The Biochemistry Authentic Scientific Inquiry Lab (BASIL) uses a combined computational and wet lab approach to study proteins of known structure but unknown function. This course-based undergraduate research experience (CURE) allows a large number of students to gain skills often learned only in the traditional one-on-one mentor-student research model by bringing a research project into the undergraduate teaching lab. The major goal of the BASIL curriculum is to teach students to think like scientists while studying the relationship between structure and function in proteins. The curricular materials are available free-of-charge at basilbiochem.org. There are over 4000 experimentally determined protein structures of unknown function in the Protein Data Bank (PDB), and this number grows if computationally-determined structures are included. In the BASIL curriculum, students use sequence alignment, structure alignment, and molecular docking to study selected structures of unknown function with the goal of identifying enzymes. Students then produce the target enzymes in the lab using standard wet-lab biochemistry techniques for expression and purification. They can then perform activity assays with model substrates selected from their docking studies. One of the most difficult parts of the curriculum is selecting appropriate substrates for testing the predicted enzyme functions and identifying appropriate experimental conditions for assays. Since 2016, we have studied more than 20 protein structures of unknown function using the BASIL curriculum, and we have had varied success verifying the functions using enzyme assays. Among the structures studied, we have identified hydrolase, lyase, and oxidoreductase activity. This project is supported in part by NSF IUSE 2141908.
Koeppe et al. (Sun,) studied this question.