Foldit

Foldit

Screenshot of the Foldit application showing a folding puzzle in progress
Developer(s)	University of Washington (Center for Game Science, Department of Biochemistry)
Initial release	May 8, 2008
Development status	Active (Perpetual beta)
Operating system	Cross-platform (Microsoft Windows, Mac OS X, Linux)
Size	~391.9 MB
Available in	English, Russian, French (6 others)
Type	Puzzle video game, Protein folding
License	Freeware for academic and non-profit use
Website	http://fold.it/

Foldit is an online puzzle video game about protein folding. It is part of an experimental research project developed by the University of Washington's Center for Game Science in collaboration with the UW Department of Biochemistry. The objective of Foldit is to fold the structures of selected proteins as well as possible, using tools provided in the game. The highest scoring solutions are analysed by researchers, who determine whether or not there is a native structural configuration (native state) that can be applied to relevant proteins in the real world. Scientists can then use these solutions to target and eradicate diseases and create biological innovations. A 2010 paper in the science journal Nature credited Foldit's 57,000 players with providing useful results that matched or outperformed algorithmically computed solutions.^[1]

History

Rosetta

Prof. David Baker, a protein research scientist at the University of Washington, founded the Foldit project. Seth Cooper was the lead game designer. Before starting the project, Baker and his laboratory coworkers relied on another research project, Rosetta, to predict the native structures of various proteins using special computer protein structure prediction algorithms. Rosetta was eventually extended to utilize the power of distributed computing: The Rosetta@home program was made available for public download, and displayed its protein-folding progress as a screensaver. Its results were sent to a central server for verification.^[2]

Some Rosetta@home users became frustrated when they saw ways of solving protein structures themselves but could not interact with the program. Hoping that humans could improve the computers' attempts to solve protein structures, Baker approached David Salesin and Zoran Popović, computer science professors at the same university, to help conceptualize and build an interactive program—a game—that would appeal to the public and help efforts to find native protein structures.^[3][4][5]

Foldit

Many of the same people who created Rosetta@home worked on Foldit. The public beta version was released in May 2008^[6] and has 240,000 registered players.^[7]

Since 2008, Foldit 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 program to assess methods of protein structure prediction and identify those that are most productive.

Goals

Protein structure prediction is important in several fields of science, including bioinformatics, molecular biology and medicine. Identifying natural proteins' structural configurations enables scientists to understand them better. This can lead to the creation of novel proteins by design, advancements in the treatment of disease, and 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. However, determining how a particular protein's primary structure becomes a functioning three-dimensional structure—how the molecule "folds"—is more difficult. The general process is understood, but predicting a protein's eventual, functioning structure is computationally demanding.

Methods

Similarly to Rosetta@home, Foldit is a means of discovering native protein structures faster through distributed computing. However, Foldit has a greater emphasis on crowdsourcing and community collaboration. Foldit's virtual interaction and gamification create a unique and innovative environment with the potential to greatly advance protein folding research.

Virtual Interaction

Foldit attempts to apply the human brain's 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 how humans intuitively approach these puzzles, researchers hope to improve the algorithms used by protein-folding software.

Foldit includes a series of tutorials where users manipulate simple protein-like structures and a periodically updated set of puzzles based on real proteins. It shows a graphical representation of each protein which users can manipulate using a set of tools.

Gamification

Foldit's developers wanted to attract as many people as possible to the cause of protein folding—so rather than just building a useful science tool, they used gamification (the inclusion of gaming elements) to make Foldit appealing and engaging to the general public.

As a protein 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; a separate list of group high scores is maintained.

Accomplishments

• A 2010 paper in science journal Nature credited Foldit's 57,000 players with providing useful results that matched or outperformed algorithmically computed solutions.^[1]

• In 2011, Foldit players helped decipher the crystal structure of the Mason-Pfizer monkey virus (M-PMV) retroviral protease, an AIDS-causing monkey virus, a scientific problem that had been unsolved for 15 years. Although the puzzle was available for three weeks, players produced an accurate 3D model of the enzyme in just ten days.^[8][9]

• In January, 2012, Scientific American reported that Foldit gamers achieved the first crowdsourced redesign of a protein,^[7] an enzyme that catalysed the Diels-Alder reactions widely used in synthetic chemistry. A team including David Baker in the Center for Game Science at University of Washington in Seattle computationally designed the enzyme from scratch but found its potency needed improvement. Foldit players reengineered the enzyme by adding 13 amino acids, increasing its activity by more than 18 times.^[7][10]

Future development

Foldit's toolbox is primarily for the design of protein molecules. The game's creator announced the plan to add, by 2013, the chemical building blocks of organic subcomponents to enable players to design small molecules.^[11]

See also

References

External links

• Foldit project homepage
• Official Foldit wiki
• Folding@home homepage
• Rosetta@home homepage
• The Baker Laboratory homepage