engagement and scientific relevance. The driving example is Foldit, a game for scientific discovery in biochemistry. We describe the architecture of the game. The architecture is flexible and able to coevolve, along with the game’s players, to improve as a tool. We discuss the teaching and reward structures in the game, intended to appeal to a wide variety of players, regardless of biochemistry background.
A scientific discovery game translates a class of computationally difficult scientific problems into puzzles, and provides a game-like mechanism for non-scientist players to help solve these problems. Many traditional aspects of game design apply to scientific discovery games, including the design of introductory levels to draw newcomers and explain game mechanics, the use of a client-server architecture for competition and collaboration, and the requirement that the game be fun. However, unlike games whose goal is entertainment or education, scientific discovery games introduce a unique challenge: enabling non-scientist natural problem solvers to advance a specific scientific domain. This challenge influences all aspects of the game design. First, visualization and graphics need to promote human ability to see complex solutions and convey accurate scientific information while remaining accessible to beginners. Second, interaction design must optimize for natural interactions suitable for the human exploration process, while still respecting scientific constraints. Finally, the scoring mechanism needs to be informative enough to promote multiple human strategies, while remaining true to the latest models of the underlying scientific phenomenon. Perhaps the most distinguishing feature and the greatest difficulty of design for this type of game is that the solution to the scientific problem, and thus the solution to the corresponding puzzles, is unknown. Since we do not know the solution a priori, we cannot design the game with specific solutions in mind.
Figure 3.1 Foldit webpage. The front page shows recent news about the game, the top players and groups for the current puzzles, and allows the player to log in.
To explore this space, we focused on human ability to reason about 3D structures and on the biochemistry domain, where many problems tend to be structural. We developed Foldit, a biochemical discovery game. In this chapter, we discuss the framework for Foldit’s design, with emphasis on the game’s initial focus on protein structure prediction—determining a protein’s shape given its sequence of constituent amino acids. Protein structure prediction involves finding favorable interactions that form when the protein’s chemical groups come into contact—essentially a 3D jigsaw puzzle. We believe that humans’ innate spatial reasoning ability makes it possible for non-scientists to make useful contributions to this problem. We leverage scientists’ knowledge to shape the rules of the game, thus enabling a much larger pool of non-scientists to make discoveries within this framework.
The webpage for Foldit is located at http://fold.it. The front page is shown in Figure 3.1. Foldit was publicly released in May 2008. During the first two years following release, we ran roughly 600 structure prediction puzzles and had over 57,000 players from a wide variety of backgrounds participate.
The rest of this chapter describes our experience designing Foldit, with a special emphasis on the unique challenges posed by making biochemistry problems accessible to anyone. The creation of Foldit was a challenging and multidisciplinary project, drawing together computer science, art, game design and biochemistry. Moreover, we did not know ahead of time which parts of the problem players would be best at solving, or which in-game manipulation tools they would use most effectively. The only way to find out was to have people play Foldit. In order to deal with these and other uncertainties, we took an iterative approach both before and after releasing the game to the public. We have continually evolved the gameplay in response to massive gameplay traces, player feedback and scientists’ analysis, and continue even now with this iterative process as we add features and expand the set of biochemical problems to which the Foldit community can contribute.
Games are often designed with an iterative approach, which involves designing, testing, and evaluating repeatedly until the player’s experience meets some criteria [Fullerton 2008 ]. For most games, the main criterion for the player’s experience is simply to have fun. Player feedback and playtesting are an integral part of the process, and there are a number of methods of gathering and incorporating this information from players [Ambinder 2009 ]. We have also continued the design process after the game’s release, to incorporate data gathered from the players in a continual process of evolutionary redesigning [Kennerly 2003 ]. Our work differs from the standard iterative approach in that the game design space is constrained to conform with existing physical models, we include the input of scientists in the evaluation of the game, and we include the long-term coevolution of the players and game in the design.
3.2 Biochemistry Background
Here we provide some background on biochemistry and proteins that will be used throughout the rest of this work.
DNA, a cellular chemical perhaps more widely recognized than proteins, derives its entire purpose in encoding protein sequences. Proteins are coded for by DNA, and are created in the cell as a long chain of amino acids. A protein’s amino acid sequence is known as its primary structure. There are twenty different types of amino acids. Regardless of type, some of atoms making up the amino acid will be the same; these are connected together and form the protein’s backbone. However, the remaining atoms are different for each type; these extend outward from the backbone and are called sidechains. The atoms that make up the sidechains divide the amino acids into two main groups: hydrophobic, which prefer to be buried on the interior away from water; and hydrophilic, which prefer to be exposed on the exterior near water. These preferences impact how the protein folds. As the amino acids are connected together, the protein begins to fold up; after the amino acids join together, they are often called residues. Local characteristics of the fold are referred to as secondary structure. These include: helices, which are tightly coiled; sheets, which are extended straight; and loops, which are everything else. The positions of the atoms making up a folded protein is its tertiary structure; the tertiary structure taken in nature is a native structure. The native structure is one that is lowest in free energy—it has the most favorable set of chemical interactions. It is well known that sequence determines structure [Anfinsen 1973 ]. In this book, the term sequence will refer to a protein’s primary structure, and structure will refer to its tertiary structure, unless otherwise specified.
3.3 Framework Description
3.3.1 Architecture
Herewegiveanoverview of the architecture of Foldit, which can be seen at a high level in Figure 3.2. Foldit uses a client-server architecture. Players must create an account and download the game in order to play. Thegamethen communicates with a central server to send information about the local player and get information about other players.
Scientists post problems to the server; in the case of Foldit, these are protein structures for which the players are meant to find the native structures. An initial protein structure is associated with metadata such as a title and description, and parameterization such as which energy function terms to use. We call these puzzles, and they are posted on the server for a fixed amount of time (usually a week). While a puzzle is active, players can download it and interactively reshape the protein to try to achieve the best score. This often requires significant changes to the puzzle structures, which are given in various partially-folded states, and in some cases need to be completely refolded from a straight line. Players’ structures, or solutions, are reported back to the server, and players are ranked against other players who are playing
