Who: I am a life-sciences explorer.
What: I surf nutrient-to-gene trails.
Where: My base camp is at the University of Geneva.
When: - gianpaolo.rando@unige.ch,

Solve puzzles for science

In science, game-driven crowdsourcing makes 18 fold better

Because of sequential nature of mRNA translation, proteins begin as strings of 50-1000 amino acids that immediately fold into specific 3D-coiled structures. Understanding how proteins fold into unique three-dimensional shapes is a big quest. Just a small protein can fold in astronomical number of ways, so one of the hardest problems in biology today is to figure out, for each protein, which of the many possible structures is the most correct one. Scientists try to solve this jigsaw puzzle because it may help to understand how a protein carries out its job.

Computers make faster permutations, and different automatic algorithms try to estimate protein folding. Sometimes however, human creativity can outperform the computer processivity, so in 2008 a team of HHMI researchers at the University of Washington decided to take the arcane world of protein folding to the online gaming arena. Foldit is a free game in which players around the world compete to design proteins. Foldit attempts to predict the structure of a protein by taking advantage of humans puzzle-solving intuitions and having people play competitively to fold the best proteins.

Four years later, Nature Biotechnology is publishing today a study of the original team where Foldit players were challenged to ameliorate the structure of a Dies-Alderase enzyme, a protein holding great promises for the production of renewable fuels.
Here we report the use of game-driven crowdsourcing to enhance the activity of a computationally designed enzyme through the functional remodeling of its structure [...] Several iterations of design [...] increased enzyme activity >18-fold. X-ray crystallography showed that the large insertion adopts a helix-turn-helix structure positioned as in the Foldit model. These results demonstrate that human creativity can extend beyond the macroscopic challenges encountered in everyday life to molecular-scale design problems.

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Eiben et al., Nature Biotechnology 30, 190 (2012). doi:10.1038/nbt.2109