Using the Computer Game “FoldIt” to Entice Students to Explore External Representations of Protein Structure in a Biochemistry Course for Nonmajors


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This article describes a novel approach to teaching novice Biochemistry students visual literacy skills and understanding of some aspects of protein structure using the internet resource FoldIt and a worksheet based on selected Introductory Puzzles from this computer game. In responding to a questionnaire, students indicated that they (94%) enjoyed playing the game and furthermore, they indicated that they (100%) perceived an improvement in their understanding of protein structure as a result. Instructor observation of the students using the game together with the worksheet corroborated the results of the student perception survey. © 2012 by The International Union of Biochemistry and Molecular Biology, 41(1):56–57, 2013

It is essential that students studying biochemistry learn to use external representations of molecules and molecular interactions, that is, they become “visually literate” [1]. The best strategy for teaching visual literacy is to have students work individually through a set of questions relating to specific external representations and, where intrinsic student motivation is low, to require submission of their answers [2]. Various materials are available for teaching visual literacy [3], but they are not particularly suitable for students at the novice end of the spectrum.

FoldIt is a computer game that was designed to use human intuition, in combination with the Rosetta algorithms, to predict protein structure [4, 5]. FoldIt players can use the deterministic Rosetta algorithms (although they are not described as such in the game) and other tools (including those that allow alignments, insertions, deletions, and sequence substitutions) [5-7], but human decision making replaces the stochastic Rosetta algorithms [4], and players can work cooperatively. In September 2011, FoldIt made headline news [8, 9] with the publication of the crystal structure of the Mason-Pfizer monkey virus retroviral proteinase determined using molecular replacement methods based on structural models generated by FoldIt players. The player-generated models were key to successful molecular replacement, and the contribution of two groups of players, in particular, was recognized by inclusion of their group names in the list of authors [5]. The general public interest in this story, as signaled by the appearance of articles in the press, suggested that it might appeal to students, particularly those for whom biochemistry is not their primary focus.

At the Faculty of Agriculture, Andalas University, students taking the Agro-ecotechnology major have the option of studying a Plant Biochemistry paper in their sixth semester. These students' prior exposure to external representations of molecules consists almost entirely of 2D structural formulae and schematic drawings. In the 2010/2011 academic year, students were given the opportunity to explore a protein's structure using the interactive molecular visualization software Jmol [10], but it did not engage their interest and proved too difficult for the one student who did attempt it. In the following year, the students (nine females and eight males) were introduced to the game FoldIt.

During the practical class in the first week of semester, students downloaded the game software, so their laptops would be ready when required later in the semester, but students immediately began trying it out and engaging with the game. This was not the case with other resources they obtained at the same time. In a student perception survey conducted at the end of the semester, 94% of students responded that the game was “asik dimainkan” (fun to play) and 47% stated that they had played the game outside of class time (range: 3–11 times; median and mean: five and six times, respectively). Of those who played outside class time, 75% were females. The most common primary reason for not playing outside of class time (44% of students in this category) was tidak ada waktu, terlalu sibuk dengan kegiatan lain (not enough time, too busy with other things), and only one student in this category chose tidak tertarik dengan mainan FoldIt (not interested in the game) as the main reason for not playing outside class time. These observations suggest that students were enticed by the game to explore visual representations of protein structure in their own time. This immediate and sustained engagement is achieved by a multilayered reward structure common to successful games [4].

The game itself consists of Introductory Puzzles and Science Puzzles. These puzzles present players with manipulatable images (external representations) of various polypeptides. Because FoldIt is written in English and many Indonesian students are more comfortable studying in their own language, a set of instructions was written in Indonesian (html format) to guide students through the Introductory Puzzles while, at the same time, asking them to think more deeply than required to simply complete the puzzle. The instructions cover all eight levels of Introductory Puzzles, but the questions focus on selected puzzles from the first four levels. These questions were then incorporated into a worksheet (an English language version is available as Supporting Information) that addresses at least four of the eight components of visual literacy defined by Schönborn and Anderson [3], namely, decoding an external representation, understanding an external representation's usefulness, as well as translating horizontally and vertically between different external representations. To some extent, FoldIt alone also addresses two further components, namely, visualization of relative size and problem solving using an external representation.

In class, the symbols used in FoldIt to represent the protein backbone and amino acid side chains are explained to students who subsequently practice decoding the symbols themselves as they identify amino acid side chains and primary/secondary structural elements in different puzzles. In the external representations used in FoldIt, the N- and C-termini are not identifiable, and two worksheet questions require students to recognize this limitation. To assist with translation between the FoldIt external representations and the 2D structural formulae these students are more familiar with, the Indonesian html instructions include a link to a page of 2D amino acid structural formulae.

In the end of semester student perception survey, not only did many students respond that the game was fun to play but all the students (100%) consistently responded that their understanding of protein structure was improved as a result of using the game. The student's perceived improvement in understanding was consistent with instructor observation of the students using the combination of worksheet and game in class. Both student questions and student–student interactions demonstrated an improved visual literacy and understanding of protein structure. In an attempt to quantify the games' usefulness, the mean marks obtained by students in written assessment in the 2010/2011 and 2011/2012 academic years were compared. In 2010/2011, the students were taught by lecture and tutorial, whereas in 2011/2012, the game was included along with the lectures and tutorials. No statistically significant difference was found; however, the game was only part of the lecture/tutorial material used in this course, both classes were small (8 and 17 students, respectively), and the assessment had not been written to assess the effectiveness of the game per se. In conclusion, both student perceptions and instructor observations suggest that using selected Introductory Puzzles from the internet resource FoldIt, in conjunction with the worksheet described here, is a novel and helpful way of teaching visual literacy and aspects of protein structure to novice biochemistry students who require some form of extrinsic motivation.