Predicting protein structures with a multiplayer online game.
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.
Cooper
Seth
S
Department of Computer Science and Engineering, University of Washington, Box 352350, Seattle, Washington 98195, USA.
Khatib
Firas
F
Treuille
Adrien
A
Barbero
Janos
J
Lee
Jeehyung
J
Beenen
Michael
M
Leaver-Fay
Andrew
A
Baker
David
D
Popović
Zoran
Z
Players
Foldit
F
D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D003196:Computer Graphics; D003198:Computer Simulation; D003299:Cooperative Behavior; D003463:Cues; D005717:Games, Experimental; D006126:Group Processes; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D021621:Imaging, Three-Dimensional; D020407:Internet; D007899:Leisure Activities; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010775:Photic Stimulation; D011340:Problem Solving; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013269:Stochastic Processes; D013816:Thermodynamics
D011506:Proteins