An assessment was developed using entries from the macromolecular Crystallographic Information File that was given to students in an upper level bioinformatics class at the end of the semester during a 2½ hour time period. Although all students completed the same questions, they were assessed on an individual protein they had worked on during the semester in the situated learning of the classroom as they completed computer‐based tutorials and exercises using internet sources. The students' difficulties with the external representation of their protein were: not following directions, not understanding how to use the computational software, or a lack of knowledge about their protein. The students also were required to answer questions that required biochemical knowledge. The difficulties they experienced during the assessment can be attributed to factors, such as, their reasoning ability, understanding of the concepts, and the external representations of their protein. © 2018 International Union of Biochemistry and Molecular Biology, 46(6):634–643, 2018.