Foldit

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Foldit
Developer(s)University of Washington
(Center for Game Science, Department of Biochemistry)
Initial releaseMay 8, 2008
Operating systemCross-platform
(Microsoft Windows, Mac OS X, Linux)
Size~43 MB
Available inEnglish, Russian, French
(6 others)
TypePuzzle video game, Protein folding
LicenseFreeware for academic and non-profit use [1]
Websitehttp://fold.it/

Foldit is an online puzzle video game about protein folding. The game is part of an experimental research project, and is developed by the University of Washington's Center for Game Science in collaboration with the UW Department of Biochemistry. The objective of the game is to fold the structure of selected proteins to the best of the player's ability, using various tools provided within the game. The highest scoring solutions are analysed by researchers, who determine whether or not there is a native structural configuration (or native state) that can be applied to the relevant proteins, in the "real world". Scientists can then use such solutions to solve "real-world" problems, by targeting and eradicating diseases, and creating biological innovations.

History

Rosetta

David Baker, a protein research scientist at the University of Washington, is responsible for beginning the Foldit project. Prior to the project's commencement, Baker and his laboratory co-workers relied upon another research project, Rosetta, to predict the native structures of various proteins, using special computer protein structure prediction algorithms. The project was eventually extended to utilize the processing power of user's personal computers, by developing a distributed computing program; Rosetta@home. The Rosetta@home program was made available for public download, and was designed to display progress of a particular protein being worked on at the time, as a screensaver. The results of the program's prediction routines are sent to a central project server, for verification.[1]

Some users of Rosetta@home became frustrated with the program when they realised they could see ways of solving the protein structures themselves but could not interact with the program. When Baker realised that humans could have considerable potential over computers attempting to solve protein structures, he approached David Salesin, a fellow computer scientist, and Zoran Popović, a game designer studying at the same university, to help conceptualize and build an interactive program that would both appeal to the public and assist in their efforts to find the native structures of proteins - a game.[2][3]

Foldit

Many of the same people who created Rosetta@home worked on the construction of Foldit. The public beta version was released in May 2008.[4]

Since 2008, the Foldit project has participated in Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiments, submitting its best solutions to targets based on unknown protein structures. CASP is an international experiment, which aims to assess existing methods of protein structure prediction, and highlight research that may be more productive toward solving protein structures.

In 2011, players of Foldit helped to decipher the crystal structure of the Mason-Pfizer monkey virus (M-PMV) retroviral protease, an AIDS-causing monkey virus. While the puzzle was available to play for a period of three weeks, players produced an accurate 3D model of the enzyme in just ten days. The problem of how to configure the structure of the enzyme had stumped scientists for 15 years.[5][6]

Since its inception, Foldit has attracted more than 46,000 users.[7]

Goals

Protein structure prediction is important in several fields of science, including bioinformatics, molecular biology, and medicine. Successful identification of the structural configuration of natural proteins enables scientists to study and understand proteins better. This can lead toward the creation of novel proteins by design, advancements in the treatment of diseases, and the development of solutions for other real-world problems, such as invasive species, waste, and pollution.

The process by which living beings create the primary structure of proteins, protein biosynthesis, is reasonably well understood, as is the means by which proteins are encoded as DNA. Determining how the primary structure of a protein turns into a functioning three-dimensional structure—how the molecule "folds"—is more difficult; the general process is known, but protein structure prediction is computationally demanding.

Methods

Similar to Rosetta@home, David Baker and his team of co-workers aim to use Foldit as a means of discovering native protein structures faster, through a combination of crowdsourcing and distributed computing. However, there is a greater emphasis on crowdsourcing and community collaboration with the Foldit project. Other methods, such as virtual interaction and gamification were added, creating a unique and innovative project environment with the potential to greatly assist the cause.

Virtual Interaction

Foldit attempts to apply the human brain's natural three-dimensional pattern matching and spatial reasoning abilities to help solve the problem of protein structure prediction. Current puzzles are based on well-understood proteins; by analysing the ways in which humans intuitively approach these puzzles, researchers hope to improve the algorithms employed by existing protein-folding software.

Foldit provides a series of tutorials in which the user manipulates simple protein-like structures and a periodically-updated set of puzzles based on real proteins. The application displays a graphical representation of the protein's structure which the user is able to manipulate with the aid of a set of tools.

Gamification

Rather than just building a useful science tool, the developers of Foldit focused on designing a program that adopted the concept of gamification; the aim was to make the program more appealing and engaging to a public audience, in order to attract more people to the cause of protein folding. This was especially true for those people that did not have a scientific education or background.

As the structure is modified, a "score" is calculated based on how well-folded the protein is, and a list of high scores for each puzzle is maintained. Foldit users may create and join groups, and share puzzle solutions with each other; a separate list of group high scores is maintained.

See also

References

  1. ^ Howard Hughes Medical Institute "Protein-folding game taps power of worldwide audience to solve difficult puzzles" Eurekalert!, August 4, 2010
  2. ^ Bourzac, Katherine. "Biologists Enlist Online Gamers" Technology Review, May 8, 2008
  3. ^ Bohannon, John. "Gamers Unravel the Secret Life of Protein" Wired (magazine), April 20, 2009
  4. ^ Hickey, Hannah. "Computer game's high score could earn the Nobel Prize in medicine" University of Washington, May 8, 2008
  5. ^ Attention: This template ({{cite doi}}) is deprecated. To cite the publication identified by doi:10.1038/nsmb.2119, please use {{cite journal}} (if it was published in a bona fide academic journal, otherwise {{cite report}} with |doi=10.1038/nsmb.2119 instead.
  6. ^ Praetorius, Dean. "Gamers Decode AIDS Protein That Stumped Researchers For 15 Years In Just 3 Weeks" The Huffington Post, September 19, 2011
  7. ^ "Alternative uses: The play’s the thing: What video-game technology can do in the real world", The Economist, 10 December, 2011

External links