Foldit is a revolutionary new multiplayer online computer game that engages non-scientists in solving hard prediction problems, enabling you to contribute to important scientific research. Foldit players interact with protein structures using direct manipulation tools and user-friendly versions of algorithms from the Rosetta structure prediction methodology, while they compete and collaborate to optimize the computed energy.
Here are the basic principles to keep in mind when folding proteins. Your score on each protein is based on how well you do with these three things:
# Pack the protein: The smaller the protein, the better. More precisely, you want to avoid empty spaces (voids) in the structure of the protein where water molecules can get inside. So you want the atoms in the protein to be as close together as possible. Certain structures, such as sheets, will even connect together with hydrogen bonds if you line them up right and get them close together. This is also good. Key word: Compact.
# Hide the hydrophobics: Hydrophobics are the sidechains that don't want to be touching water, just like oil or wax. Since most proteins float around in water, you want to keep the hydrophobics (orange sidechains) surrounded by as many atoms as possible so the water won't get to them. The other side of this rule is that hydrophilics (blue sidechains) do want to be touching water, so they should be exposed as much as possible. Key word: Buried.
# Clear the clashes: Two atoms can't occupy the same space at the same time. If you've folded a protein so two sidechains are too close together, your score will go down a lot. This is represented by a red spiky ball (clash) where the two sidechains are intersecting. If there are clashes, you know something is wrong with your protein. So make sure everything is far enough apart. Key word: Apart.
The current series of Science Puzzles, the Grand Challenges, are meant to generate the evidence needed to prove that human protein folders can be more effective than computers at certain aspects of protein structure prediction. That's what all the puzzles in Foldit are about right now: predicting the structure of a protein based on its amino acid sequence. The three rules mentioned above describe the characteristics of correct protein structures.
Resource Type: Resource
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Fold It, Foldit: Solve Puzzles for Science
NSF, DARPA, Howard hughes medical institute, Microsoft, NVIDIA, IIS0811902, 0906026, N00173-08-1-G025,
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community building portal, software resource
Created 4 years ago by Anonymous
People exert large amounts of problem-solving effort playing computer games. Simple image- and text-recognition tasks have been successfully 'crowd-sourced' through games, but it is not clear if more complex scientific problems can be solved with human-directed computing. Protein structure prediction is one such problem: locating the biologically relevant native conformation of a protein is a formidable computational challenge given the very large size of the search space. Here we describe Foldit, a multiplayer online game that engages non-scientists in solving hard prediction problems. Foldit players interact with protein structures using direct manipulation tools and user-friendly versions of algorithms from the Rosetta structure prediction methodology, while they compete and collaborate to optimize the computed energy. We show that top-ranked Foldit players excel at solving challenging structure refinement problems in which substantial backbone rearrangements are necessary to achieve the burial of hydrophobic residues. Players working collaboratively develop a rich assortment of new strategies and algorithms; unlike computational approaches, they explore not only the conformational space but also the space of possible search strategies. The integration of human visual problem-solving and strategy development capabilities with traditional computational algorithms through interactive multiplayer games is a powerful new approach to solving computationally-limited scientific problems.