Gamers crack retroviral protease code
Online gamers deciphering of a protein key to the replication of both the human immunodeficiency and feline immunodeficiency viruses is an important step in identifying new drugs to treat the viruses, according to a FIV expert.
In a study published online Sept. 18, 2011 in the journal Nature Structural and Molecular Biology, researchers showed how online gamers decoded the model of the M-PMV protein, an enzyme important in the multiplication of HIV and FIV.
The protein is retroviral protease, a protease that breaks down other proteins and enables the replication of HIV and FIV. Research has shown HIV and FIV to have similarities in the binding modes of their inhibitor molecules.
John Elder, Ph.D., has studied FIV and its parallels with HIV for 25 years. His lab, located in the Department of Molecular Biology at The Scripps Research Institute in La Jolla, CA, focuses on the pathogenesis of FIV.
Elder said that while the development of HIV inhibitors is helpful, the solving of the M-PMV structure is but one step in the fight against HIV and FIV.
"There are already very detailed structures of HIV and FIV proteases and many drug-resistant variants, so the solving of the M-PMV structure - a distant relative of HIV and FIV - is not a major advance," Elder said. "However, there are many, many proteins of unknown structure that, if we can develop programs like Foldit that can yield meaningful structures… [great] strides can be made in identifying additional targets for drug development."
In the game, gamers try to predict how proteins fold themselves. As the gamers play, their problem-solving actions are recorded and used for an algorithm that can help computers increase their spatial reasoning.
Developed by researchers atthe University of Washington Center for Game Science, the game requires players to use spatial and critical thinking skills to construct 3D models of protein molecules.
"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 reads.
According to thestudy, the model structure the gamers produced could offer new insights in designing antiretroviral drugs.
"Remarkably, Foldit players were able to generate models of sufficient quality for successful molecular replacement and subsequent structure determination," the study reads. "The refined structure provides new insights for the design of antiretroviral drugs."
Gamers must do well in three areas in order to win: Packing the protein in 3D, hiding the hydrophobic bits of molecule and resolving the clashes. In the game, gamers must try to bend a new protein to find its ideal form, earning points as they hit each of the three different areas.
The three week game invited players to construct models of M-PMV, a protease enzyme related to HIV and FIV.
Elder said it is encouraging to see human intuition being introduced back into the equation.
"That, in itself, is an important move forward and at least turns us away from what has been a trend toward letting a computer plug and chug at a problem, hoping the answer would come out the other end," Elder said.
However, the importance of the science behind the Foldit program is not to be underestimated. While gamers did solve the structure, the science and biological aspects behind their solution are still important.
"I would certainly hope that people will appreciate the amount of science it took to develop the Foldit program and the scientific acumen it takes to know when the answer is right," Elder said.
TheFoldit game marks a new trend of "citizen science" in which Internet users do tasks that computers aren’t able to easily do.