Maybe I wasn't wasting my childhood after all!
Foldit is a multiplayer online game that enlists players worldwide to solve difficult protein-structure prediction problems. Foldit players leverage human three-dimensional problem-solving skills to interact with protein structures using direct manipulation tools and algorithms from the Rosetta structure prediction methodology1. Players collaborate with teammates while competing with other players to obtain the highest-scoring (lowest-energy) models. In proof-of-concept tests, Foldit players—most of whom have little or no background in biochemistry—were able to solve protein structure refinement problems in which backbone rearrangement was necessary to correctly bury hydrophobic residues2. Here we report Foldit player successes in real-world modeling problems with more complex deviations from native structures, leading to the solution of a long-standing protein crystal structure problem.
To determine whether human intuition could succeed where automated methods had failed, we challenged Foldit players to build accurate models of M-PMV PR starting from the NMR coordinates (which had failed in MR tests; see Supplementary Discussion and Supplementary Fig. 3). When the 3-week competition concluded, we screened the top-scoring Foldit models using Phaser11 to determine whether any were of sufficient quality for MR. Remarkably, despite the complete failure of all previous approaches, several solutions by the Foldit Contenders Group produced phase estimates that were good enough to allow a rapid solution of the crystal structure.
Years ago I suggested that the simulations of reality in video games were becoming good enough to serve as effective teaching tools. I did not, however, envision a time when they would be able to actually help advance human knowledge.