Citizen Scientists Discover Key HIV Protein

For years, scientists have been saying that some of the biggest discoveries in science will come from non-scientists. And now that prediction is showing promise as two teams of online video game players have helped solve the structure for an important enzyme found in the HIV virus.

After medical researchers had repeatedly failed to piece together the structure of a class of enzymes called retroviral proteases, they turned to the biology video game Foldit, an online puzzle that has users score points by folding proteins and ultimately helping science make key advances like this. The protease enzyme plays a critical role in how the AIDS virus matures and multiplies.

In the hunt for AIDS drugs and a vaccine, scientists are focused on blocking these enzymes but until now they have been stuck, trying to figure out what the molecule looks like.

Foldit was created in 2008 by computer scientists at the University of Washington Center for Game Science in collaboration with biochemist David Baker’s lab.

In the last three years the game has evolved. To piece together the retrovirus enzyme structure, Seth Cooper, the game’s co-founder says, “Gamers used a new alignment Tool for the first time to copy parts of known molecules and test their fit in an incomplete model.”

The puzzle they were working on was called “Unsolved Monkey Virus Protein” and within three weeks two teams had solved the problem, which Dr. Baker then took from the 3-D computer world into the real world.

For the monkey virus problem, Foldit players began with a scientific rough draft of the protease enzyme. During three weeks of play, hundreds of teams and individuals generated over a million structure predictions. And the solution, found by the winning team in 10 days, is nearly perfect. It gives Baker and his colleagues all the information they needed to pinpoint the structure down to almost the last atom.

Postdoctoral researcher Firas Khatib says, “It’s the power of citizen science.”

Before Foldit launched, Dr. Baker’s lab created a program called Rosetta@home which allowed computers to run simulated protein folding while the machines sat idle. It worked much like the SETI@home screensaver. Instead of searching for extra terrestrial signals from space it ran quick simulations of protein folding. It used distributed processing to crunch massive amounts of data but it was all automated. The user could just sit back and watch the process unfold.

Foldit came into being after some Rosetta users suggested that the computer was making wrong assumptions because it could only follow a logical path. And the solutions to these complex proteins probably required some intuition and exploration, two things a computer can’t stomach.

Once Dr. Baker’s lab combined the power of its artificial intelligence with human intelligence he stumbled on a winning combination that could lead to a cure for HIV and other diseases.

Foldit Contenders Group and Foldit Void Crushers Group are the two teams that received co-authorship on the protease structure paper which was just published in Nature Structural & Molecular Biology.

A member from the Foldit Contenders named “Mimi” says, “It is a team thing. Everybody contributes.”

And that’s just the motivation Dr. Baker is using to solve the big biological questions.

He says, “Competitive social interaction is a very strong driving force.”

Video all about Foldit (By the end you’ll want to sign up. It’s infectious.)