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.

We have devised protein-folding sensors that link protein stability to TEM-1 β-lactamase activity. Addition of osmolytes and other compounds with chemical chaperone activity to the growth media of bacteria containing these sensors increases β-lactamase activity up to 207-fold in a dosedependent manner. This enables the rapid detection and sensitive quantification of compounds that enhance in vivo protein stability.

Nature Communications 7: Article number:12549 (2016); Published 16 September 2016; Updated 25 October 2016 The original version of this Article contained an error in the spelling of a member of the University of Michigan students Consortium, Sam Lee, which was incorrectly given as Sam Lewe. This hasnow been corrected in both the PDF and HTML versions of the Article.