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Protein-Folding as a Computer Game

Posted by Josh Rothman  September 26, 2011 08:36 AM

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A huge team of computer gamers, working collaboratively over the internet, appear to have solved a long-standing science puzzle: Using the online protein-folding game Foldit, they've figured out the structure of a protein crucial to the functioning of the HIV-like Mason-Pfizer monkey virus, which causes AIDS in monkeys. The paper, "Crystal structure of a monomeric retroviral protease solved by protein folding game players," was recently published in Nature Structural & Molecular Biology; the discovery may contribute to new HIV research.

Proteins are the heavy equipment of the cellular world -- once they're assembled according to instructions stored in DNA, they do all the moving, transporting, signaling, and interacting. They have complex three-dimensional structures which, unfortunately, are often nearly impossible to figure out, because computers are not very good at going from a two-dimensional microscope image to a three-dimensional model. Ed Yong of It's Not Exactly Rocket Science explains how Firas Khatib, of the University of Wisconsin, harnessed a team of gamers to solve this particular protein:

These [HIV-like] viruses create many of their proteins in one big block. They need to be cut apart, and the viruses use a scissor enzyme -- a protease -- to do that. Many scientists are trying to find drugs that disable the proteases. If they don’t work, the virus is hobbled -- it’s like a mechanic that cannot remove any of her tools from their box.

To disable M-PMV’s protease, we need to know exactly what it looks like. Like real scissors, the proteases come in two halves that need to lock together in order to work. If we knew where the halves joined together, we could create drugs that prevent them from uniting. But until now, scientists have only been able to discern the structure of the two halves together. They have spent more than ten years trying to solve structure of a single isolated half, without any success.

The gamers, working in Foldit, were able to figure out that structure, which has been verified with high-powered microscopes.

How useful will the discovery be? It depends upon the similarities between this virus and HIV. The paper shows one thing for certain: While computers are still being programmed to understand how objects work in space, human beings have evolved, over millions of years, tremendous spatial reasoning skills. Ultimately, it's that evolved spatial intuition that's being harnessed by Foldit.

[More: Jane McGonigal, at TED, on how gaming can make a better world.]

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About brainiac Brainiac is the daily blog of the Globe's Sunday Ideas section, covering news and delights from the worlds of art, science, literature, history, design, and more. You can follow us on Twitter @GlobeIdeas.
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Leon Neyfakh is the staff writer for Ideas. Amanda Katz is the deputy Ideas editor. Stephen Heuser is the Ideas editor.

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Guest blogger Joshua Glenn is a Boston-based writer, publisher, and freelance semiotician. He was the original Brainiac blogger, and is currently editor of the blog HiLobrow, publisher of a series of Radium Age science fiction novels, and co-author/co-editor of several books, including the story collection "Significant Objects" and the kids' field guide to life "Unbored."

Guest blogger Ruth Graham is a freelance journalist in New Hampshire, and a frequent Ideas contributor. She is a former features editor for the New York Sun, and has written for publications including Slate and the Wall Street Journal.

Joshua Rothman is a graduate student and Teaching Fellow in the Harvard English department, and an Instructor in Public Policy at the Harvard Kennedy School of Government. He teaches novels and political writing.

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