Over a three-week period, online gamers playing Fold.it were able to decipher the structure of an enzyme of an AIDS-like virus. (The Mason-Pfizer monkey virus, M-PMV, retroviral protease causes an AIDS-like disease in monkeys.) One scientist says “they actually did it in less than 10 days” but researchers have been struggling with the problem for more than a decade.
From the Nature (subscription required) article which was published online Sunday, Crystal structure of a monomeric retroviral protease solved by protein folding game players (or download a PDF from the lead researcher):
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.
The solution required distributive collaboration, and the players — who spanned three continents are not biochemists:
Foldit players leverage human three-dimensional problem-solving skills to interact with protein structures using direct manipulation tools and algorithms… Players collaborate with teammates while competing with other players to obtain the highest-scoring (lowest-energy) models. In proof-of-concept tests, Foldit players—most of whom have little or no background in biochemistry—were able to solve protein structure refinement problems in which backbone rearrangement was necessary to correctly bury hydrophobic residues.
Computation biologist David Baker (the University of Washington*) developed Foldit “as an extension to his Rosetta@home program, which allows Baker to use home computers around the world to do complex calculations on protein structures.”
About 600 players from 41 teams submitted more than 1.25 million solutions. Narrowing those down to 5,000, [Mariusz Jaskolski of A. Mickiewicz University in Poland and the Polish Academy of Sciences] and colleagues subjected them to a computational technique called molecular replacement (MR), which tests the models against X-ray crystallography data. For MR to work, the proposed structure has to be very close to accurate, in which case the MR calculations can help perfect the details. But previous attempts at MR for this protein had failed because the protein models were too far off the mark.
But The Contender’s proposed protein structure was a winner. “When we took [their] model, it was a beautiful fit to the X-ray data so we knew [they] had solved it,” Baker said. “We were just totally blown away. This is the first time that a long-standing scientific problem has been solved by Foldit players, or to my knowledge, any scientific gaming participants.”
The final breakthrough came from Foldit user mimi, a member of The Contenders and a science technician at a high school near Manchester, UK, who has been playing Foldit for about 3 years. She “tucked in a flap” of the protein that was sticking out, she explains, to make the protein more “globular.” But she emphasizes that “the achievement was very much a group effort,” noting that it wasn’t possible for her to tuck in the flap until others in the group had made their key adjustments to the protein’s structure.
* Disclaimer: I teach at UW.
- Gamers Unlock Protein Mystery That Baffled AIDS Researchers For Years, PC World
- Gamers Solve Molecular Puzzle That Baffled Scientists, MSNBC
- Public Solves Protein Structure, The Scientist
- University of Washington Press Release