldit's main goal is to gather data on how humans spatially manipulate proteins and feed the information through to automated computer programs to make them better. Another benefit is to present humans with problems that have proved intractable for scientists and computers and see if massed humanity can solve the problem, as in this case.

"The ingenuity of game players is a formidable force that, if properly directed, can be used to solve a wide range of scientific problems," Firas Khatib, a researcher in the protein structure lab of the University of Washington's department for biochemistry, said in a statement.

Foldit differs from other distributed computing schemes, such as Boinc, LHC@home 2.0, and Seti@Home, by relying on human interaction, rather than just using people's computers when they are otherwise idle.

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