Foldit is a multiplayer online game in which non-specialist participants use three-dimensional problem-solving skills to manipulate protein structures in order to obtain the highest scoring (lowest-energy) model. Khatib et al. report that Foldit has been used to solve the structure of the retroviral protease (Pro) of Mason–Pfizer monkey virus (MPMV), a simian AIDS-causing virus. Despite MPMV Pro crystallizing as a monomer (rather than in its active, dimeric form), determining its structure by molecular replacement using either homodimer models or NMR data has been problematic for more than a decade. In a 3-week competition, Foldit players generated several models that were good enough to allow for the solution of a crystal structure. This structure revealed several features about the putative Pro dimer interface that provide opportunities for the design of new antiretroviral drugs. These efforts reveal the potential for harnessing interest in online gaming to help solve real-world scientific problems.
ORIGINAL RESEARCH PAPER
Khatib, F. et al. Crystal structure of a monomeric retroviral protease solved by protein folding game players. Nature Struct. Mol. Biol. 18 Sep 2011 (doi:10.1038/nsmb.2119)