Design of a PPI Inhibitor to Treat AAV – UROP Spring Symposium 2021

Design of a PPI Inhibitor to Treat AAV

Alyssa Anderson


Pronouns: she/her/hers

Research Mentor(s): Yang Zhang, Professor
Research Mentor School/College/Department: Department of Computational Medicine & Bioinformatics, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 3 (1pm-1:50pm)
Breakout Room: Room 17
Presenter: 5

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Many diseases, such as ANCA-associated vasculitis (AAV), are caused by mutated proteins involved in protein-protein interactions (PPIs) that can be inhibited by designer proteins that would serve as small molecule inhibitors. In the case of AAV, the targeted interaction is between TNF-alpha and its associated TNFR1 receptor, which induces the activation of neutrophils in endothelial cells, causing inflammation in AAV patients. By designing a protein which will bind to TNF-alpha, its interaction with TNFR1 can be decreased, thus decreasing patient inflammation. UniDesign from the Zhang Lab was used to design de novo protein sequences from a PDB model of the TNF-alpha and TNFR1 interaction. The results were then analyzed by comparing the binding energy of the designer protein against the native sequence. These results are very promising in the development of protein design as a viable treatment method for rare diseases. This new protein could provide a novel type of treatment to AAV patients that would mitigate the use of glucocorticoids, a common anti-inflammatory agent with long-term side-effects such as increased risk for infections, heart disease, etc.

Authors: Alyssa Anderson, Xiaoqiang Huang
Research Method: Laboratory Research

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