Characterizing Osmolyte Interactions with Intrinsically Disordered Tau

Zheng Ji

Mentor: Dr. Priyanka Joshi, Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center.

Date/Time: December 10th, 2024 at 12:00pm.

Abstract: Neurodegenerative diseases like Alzheimer’s are marked by abnormal protein aggregation, such as tau amyloid filaments, which are closely linked to neuronal dysfunction. Tau, an intrinsically disordered protein (IDP), undergoes misfolding and aggregation through liquid-liquid phase separation (LLPS). While small molecules such as polyanions have been studied for their role in tau aggregation, the effects of osmolytes—small organic compounds that stabilize proteins and maintain cellular homeostasis—remain insufficiently understood.

This study uses computational approaches to investigate osmolyte-tau interactions, leveraging databases like HMDB, UniProt, PDB. Osmolytes will be selected based on their biochemical relevance and conservation across species. AlphaFold3 will model their interactions with tau. Seamdock and Molecular Dynamics with PLUMED will make and compare the predictions to functional and pathogenic tau conformations. The findings aim to reveal how osmolytes influence tau folding and misfolding, offering potential insights for therapeutic strategies against Alzheimer’s disease.