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Biochemistry curricula present a particular challenge to undergraduate students with abstract concepts which can lead to misconceptions that impede learning. In particular, these students have difficulty understanding enzyme structure and function concepts. Targeted learning activities and three‐dimensional (3D) physical models are proposed to help students challenge these misconceptions and increase conceptual understanding. Here we assessed such pedagogical tools using the Enzyme‐Substrate Interactions Concept Inventory (ESICI) to measure (mis)conceptual changes from Pre‐ to Post‐ time points in a single semester undergraduate biochemistry course. A Control group of students engaged with the active learning activities without the 3D physical models and students in the Intervention group utilized these activities with the 3D physical models. At the Post‐ time point both groups had higher, yet similar ESICI scores of the same magnitude as the highest scoring group from the national sample. Concomitantly, many misconception markers decreased compared to the national sample, although some of these differed between the Control and Intervention groups. Based on this assessment, both pedagogical approaches successfully increased conceptual understanding and targeted many of the misconceptions measured by the ESICI, however, several misconceptions persisted. Surprisingly, the students who used the 3D physical models did not demonstrate a further decrease in the misconception markers. Additionally, psychometric evaluation of the ESICI with our sample recommends the revision of several questions to improve the validity of this assessment. We also offer suggestions to improve instruction and pedagogical tools with further avenues for research on learning.

Introductory biochemistry courses are often challenging for students because they require the integration of chemistry, biology, physics, math, and physiology knowledge and frameworks to understand and apply a large body of knowledge. This can be complicated by students' persistent misconceptions of fundamental concepts and lack of fluency with the extensive visual and symbolic literacy used in biochemistry. Card sorting tasks and game‐based activities have been used to reveal insights into how students are assimilating, organizing, and structuring disciplinary knowledge, and how they are progressing along a continuum from disciplinary novice to expert. In this study, game‐based activities and card sorting tasks were used to promote and evaluate students' understanding of fundamental structure–function relationships in biochemistry. Our results suggest that while many markers of expertise increased for both the control and intervention groups over the course of the semester, students involved in the intervention activities tended to move further towards expert‐like sorting. This indicates that intentional visual literacy game‐based activities have the ability to build underdeveloped skills in undergraduate students.