Combining iCn3D and NextStrain to create a novel undergraduate research experience around SARS-CoV-2 variants and commercial antibodies

Undergraduate research experiences are increasingly important in biology education with efforts underway to provide more projects by embedded them in a course. The shift to online learning at the beginning of the pandemic presented a challenge. How could biology instructors provide research experiences to students who were unable to attend in-person labs? During the 2021 ISMB (Intelligent Systems for Molecular Biology) iCn3D Hackathon–Collaborative Tools for Protein Analysis–we learned about new capabilities in iCn3D for analyzing the interactions between amino acids in the paratopes of antibodies with amino acids in the epitopes of antigens and predicting the effects of mutations on binding. Additionally, new sequence alignment tools in iCn3D support aligning protein sequences with sequences in structure models. We used these methods to create a new undergraduate research project, that students could perform online as part of a course, by combining the use of new features in iCn3D with analysis tools in NextStrain, and a data set of anti-SARS-CoV-2 antibodies. We present results from an example project to illustrate how students would investigate the likelihood of SARS-CoV-2 variants escaping from commercial antibodies and use chemical interaction data to support their hypotheses. We also demonstrate that online tools (iCn3D, NextStrain, and the NCBI databases) can be used to carry out the necessary steps and that this work satisfies the requirements for course-based undergraduate research. This project reinforces major concepts in undergraduate biology–evolution and the relationship between the sequence of a protein, its three-dimensional structure, and its function.