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Online Game Players' Solution May Lead to HIV Vaccine

Science-minded gamers learn to fold HIV protein that stumped researchers for 15 years

Online Game Players' Solution May Lead to HIV Vaccine

SEATTLE—Remember the human immunodeficiency virus, better known as HIV? It's a retrovirus that's been around for a few years, and in those who contract it, it enters various cells that control the body's immune system adn replicates rapidly, decreasing the number of such cells and leaving the infected person vulnerable to a whole host of diseases that a healthy body could otherwise fight off.

Researchers have been studying HIV, which has killed more than 25 million people, since it was first discovered in 1981, and while several treatment methods have been devised, several using what are termed "protease inhibitors," there currently is no cure for the disease.

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But that may soon change. According to PC magazine, players of an online scientific game called FoldIt, in which the gamers compete to fold proteins—long three-dimensional chains of anywhere from 100 to 1,000 amino acids, the building blocks of cells—into their most stable (and hence workable) forms, have now deciphered the structure of a key protein, retroviral protease, that allows HIV to replicate itself within the living cells of rhesus monkeys—a structure that scientists have been trying to figure out for more than 15 years—and the gamers accomplished it in a matter of days.

FoldIt, which was devised by researchers at the University of Washington, enlists online game players to examine the structure of proteins, which the game's website describes as "the workhorses in every cell of every living thing."

"[K]nowing the structure of a protein is key to understanding how it works and to targeting it with drugs," the site explains. "The number of different ways even a small protein can fold is astronomical because there are so many degrees of freedom. Figuring out which of the many, many possible structures is the best one is regarded as one of the hardest problems in biology today and current methods take a lot of money and time, even for computers. Foldit attempts to predict the structure of a protein by taking advantage of humans' puzzle-solving intuitions and having people play competitively to fold the best proteins. Since proteins are part of so many diseases, they can also be part of the cure. Players can design brand new proteins that could help prevent or treat important diseases."

In particular, the site notes, "HIV-1 protease and reverse transcriptase are two proteins made by the HIV virus that help it infect the body and replicate itself. HIV-1 protease cuts the 'polyprotein' made by the replicating virus into the functional pieces it needs. Reverse transcriptase converts HIV's genes from RNA into a form its host understands, DNA. Both proteins are critical for the virus to replicate inside the body, and both are targeted by anti-HIV drugs."

What some of the FoldIt players did is to predict the structure of the protein "retroviral protease" in such detail that researchers were able to use that model in their research, as set forth in an article to be published in the magazine Nature Structural & Molecular Biology, and made available online today for a fee (.pdf).

"Following the failure of a wide range of attempts to solve the crystal structure of M-PMV retroviral protease by molecular replacement, we challenged players of the protein folding game Foldit to produce accurate models of the protein," the study, authored by an international group of FoldIt players, reads. "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."

It is, of course, too soon to tell just what advances toward an HIV cure the FoldIt players' breakthrough will generate—but it is undoubtedly already giving online game players a response to their parent's/spouse's complaint, "Hey, why don't you stop playing that stupid video game and do something useful?"






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Mark Kernes

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