Using Open-Source Bioinformatics and Visualization Tools to Explore the Structure and Function of SARS-CoV-2 Spike Protein

The relationship between protein structure and function is a foundational concept in undergraduate biochemistry. We find this theme is best presented with assignments that encourage exploration and analysis. Here, we share a series of four assignments that use open-source, online molecular visualization and bioinformatics tools to examine the interaction between the SARSCoV-2 spike protein and the ACE2 receptor. The interaction between these two proteins initiates SARS-CoV-2 infection of human host cells and is the cause of COVID-19. In assignment I, students identify sequences with homology to the SARSCoV-2 spike protein and use them to build a primary sequence alignment. Students make connections to a linked primary research article as an example of how scientists use molecular and phylogenetic analysis to explore the origins of a novel virus. Assignments II through IV teach students to use an online molecular visualization tool for analysis of secondary, tertiary, and quaternary structure. Emphasis is placed on identification of noncovalent interactions that stabilize the SARS-CoV-2 spike protein and mediate its interaction with ACE2. We assigned this project to upper-level undergraduate biochemistry students at a public university and liberal arts college. Students in our courses completed the project as individual homework assignments. However, we can easily envision implementation of this project during multiple in-class sessions or in a biochemistry laboratory using in-person or remote learning. We share this project as a resource for instructors who aim to teach protein structure and function using inquiry-based molecular visualization activities. Citation: Listenberger LL, Joiner CM, Terrell CR. 2022. Using open-source bioinformatics and visualization tools to explore the structure and function of SARS-CoV-2 spike protein. CourseSource. https://doi.org/10.24918/cs.2022.5 Editor: Charles Hauser, St. Edward’s University Received: 1/5/2021; Accepted: 9/9/2021; Published: 3/18/2022 Copyright: © 2022 Listenberger, Joiner, and Terrell. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. The images used in supporting materials (Supporting File S3: Molecular Modeling – Summative Assessments and Data from Student Responses) are from journals that use the Creative Commons Attribution License. We cite the original source for each figure. The primary image includes student generated data and a cartoon from Pixabay, an online repository of copyright free art. Conflict of Interest and Funding Statement: None of the authors has a financial, personal, or professional conflict of interest related to this work. Supporting Materials: Supporting Files S1. Molecular Modeling – BioMolViz Goals and Objectives; S2. Molecular Modeling – Assignments I-IV; S3. Molecular Modeling – Summative Assessments and Data from Student Responses; S4. Molecular Modeling – Answer Key (contact corresponding author for a copy); and S5. Molecular Modeling – Teaching Resources. *Correspondence to: University of Minnesota, Center for Learning Innovation, 111 S. Broadway, Rochester, MN, 55904, terre031@r.umn.edu. CourseSource | www.coursesource.org 2022 | Volume 09 1 Lesson