Shayaan's Research Blog

My research focuses on understanding how phosphorylation of nucleolin (NCL), a multifunctional RNA-binding protein, may influence protein interactions involved in the DNA damage response. Although nucleolin has been implicated in chromatin organization, ribosome biogenesis, and DNA repair, the molecular mechanisms underlying its role in DNA damage signaling are still not fully understood.

To investigate this, I use computational molecular modeling approaches to study how phosphorylation at specific nucleolin residues affects interactions with BRCT-domain proteins involved in DNA repair pathways, including BRCA1-associated complexes. My work primarily involves relative binding free energy simulations and structural analysis to compare phosphorylated and non-phosphorylated nucleolin peptides and evaluate how these modifications may alter binding behavior.

Current analyses focus on several cancer-relevant phosphorylation sites distributed throughout nucleolin, many of which are located outside of the canonical RNA-binding domains. Preliminary findings suggest that phosphorylation may play an important role in regulating nucleolin-mediated protein interactions rather than directly affecting RNA binding itself.

In parallel with the computational work, this project also incorporates experimental planning related to DNA damage assays and downstream validation studies. Overall, this research aims to better understand how post-translational modifications of nucleolin may contribute to DNA repair signaling and genome stability, with broader implications for cancer biology.