Gamers Solve Protein Structure

Players of the online computer game Foldit have succeeded in solving a retroviral protease crystal structure that had eluded scientists for years (Nat. Struct. Mol. Biol., DOI: 10.1038/nsmb.2119). Foldit grew out of the distributed computing program Rosetta@home, run by David Baker of the University of Washington, Seattle, in which individuals donate computing power to solve problems in protein folding and design. Foldit players—alone or in teams—compete to find a protein’s lowest energy state within the allotted time. With many proteins, Foldit players run into the same problems that plague other computational methods, getting trapped by local minima in the energy landscape. But Foldit also shows great promise. For example, players were asked to optimize the crystal structure of Mason-Pfizer monkey virus (M-PMV) retroviral protease. Despite having X-ray diffraction data, scientists have been unable to solve the structure because they lacked appropriate crystallographic phase information. Starting with 10 poorly scoring NMR models, one of the teams, the Foldit Contenders group, built on each other’s models, ultimately producing one that solved the phase problem. Within days, scientists had the final structure.