What is Foldit?
Foldit is a game about folding proteins to save the world! No, seriously – in Foldit, you as the player create stable configurations of amino acids that adopt useful real-world structures and properties, like proteins that can break down non-biodegradable material or fight contagious diseases. As mentioned on the website, notable players can receive accreditation for their work: “Discoveries made in the game are published in peer-reviewed research journals and Foldit players are always credited for their contributions.”¹
The emphasis on academic acknowledgement makes sense, as Foldit is an experimental research project founded by Professor David Baker, a protein research scientist at the University of Washington.
How Does It W̶o̶r̶k̶ Play?
In Foldit, players solve a series of puzzles related to protein design using molecular visualization software. But unlike other molecular viewers, like PyMOL, Foldit opts for a gamified, accessible approach to protein discovery, complete with tooltips and tutorials that teach even the layman about the biochemistry behind proteins and how to design them.
To do this, the game starts off by asking the player to maximize a “score,” which is initially a somewhat nebulous metric. However, the game slowly shows the player how to raise their score through a series of do’s and don’ts (e.g. do orient the hydrophobic amino acid within the protein away from water, and don’t place these backbone structures close together).
Although the game never tells the player they are trying to minimize the potential energy of the system, and that this potential energy is the quantification of their score, the player gains an intuitive understanding of how to do so! Eventually, the player is given the option of changing the individual amino acids to get the structure to fold in a particular way – this is exactly the kind of work that real protein researchers do!
Breaking It M-DAOn
- Mechanics
- Drag – Players can use their mouse to move, orient, or twist amino acids, beta sheets, alpha helices, and other doodads.
- Wiggle/Shake – Players can press a button to automatically allow the computer to find the local minimum potential energy of the current system by applying realistic physical interactions to the current system, like electromagnetic repulsions and attractions. This does not automatically solve the puzzle for the player, as the player still has to find the global minimum.
- Mutate – Players can choose to change the specific amino acid in a chain (e.g. transforming a cysteine to serine).
- Dynamics
- Experimentation – Players soon try to throw things at a wall to see what sticks: “If I drag the molecule this way, will it increase my score? What if I change this amino acid to something hydrophilic?”
- Aesthetics
- Challenge – Many non-trivial problems of various difficulties on the Foldit website are open problems, and serve as an obstacle course for the players to overcome.
- Discovery – On the puzzles page of the Foldit website, there are mentions of many protein structures in official papers that could use some improvements. For instance, the description for Puzzle 2499 on the website states: “The structure of this protein has already been solved and published, but close inspection suggests that there are some problems with the published solution. We’d like to see if Foldit players can use the same electron density data to reconstruct a better model.”³ Here, Foldit players constantly venture into uncharted territory.
- Outcomes
- Education – Players not only learn about the real-world physical interactions of amino acids and how they form proteins, but also why protein design is important for solving the world’s problems, and how they can make a difference.
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¹https://fold.it/about_foldit
²https://dataphys.org/list/proteine-visualizations/
³https://fold.it/puzzles
