Design of novel proteins targeting the PD-1/PD-L1 pathway – UROP Spring Symposium 2021

Design of novel proteins targeting the PD-1/PD-L1 pathway

Alex Sheinberg


Pronouns: He/Him

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: 6

Event Link


The PPI being analyzed is PD-1 to PD-L1. Programmed cell death 1 (PD-1) is a protein involved in regulating the immune system’s T-cell induced apoptosis system by suppressing T-cells. Therefore, PD-1 suppresses and prevents cell apoptosis. PD-1 performs this function in unison with PD-L1 or Programmed Death Ligand 1. The suppression of T-cells can only occur when PD-1 is bound to PD-L1, therefore, this a very important protein-protein interaction. Because this PPI is highly involved in cell cycle regulation it is a common target of cancer treatments. One common cancer treatment is a drug that blocks PD-1 and prevents it from complexing with PD-L1. By hindering this PPI, T-cells’ ability to kill possibly cancerous cells is increased. Using an evolutionary-profile based approach program called UniDesign, 300 possible different peptide sequences were created for PD-1 while keeping PD-L1 the same. Although results have not been obtained we hope to show through the experimental analysis that the designed sequences will have a stronger binding affinity to PD-L1 than PD-1. This research is important because better understanding this PPI plays a large role in cancer treatment research.

Authors: Alex Sheinberg, Xiaoqiang Huang, Yang Zhang
Research Method: Laboratory Research

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