Assessing Trans Activation of Ddi2 by Ubiquitin using Computational Modeling

Author

• Vineel Vanga, Mississippi State UniversityFollow
• Galen Andrew Collins, Mississippi State UniversityFollow

ORCID

Vanga: https://orcid.org/0009-0007-0901-9647

Degree

Bachelor of Science (B.S.) in Biochemistry & Molecular Biology

Major(s)

Biochemistry & Molecular Biology

Document Type

Temporary Embargo for Patent/Proprietary Reasons then Open Access

Abstract

The Ubiquitin Proteasome Pathway (UPP) critically regulates cellular homeostasis by degrading excess or damaged proteins. It does so by attaching the protein ubiquitin to target substrates, then degrading them via the 26S proteasome. A crucial but understudied player in this pathway is DNA damage-inducible protein 2 (Ddi2). Ddi2 has two currently known functions: it can deliver ubiquitylated proteins to proteasomes for degradation, and it can itself cleave proteins using its retroviral protease domain. Ddi2 also mediates cancer cells’ ability to escape immune detection. Previous studies showed that retroviral protease inhibitors designed for HIV increase MHC-I levels on the cell surface, thereby restoring immune recognition of cancer cells. Our model is that Ddi2 somehow facilitates the degradation of MHC-I molecules. We are exploring how Ddi2 is regulated by binding to ubiquitylated conjugates using computational modeling. We are testing if Ddi2 is allosterically activated by ubiquitylation using AlphaFold3 (DeepMind) and ChimeraX (UCSF).

Date Defended

4-27-2026

Funding Source

CALS Undergraduate Research Scholars Program

Thesis Director

Dr. Galen Collins

Second Committee Member

Dr. Aswathy Rai

Third Committee Member

Dr. Danielle Wylie

Recommended Citation

Vanga, Vineel and Collins, Galen Andrew, "Assessing Trans Activation of Ddi2 by Ubiquitin using Computational Modeling" (2026). Honors Theses. 215.
https://scholarsjunction.msstate.edu/honorstheses/215

Rights Statement

© 2026 Vineel Vanga. This thesis is made available under a Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) license. It may be shared with proper attribution but may not be altered or used for commercial purposes.