Researchers at the University of Washington were stumped. They were looking at a protein that causes AIDS in rhesus monkeys, but after 14 years of study, no one was able to figure out the protein's exact structure.
Researcher Firas Khatib tells Rachel Martin, host of weekends on All Things Considered, that even the most advanced imaging techniques couldn't capture this little particle.
"The reason that the problem is so hard is that proteins are so small you can't see them with a microscope," he says.
Also, a protein can fold up into so many possible shapes that a computer can't run through them all.
But when scientists failed, gamers came to the rescue.
Seth Cooper, creative director of the university's Center for Game Science, had invented a computer game called Foldit, in which players compete against one another to design the most accurately folded proteins.
"There are all these little pieces and atoms that need to fit together in just the right way for the protein to fold," Cooper says. "It's a lot like a 3-D jigsaw puzzle, or kind of like a 3-D Tetris."
Cooper describes proteins as a sort of phone cord, which begins to coil up on itself even as it's being manufactured. Foldit players are trying to figure out exactly how those coils fit together in a given protein.
Khatib decided that human intuition might succeed where high-powered computers and microscopes had failed. He gave the Foldit players a task: take the best available models of the mystery protein and see if you can actually figure out the structure correctly.
They did it in 10 days.
Now, Khatib says, his team can begin working on drugs that target the AIDS-causing protein.
"That's basically the essence of being able to solve proteins," he says. "Until you know exactly how they look like, you can't target them in any way with drugs."
The Foldit team isn't just trying to figure out the structure of existing proteins, it's working on designing brand-new ones. Right now, the game is challenging players to come up with a protein that could fight the flu.
"We can actually take the proteins that are designed by players in the game, and ... synthesize them in the lab, and actually make their designs real," Cooper says, "and see if they work as we expect them."
RACHEL MARTIN, host: When science fails, it's time to play games.
(SOUNDBITE OF MUSIC)
MARTIN: That's the sound of Foldit. It's a computer game, where players try to puzzle out the structure of a protein. The game was developed by scientists at the University of Washington, and it came in handy for another research team there that was trying to pin down a protein that causes AIDS in rhesus monkeys. The tiny particle had been a mystery for more than a decade even the most advanced imaging technology couldn't capture it.
So researchers asked the Foldit players to take a shot at predicting the structure. They solved the problem in just 10 days. The story of the gamers and the mystery protein appears in the journal "Nature's Structural and Molecular Biology" and I'm joined now by researcher Firas Khatib who co-wrote the paper, and the designer of the Foldit game Seth Cooper. Hey, guys. Thanks for joining us.
SETH COOPER: Thank you for having us.
FIRAS KHATIB: Thanks for having us, yeah.
MARTIN: So protein folding doesn't exactly sound like the makings of a good video game, does it? Let's start with you, Seth.
COOPER: Well, one of the really interesting things about protein folding is that it's all about how the pieces of the protein fit together. And they're all of these, like, little pieces and atoms that need to fit together in just the right way for the protein to fold. It's a lot like a 3D jigsaw puzzle or kind of like a 3D Tetris.
MARTIN: Basic science question coming your way, guys. Ready? Why are proteins folded and not built in some other way?
KHATIB: It's actually because that's how they fold up in nature when they come out of the ribosome where the proteins are built.
COOPER: Like a phone cord...
MARTIN: Like a phone cord.
COOPER: ...kind of.
KHATIB: Yeah, exactly. So you can imagine, you know, you have the phone cord maker making the phone cord, and it already starts winding itself up into, let's say, a helix, which is something that proteins totally fold up as.
MARTIN: Why, Firas, was it so hard to figure out the structure of this particular protein?
KHATIB: The experimental data had been worked on for over 14 years to try to basically have a high resolution structure to this protein and nothing was able to fit the experimental data. So there's all this ambiguity that unless you get a model that's close enough, the experimental data basically makes no sense, and you can't solve the structure. And proteins are so small you can't see them with a microscope.
KHATIB: So that's the other limitation that - you know, that's why our lab tries to use super computers to try to predict exactly how they'll fold. And interestingly, the structure was actually already solved using a different experimental method called NMR which uses a magnetic field to solve the structure. Those models weren't even good enough, and so that's actually the model that we gave to the Foldit players.
We basically gave them the 10 different NMR models as starting points and said, you know, we know these are wrong. They don't fit the data. Can you improve on them and just get us close enough? We sent the model to our Polish crystallographer collaborators, and they solved it immediately. And they literally emailed us back saying, this is one of the most joyous moments of my life.
(SOUNDBITE OF LAUGHTER)
KHATIB: And they insisted that we open champagne over Skype simultaneously. This is how excited they were about it.
MARTIN: And did you?
KHATIB: Of course.
MARTIN: Of course.
KHATIB: You don't say no to a champagne over Skype from Poland.
MARTIN: So, Firas, explain how this changes things. What will knowing the structure of this protein allow you to do?
KHATIB: We'll hopefully be able to design drugs and better antiretroviral drugs to block it. That's basically the essence of being able to solve proteins is until you know exactly how they look, you can't target them in any way with drugs.
MARTIN: So let's talk about it. I happen to have kind of a bad cough right now. Any kind of Foldit cure of the common cold game coming up?
KHATIB: Common cold is a little hard, but how about the flu? Would that be okay?
MARTIN: Okay, flu. I get the flu, sure.
KHATIB: Well, that's one of the new directions that we're going with Foldit is actually...
KHATIB: Yeah, protein design. So we're basically designing novel proteins that don't even exist in nature. And one of the proteins that we let them design was inhibitor for the flu.
COOPER: One of the really interesting things about the protein design part of the game that we've been working on recently is that we can actually take proteins that are designed by the players in the game and synthesize them in the lab and actually make their designs real and see if they, you know, work as we expect them.
MARTIN: That was Seth Cooper. He's the creative director at the University of Washington's Center for Game Science. He was joined by Firas Khatib. He's a post-doctoral researcher also at the University of Washington. You can find a link to the game Foldit on our website, npr.org. The two of them join me from member station KUOW in Seattle. Thanks so much for coming in, guys.
KHATIB: Thank you. Transcript provided by NPR, Copyright NPR.