Video players design new proteins

A team of researchers has coded its expertise in the Foldit computer game to enable citizen scientists to successfully design synthetic proteins for the first time.

The first results of this collaboration appear in the June 5 issue of Nature. The Institute for Protein Design at the University of Washington School of Medicine led the multi-institutional effort.

"There are more proteins available than there are atoms in the universe, so it's exciting to think that everyone can help explore this vast space." of opportunities, "said David Baker, senior co-author, professor of biochemistry at the UW School of Medicine and director. from the Institute for Protein Design.

"The diversity of molecules offered by these players is amazing," said lead author Brian Koepnick, a postdoctoral researcher at the Institute for Protein Design. "These new proteins are by no means inferior to those that a Ph.D. level scientist could manufacture."

Foldit was created in 2008 with the aim of "gamifying" protein research. Proteins are essential biomolecules found in every cell of every organism. Their complex three-dimensional structures give rise to various functions including digestion, wound healing, autoimmunity and much more.

Thanks to the gameplay, Foldit players helped determine the structure of an HIV-related protein and improved the activity of useful enzymes. Until now, however, Foldit players could only interact with already existing proteins. There was no way to design new ones.

"For a long time, Foldit's goal has been to design totally new proteins that did not exist in nature," said Seth Cooper, co-senior author, assistant professor at Khoury College of Computer Sciences of the United States. Northeastern University. "This new set of results shows that it is possible."

To transform Foldit into a protein design platform, the researchers coded biochemical knowledge into the game. Thus, designer molecules that performed well in Foldit would be more likely to fall back as expected in the real world.

"We did not give [Foldit players] lectures or tell them to read anything. Instead, we tweaked the code that made the game run for many years, "said Firas Khatib, co-lead author, assistant professor of computer science at the University of Massachusetts Dartmouth.

Scientists tested 146 proteins designed by Foldit actors in the laboratory. 56 have been stable. This discovery suggests that the players produced realistic proteins. The researchers gathered enough data on four of these new molecules to show that the designs had adopted the intended structures.

"I never would have thought that they would get such a result, but the Foldit players will never stop to amaze us." said Khatib.

Making new proteins, it's a bit like trying to make new knots with a rope a thousand times thinner than a human hair. To date, only a small group of experts with deep knowledge of how biomolecules twist and become entangled in this extremely complex task. Most use automated molecular design algorithms and fail much more often.

"We are always trying to improve the algorithms, but the human element is the key," Khatib said. "In fact, thanks to the Foldit design, players have even discovered flaws in the energy function of Rosetta, our cutting-edge method for protein design."

Protein design is an emerging scientific discipline. Over the past five years, experts from the Institute for Protein Design and their colleagues have created proteins that boost the immune system to fight cancer and others that act as potent vaccine candidates. In April, the Institute for Protein Design received $ 45 million in funding through the bold project, a philanthropic collaboration organized by TED, to design vaccines, drugs and equipment-based of proteins.

Could players create the next star drug?

"Foldit players are a new addition to the arsenal of research," Khatib said. "They are not a quick fix, but they are an incredible resource."

Anyone interested in helping solve puzzles for science can learn more at fold.it/portal/