In what might be a significant breakthrough in HIV/AIDS research, online gamers playing a game called Foldit have cracked a key protein structure problem that has had scientists scratching their heads for years. And the gamers did it in three weeks. You can read a scientific account of how researchers recruited Foldit players to work on the modeling problem and ultimately solve the crystal structure of M-PMV retroviral protease in a paper published online this week in the journal Nature Structural & Molecular Biology.

Foldit invites players to predict protein structures. The game was developed by researchers at the University of Washington, as a deliberate way to get gamers to compete by solving scientific problems. The game requires they use spatial and critical thinking skills to build 3D models of protein molecules. In this case, they were invited to build models of M-PMV, a protease enzyme that plays a key role in how a virus similar to HIV replicates in cells. Few of the players had any background in biochemistry.

By solving the mystery of the 3D structure of the protein, the gamers have helped scientists move a step forward in developing a drug that could stop viruses like HIV from spreading.

The researchers write:

“Remarkably, Foldit players were able to generate models of sufficient quality for successful molecular replacement and subsequent structure determination. The refined structure provides new insights for the design of antiretroviral drugs.”

The study is a good example of how people skilled at video games can get involved in science and help solve a wide range of problems.

In Foldit, the gamers try to predict how proteins fold themselves. When the gamers are playing the game, their actions to try and solve the problem are recorded and used to create algorithms to help computers increase their spatial reasoning.

Solving problems in the game helps scientists gain a better understanding of how cells make protein, a process call biosynthesis. A particular challenge in this field is understanding how certain proteins fold into three-dimensional structures.

To win, gamers have to do well in three factors: how well you pack the protein in 3D, how efficiently you hide the hydrophobic bits of the molecule, and how you resolve the clashes. The gamers don’t have to understand these factors in this way to play the game.

The game presents them with a new protein and away they go, trying to bend it around to find its ideal form. When they hit a correct move, that hits these factors, they get points. The gamers are able to chat to each other online and compare solutions. It was through sharing strategies that gamers around the world solved the M-PMV problem.

Seth Cooper, lead designer of Foldit and co-author of the paper, told the press:

“People have spatial reasoning skills, something computers are not yet good at.”

“Games provide a framework for bringing together the strengths of computers and humans,” he added.

Written by Catharine Paddock PhD