The Boston Globe recently asked, “What if you could play a video game that helps find a cure for cancer?”
For Assistant Professor Firas Khatib (Computer & Information Science), the answer is hopeful. The Globe piece follows the recent publication of a paper co-authored by Khatib in Nature that details how their game Foldit has brought citizen scientists together in the search for cures through protein building.
The project, led by the Institute for Protein Design at the University of Washington School of Medicine, is a multi-institutional effort to engage people from across the world and across education levels in solving many different medical issues. The easiest way to find solutions and cures is through creating new proteins.
“There are more possible proteins than there are atoms in the universe. It’s exciting to think that now anyone can help explore this vast space of possibilities,” said senior author David Baker, professor of biochemistry at the UW School of Medicine and director of the Institute for Protein Design.
“The diversity of molecules that these gamers came up with is astonishing,” said lead author Brian Koepnick, a postdoctoral researcher at the UW Medicine Institute for Protein Design. “These new proteins are by no means inferior to the stuff a PhD-level scientist might make.”
Foldit was created in 2008 as a way to ‘gamify’ protein research. Proteins are essential biomolecules found inside every cell of every organism. Their intricate three-dimensional structures give rise to their diverse functions, which include digestion, wound healing, autoimmunity and much more. Through gameplay, Foldit players have 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 proteins that already exist—there was no way to design new ones.
To learn more about the Foldit project, listen to Professor Khatib and his fellow researcher Seth Cooper’s TEDx Talk.
“We didn’t give [Foldit players] any lectures or tell them to read anything. Instead, we tweaked the code that runs the game over many years,” said senior author Firas Khatib, assistant professor of computer science at the University of Massachusetts Dartmouth.
The scientists tested 146 proteins designed by Foldit players in the laboratory. Fifty-six were found to be stable, suggesting the gamers had indeed produced some realistic proteins. The team collected enough data on four of these new molecules to show that designs did, in fact, adopt their intended structures.
“Designing completely new proteins that didn’t exist in nature has been our goal with Foldit for a long time,” said senior author Seth Cooper, assistant professor in the Khoury College of Computer Sciences at Northeastern University. “This new set of results shows that it’s possible.”
Creating new proteins is a bit like trying to tie never-before-seen knots using rope that is a million times thinner than a human hair. To date, only a small group of experts with intimate knowledge of the way biomolecules twists and turn bothered with this exceedingly complex task. Most use automated molecular design algorithms, and most design algorithms fail far more often than they succeed.
“We are always trying to make the algorithms better, but the human element is key,” said Khatib. “In fact, through Foldit design, players have even discovered flaws in the Rosetta energy function — our state-of-the-art method for protein design.”
Protein design is an emerging scientific discipline. In just the past five years, experts at the UW have created proteins that stimulate the immune system to fight cancer and others that act as potent vaccine candidates. In April, the Institute for Protein Design received a commitment of $45 million in funding through The Audacious Project, a philanthropic collaborative organized by TED, to design protein-based vaccines, medicines, and materials. Foldit was supported by the National Science Foundation and the National Institutes of Health.
“I never would have believed they would get that good, but Foldit players never cease to amaze us,” said Khatib.