UC Santa Barbara

Protein oligomers play important roles in both pathological and physiological conditions. Abnormal protein oligomerization has been observed in over 50 human diseases, including Alzheimer's disease and ALS. Protein oligomers also form ion channels such as SARS-CoV Envelope protein and TRPV4, which are critical in both viral and human life cycles. Due to the multiple roles of protein oligomers, they are important therapeutic targets for small molecules. In this dissertation, I study the assembly of various proteins associated with neurodegenerative diseases (Aβ25-35 for Alzheimer's, TDP-43, G3BP1, and G3BP2a for ALS), as well as SARS-related peptides (SARS-CoV and SARS-CoV-2 Envelope protein fragments), and TRPV4, a protein involved in cholestatic liver disease itch. By using experimental techniques such as ion mobility mass spectrometry and molecular dynamics simulations, this study sheds light on the underlying mechanisms for protein oligomerization and the interactions between small molecules and peptide oligomers.