Successful CASP9 predictions by the Foldit Void Crushers Group. (a) Starting from the fourth-ranked Rosetta Server model (red) for CASP9 target T0581, the Foldit Void Crushers Group (yellow) generated a model that was closer to the crystal structure later determined (blue). (b) Starting from a modified Rosetta model built using the Alignment Tool (red), the Foldit Void Crushers Group generated a model (yellow) considerably closer to the later determined crystal structure (blue). Images were produced using PyMOL software (http://www.pymol.org).
Players of the video game Foldit, a protein modeling program, have unlocked the structure of the protein CASP9, which is involved in the virus that causes simian AIDS. The breakthrough has eluded laboratory scientists for 15 years, yet, amazingly, the teams of gamers that worked on the problem needed just three weeks to make the correct decisions regarding the structure.
The difference maker, according to researchers who had previously worked on the problem, was the ability of Foldit and its users to make large-scale changes to the structure on a rapid basis. Previous modeling efforts conducted on dedicated supercomputers had locked researchers into certain assumptions on the most likely structure. Their ability to test variations on these assumptions was limited. The scope of Foldit allowed a much greater degree of freedom with regard to CASP9.
Recently confirmed by x-ray crystallography and published in Nature Structural & Molecular Biology, the finding illustrates the experimental potential of Foldit, a computer program developed at the University of Washington several years ago. Built by many of the same people that developed the Rosetta@home utility. Foldit allows users to not only contribute their personal computer’s computation power to the modeling of proteins, but also contribute their brains’ 3-D pattern-matching abilities to the complex problem of protein folding.