Proteins are composed of a long chain of amino acids that fold up into various shapes—blobs, coils, etc.—based on the chemical properties of each link along these chains. The final three-dimensional shape a protein adopts is essential for its activity, whether that activity involves catalyzing chemical reactions or providing a structural function. The folding process is determined by energy: the protein folds in such a way that it adopts the lowest-energy state.
FoldIt put a video game-style interface on the process of finding this minimal energy state, and a very active community of players have used that interface to successfully find the protein structures that represent low-energy states. But finding out what already exists isn’t the only protein folding challenge that has interested biologists.
Many proteins, called enzymes, are extremely efficient catalysts, accelerating the rates of chemical reactions by many orders of magnitude. It would be nice to design a protein that gives some key commercial reactions that sort of boost, so scientists have attempted to do so in the past, with mixed success. But the team behind FoldIt was confident, and it decided to see if it could crowdsource a new protein design.
The team chose an advanced FoldIt player to act as a liaison with the community, and set to work providing them challenges based on some initial ideas on how the enzyme could be improved. For example, one side of the area where the chemical reaction takes place (called the “active site”) was open to the environment. Researchers set up a “Cover the ligand” challenge that asked players to remodel the area around the active area so that it closed over the site.
For the most part, the results were disappointing—most of the suggested solutions were completely inert, and one of the most successful was actually less active than the original enzyme. But the authors used that work as a starting point to get players to create new variants. By the time they were done, the redesigned enzyme was 100 times more active, leaving it better at catalyzing the reaction than the original enzyme.