January 17, 2022
Biochemistry Cumulative Exam
Topic: Protein structure, function, binding and computational design
- Bryan, Cassie M., Gabriel J. Rocklin, Matthew J. Bick, Alex Ford, Sonia Majri-Morrison, Ashley V. Kroll, Chad J. Miller, et al. “Computational Design of a Synthetic PD-1 Agonist.” Proceedings of the National Academy of Sciences 118, no. 29 (July 20, 2021): e2102164118. https://doi.org/10.1073/pnas.2102164118
It is highly recommended that you consult the references cited in the paper (and therein) to learn more about the background and methods employed.
Students may use the Bryan et al. paper listed under “Reading” during the exam. No other materials are permitted.
Learning goals. Be able to discuss:
- The biological function of PD-1 and background on the need for synthetic agonists
- The main experimental and computational methods used, including (but not limited to)
computational protein design using Rosetta; on overview of the “Motifgraft” and “Fold-From-Loops” protocols used in the paper
- yeast display and affinity maturation
- binding and activity assays
- Biophysical methods like CD and biolayer interferometry (BLI)
- The work’s main results and conclusions. Know what information is presented in each figure, and what conclusions the experimental data imply. (Example: Figure 2 presents a color-map of Shannon entropies – know what that is, and how to compute it)
- Knowledge of basic biochemical principles (protein structure, energetics, stability, folding, binding affinity, kinetics) and how they apply to this study.
If you are totally unfamiliar with Rosetta and computational protein design, David Baker (HHMI, Univ. Washington) has an introductory iBiology video seminar you should watch:
- Part 1: Introduction to Protein Design https://www.youtube.com/watch?v=0LetJMbu7uY
- Part 2: Part 2: Design of New Protein Functions https://www.youtube.com/watch?v=ZrAwWx7meTk
Post-CUME review party
I will host a Biochem CUME review party on Tuesday Jan 18 at 4 pm, in BE226. If you are interested and can’t make that time, let me know: firstname.lastname@example.org