Foldit may not have the nostalgia of Pac-Man, the zazz of World of Warcraft, or the iconic Mario Bros. characters, but its players do help researchers — and those gamers have achieved a new high score. Foldit players have created what researchers at the University of Washington are calling the first ever crowdsourced protein redesign, reports Nature News' Jessica Marshall. While previous Foldit successes have been in the realm of protein folding, its players have now progressed into protein design, creating an enzyme "with more than 18-fold higher activity than the original," Marshall says.
The study, published in Nature Biotechnology, involves an enzyme that catalyzes Diels-Alder reactions in synthetic chemistry. "Members of this huge family of reactions are used throughout industry to synthesize everything from drugs to pesticides, but enzymes that catalyze Diels-Alder reactions have been elusive," Marshall says. In 2010, the UW researchers tried to design a Diels-Alder enzyme from scratch, but were unsuccessful — so, they turned to Foldit players for help. "In one puzzle, the researchers asked users to remodel one of four amino-acid loops on the enzyme to increase contact with the reactants. In another puzzle, players were asked for a design that would stabilize the new loop," Marshall says. "The researchers got back nearly 70,000 designs for the first puzzle and 110,000 for the second, then synthesized a number of test enzymes based on the best designs, ultimately resulting in the final, 18-fold-more-active enzyme." While there are no current applications for the reaction the new enzyme catalyzes, the researchers say that it shows what crowdsourcing can do for scientific research, she adds.