De novo Design of Protein Based HER2 Inhibitor – UROP Spring Symposium 2021

De novo Design of Protein Based HER2 Inhibitor

Anusha Tekumulla

Anusha Tekumulla

Pronouns: she/her

Research Mentor(s): Jaie Woodard, Postdoctoral Fellow
Research Mentor School/College/Department: Computational Medicine and Bioinformatics, Michigan Medicine
Presentation Date: Thursday, April 22, 2021
Session: Session 1 (10am-10:50am)
Breakout Room: Room 14
Presenter: 4

Event Link


Protein function is determined by protein structure, which is in turn determined by the corresponding protein sequence. Because we understand how a protein adopts a particular structure, it is possible to redefine the function of a protein by working backward from the desired structure to the sequence. De novo protein design is used to design new protein structures from scratch based on loose constraints supplied by the user. The ultimate goal is to develop inhibitors to the HER2 receptor to prevent ERK and AKT cancer pathways from being activated. The hope in doing this is to prevent unnecessary cell signals from replicating that ultimately lead to breast cancer. To design mini protein inhibitors, we will first extract the native interfaces from experimentally solved structures of known HER2 binding proteins. The next step will be determining the proposed topologies for the designs. These topologies will be fed into FoldDesign to generate the inhibitor structures. The resulting scaffolds will then be fed into EvoDesign to design sequences for these structures. The results can be validated in either a wet lab or using computations. The designs will be tested for their binding affinity and folding stability. We expect to be able to design an inhibitor to HER2 with high affinity and demonstrate stability with computations.

Authors: Anusha Tekumulla, Robin Pearce
Research Method: Computer Programming

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