The players of the online protein-folding game Foldit (which we’ve reported on before) outperformed scientists by discovering the structure of a protein involved in the Mason-Pfizer monkey virus (M-PMV). The M-PMV is a retrovirus, like HIV, that causes AIDS in monkeys and apes. Understanding its structure will help researchers develop antiretroviral drugs that can fight HIV—but this has been a mystery for over a decade.

Now, with the help of groups of (generally) non-scientist players and their pattern-recognition skills, scientists from the University of Washington have joined with groups including "Foldit Contenders Group" and "Foldit Void Crushers Group" to model the crystal structure of the M-PMV retroviral protease (PR), a protein responsible for viral growth.

What exactly is protein folding, and how are gamers doing it? Our earlier article on Foldit does a great job explaining both, but I’ll briefly summarize here.

Proteins consist of long chains of amino acids, molecules made up of carbon, hydrogen, oxygen, and nitrogen. Figuring out the order of the amino acids is easy, but that's only part of the story—the amino acid chain folds into complex shapes that determine the function of the protein. Due to the incredibly high number of degrees of freedom, understanding this structure is one of the hardest problems in modern science. A lot of research has focused on designing programs dedicated to solving this problem, which is mainly an energy minimization task (the correct shape is the most stable, the one with the lowest energy).

Minimization algorithms only work so well, however. The idea behind Foldit is that human pattern recognition and problem solving skills can succeed where the algorithms fail. The group's first publication described this success; now, Foldit’s players have solved an important problem related to AIDS research.

The actual protein they considered is a protease, an enzyme that cuts up other proteins In retroviruses like M-PMV and HIV. It's a necessary component of the virus' life cycle. Because of this important role, protease inhibitors have been the subject of intense drug development, and understanding the exact structure of the protease could help this effort immensely.

The Foldit players were given ten different, incorrect models as a starting place. Over the course of sixteen days, players tweaked the designs, coming up with tens of thousands of variations. Then, the breakthroughs: a player named "spvincent" came up with a structure much better than any previous iteration, and two more players ("grabhorn" and "mimi") quickly improved on it. With a few more days of work, the researchers completed the solution. Achievement unlocked, indeed.

In fact, according to the Foldit website, the research team is currently working on at least two more papers based on the game’s success. One will take the recipes (sets of interactions between proteins) created by Foldit players, and compare them to those from state-of-the-art algorithms. Another describes an entirely new synthetic protein discovered with the help of Foldit.

What does the future hold for gaming-inspired citizen science? It doesn’t take a huge leap of imagination to picture gold-farmers converted to protein-folders. If scientific problems can be turned into something fun and easy-to-use (like Foldit), and offer Achievements or Trophies to show off, perhaps the legions of gamers could spend their free time a bit more productively, solving important scientific problems.

Nature Structural & Molecular Biology, 2011. DOI: 10.1038/nsmb.2119 (About DOIs)