Determining crystal structures through crowdsourcing and coursework

Abstract

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality.

Artificial intelligence in oncology

“…Numerous international competitions are held each year to further revolutionize the role of AI in health care (Table 2) and have yielded novel algorithms to tackle complicated tasks. Together with crowdsourcing, 65 such open and innovative challenges will broaden further applications of AI to cancer research. On the basis of recent advances, the FDA has finally begun the approval of clinical medical devices based on deep learning (Table 2).…”

Repurposing citizen science games as software tools for professional scientists

“…The game requires downloading and installation to play. Since the game’s release in 2008, Foldit players have contributed to a variety of areas in computational structural biochemistry research [13, 16, 21, 24]. Foldit presents a graphical, interactive front-end to the powerful Rosetta Molecular Modeling Suite [28, 37], which handles the game’s underlying protein model manipulations and scoring.…”

Crowd sourcing difficult problems in protein science*

“…The result of this contest allowed the protein to be identified as a member of the histidine triad protein family. 19 Foldit was also used for protein design. Players were asked to improve the activity of a computationally designed enzyme that catalyzes the Diels-Alder reaction.…”

“…The best structure produced in the competition was a structure from Foldit, which showed improved side‐chain conformations compared to the best structure produced by the trained crystallographers. The result of this contest allowed the protein to be identified as a member of the histidine triad protein family …”