correspondence Introducing Foldit Education Mode

To the Editor — In its twelve years online, scored using the Rosetta force field2, with that walk the student through a standard Foldit has become a frequently used the players collaborating and competing to set of topics in biochemistry education teaching tool for biochemistry at the attain the best-scoring protein structure. (Fig. 1a), including atomic interactions, the college level, despite not providing premade The concept is that, if hundreds or hydrophobic effect, amino acids, primary content specifically for education. Here thousands of players all work to create a structure, secondary structure, tertiary we introduce Foldit Education Mode, protein structure, there is a higher chance structure, protein folding pathways and in which students proceed through a that one of them may find the correct fold. ligand binding. Many of the puzzles start by self-guided tutorial of standard concepts The interactive nature of Foldit and its allowing the student to explore the puzzle in protein biochemistry via a series of accessibility to non-scientist audiences as a sandbox, thus becoming familiar interactive three-dimensional biochemistry quickly attracted the interest of educators3–6, with it before starting the tutorial. In each puzzles. Education Mode could be used despite Foldit not providing material that is puzzle, students click through a tutorial independently or as a central component explicitly tailored for science education. We on the topic that guides them through the of a science class. With many classrooms have recently introduced Custom Contests7, conceptual basis of the puzzle (Fig. 1b). staying in remote mode this autumn, Foldit a feature that allows educators to create, Then, students solve the puzzle by achieving Education Mode offers a unique and free administer and grade their own Foldit a prespecified Foldit score. In many levels, online option for classes worldwide and is puzzles to fit their curriculum, but Custom this score is modified to provide a bonus available for download at our new educator’s Contests do not provide pre-made content that rewards specific outcomes, such as page: https://fold.it/educator. to teach standard topics in biochemistry. rewarding the creation of hydrogen bonds Foldit is a free citizen science The need for online learning in a puzzle that judges β-sheet formation. biochemistry computer game1. In the most opportunities has vastly increased in recent Along the way, students learn Foldit tools basic Foldit puzzles, players try to fold a months due to the COVID-19 pandemic, that will allow them to complete more protein into its proper three-dimensional and we have responded by creating Foldit advanced puzzles. These are a mixture of structure, starting from an unfolded peptide. Education Mode. Currently, Education protein design puzzles (Fig. 1c), folding The players’ structures are immediately Mode consists of 29 puzzles split into 9 tiers puzzles (Fig. 1d) and sequence alignment

ab d

Non-covalent interactions and sidechains (5 puzzles)

Primary structure (3 puzzles)

Foldit Automating tools (2 puzzles)

Secondary structure c e (8 puzzles)

Sequence defines fold (5 puzzles)

Tertiary structure (3 puzzles)

Folding and binding (3 puzzles)

Fig. 1 | Foldit Education Mode. a, A flowchart depicting the current topics and number of puzzles within Foldit Education Mode. b, Wiggle puzzle, showing a tutorial bubble example. Students click back or next to proceed through the tutorials within each puzzle. c, An example of a protein design puzzle, “Primary Structure,” in which students are asked to choose amino acids that optimize the protein’s stability. d, An example of a protein folding puzzle, “Tertiary Structure,” in which students are given a protein with preformed secondary structure and are asked to fold it into a stable tertiary structure. e, An example of a sequence alignment puzzle. In this puzzle, “Alignin’ Sequences,” students are asked to align the sequence of a protein to that of a protein of known structure to enable structural threading.

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puzzles (Fig. 1e), which are used to teach written assignments (for example, the 3Department of Chemistry & Biochemistry and the different topics. “Primary Structure” and “Tertiary Structure” Knoebel Institute for Healthy Aging, University of Although the tutorial is self-guided puzzles), instructors may consider skipping Denver, Denver, CO, USA. and can be used by anyone interested in the version in Education Mode and ✉e-mail: [email protected] learning biochemistry, it was specifically downloading a Custom Contest version created for class use. Instructors can of the puzzle instead. Moreover, we note Published online: 17 August 2020 choose to skip puzzles as needed and can that Education Mode is a different release https://doi.org/10.1038/s41594-020-0485-6 supplement with puzzles from the standard from standard Foldit, and playing standard Foldit tutorials if desired. Several of the science puzzles will require switching to the References puzzles have already been used in class, with main release of Foldit. 1. Cooper, S. et al. Nature 466, 756–760 (2010). accompanying written assignments that can Finally, we are making this 2. Alford, R. F. et al. J. Chem. Teory Comput. 13, 3031–3048 (2017). 3. Farley, P. C. Biochem. Mol. Biol. Educ. 41, 56–57 (2013). be downloaded at our educator’s webpage announcement before Education Mode has 4. Franco, J. J. Chem. Educ. 89, 1543–1546 (2012). (https://fold.it/educator). Students are undergone stringent educational testing, due 5. Stockman, B. J. et al. J. Chem. Educ. 91, 451–454 (2014). also able to use the in-game chat function to the urgent need for such tools right now. 6. Achterman, R. R. J. Microbiol. Biol. Educ. 20, 20.3.63 (2019). to discuss their puzzles in real time We welcome all feedback on how to improve 7. Dsilva, L. et al. Biochem. Mol. Biol. Educ. 47, 133–139 (2019). with other students in their class or the Education Mode. ❐ with their instructor. Acknowledgements Some important notes: students are Josh Aaron Miller 1, Firas Khatib 2, We thank Kimberly Cortes, Ashley Vater and 3 1 Irina Makarevitch for their prerelease input and currently unable to turn in their puzzles Haley Hammond , Seth Cooper and Jeff Flatten, Zoran Popović, Henry Solberg, Rocco Moretti, 3 ✉ for grading through the Foldit client, and Scott Horowitz David Baker and Jens Meiler for aid with Foldit support. the instructor does not have access to their 1Khoury College of Computer Sciences, Northeastern This work was supported by NIH R00 GM120388. solutions. These features are available University, Boston, MA, USA. 2Department of in Custom Contests; thus, for larger and Computer and Information Science, University of Competing interests more involved puzzles with accompanying Massachusetts Dartmouth, Dartmouth, MA, USA. The authors declare no competing interests.

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