Gamers, citizen science, and protein structures (Video link)

From the beginning, protein design has played a key role in proposals for developing advanced nanotechnology, or molecular manufacturing (see the Technology Roadmap for Productive Nanosystems). Designing proteins and predicting protein structure from sequence are both very difficult problems of immense importance to both biotechnologists and nanotechnologists. One novel approach is an online game called Foldit, developed in the laboratory of Dr. David Baker of the University of Washington, Department of Biochemistry, co-winner of the 2004 Feynman Prizes in Nanotechnology for Theory. Foldit players work to predict the structure of protein molecules of unknown structure. Thanks to ScienceDaily for pointing to this EurekAlert! article, written by Leila Gray “Gamers succeed where scientists fail: Molecular structure of retrovirus enzyme solved, doors open to new AIDS drug design“:

Gamers have solved the structure of a retrovirus enzyme whose configuration had stumped scientists for more than a decade. The gamers achieved their discovery by playing Foldit, an online game that allows players to collaborate and compete in predicting the structure of protein molecules.

After scientists repeatedly failed to piece together the structure of a protein-cutting enzyme from an AIDS-like virus, they called in the Foldit players. The scientists challenged the gamers to produce an accurate model of the enzyme. They did it in only three weeks.

This class of enzymes, called retroviral proteases, has a critical role in how the AIDS virus matures and proliferates. Intensive research is under way to try to find anti-AIDS drugs that can block these enzymes, but efforts were hampered by not knowing exactly what the retroviral protease molecule looks like.

“We wanted to see if human intuition could succeed where automated methods had failed,” said Dr. Firas Khatib of the University of Washington Department of Biochemistry. Khatib is a researcher in the protein structure lab of Dr. David Baker, professor of biochemistry.

Remarkably, the gamers generated models good enough for the researchers to refine and, within a few days, determine the enzyme’s structure. Equally amazing, surfaces on the molecule stood out as likely targets for drugs to de-active the enzyme.

“These features provide exciting opportunities for the design of retroviral drugs, including AIDS drugs,” wrote the authors of a paper appearing Sept. 18 in Nature Structural & Molecular Biology [abstract]. The scientists and gamers are listed as co-authors.

This is the first instance that the researchers are aware of in which gamers solved a longstanding scientific problem. …

The solution of the virus enzyme structure, the researchers said, “indicates the power of online computer games to channel human intuition and three-dimensional pattern matching skills to solve challenging scientific problems.”

With names like Foldit Contenders Group and Foldit Void Crushers Group, the gamer teams were fired up for the task of real-world molecule modeling problems. The online protein folding game captivates thousands of avid players worldwide and engages the general public in scientific discovery. …

UWTV has placed a video explaining Foldit on YouTube. There is an excellent, detailed article by Alan Boyle explaining the work on MSNBC. There are other excellent articles by Jef Akst at The Scientist and by Leslie Horn at PCMag. The research article is not open access, but the authors themselves have posted the PDF for the published paper and linked to it at the Foldit portal. The portal mentions two more papers in the pipeline, including “a brand new synthetic protein discovered primarily due to the insight of Foldit protein design. Stay tuned.” Stay tuned indeed.

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