Investigating the Effects of Small Peptides on Amyloid Aggregation

Abstract

Amyloids, a class of protein aggregates, are highly stable elongated fibril structures. They areassociated with numerous diseases, such as Alzheimer’s, Parkinson’s, and type II diabetes. Following the COVID-19 pandemic, there have been numerous cases of individuals suffering with Long-COVID, whose symptoms overlap with common neurodegenerative and amyloid associated diseases. To explore the potential interactions between SARS-CoV-2 and amyloid proteins, two amyloidogenic protein fragments from SARS-CoV-2 were investigated with amylin, the amyloid protein associated with type II diabetes, and a-synuclein, associated with Parkinson’s. These investigations were performed utilizing all-atomistic molecular dynamics simulations in explicit solvent. Additionally, presented in this dissertation is research performed to identify and evaluate the effect of novel D-retro-inverso (DRI) peptides on mouse serum amyloid A3 (SAA3) fibril stability via virtual screening and molecular dynamics simulations.