Publication Date
Spring 2024
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
Advisor
Gianmarc Grazioli; Madalyn Radlauer; Nicholas Esker
Abstract
Amyloid fibrils are locally ordered protein aggregates characterized by a filamentous morphology held together by a hydrogen bonding motif known as cross-β structure whereby hydrogen bonds form between backbone amide bond moieties across separate protein segments. The most notable medical significance of amyloid fibrils is their central role in the etiology of Alzheimer’s disease, type 2 diabetes, and other human diseases. Although amyloid fibrils have been studied extensively, the mechanism of their formation is still not fully understood. X-ray crystallography is a leading experimental technique for resolving amyloid fibril structures from crystallized proteins; however, inherent limitations leave open the possibility that crystal structures generated under experimental conditions may not be representative of amyloid fibril structures formed under in vivo conditions. Here we used molecular dynamics (MD) simulations to study select mechanical properties of an amyloid fibril constructed from a crystal unit cell that was measured using x-ray crystallography and reported to the Protein Data Bank (PDB) as being the structure of a protein fibril formed by segments of the insulin chain B (residues 11-17). Specifically, Steered Molecular Dynamics (SMD) was used to apply artificial forces to insulin fibrils to the point of breakage, while maintaining experimentally similar conditions to AFM experiments. Subsequent stress-strain curves were then generated and compared to analogous measurements from AFM experiments. The SMD simulations were markedly similar to the AFM breakage data, indicating that MD simulations can be used to reasonably probe mechanical properties of amyloid fibrils.
Recommended Citation
Ingwerson, Adam, "Flora and Fauna Lexical Indicators of Prehistoric Movement of Yuman Peoples" (2024). Master's Theses. 5508.
DOI: https://doi.org/10.31979/etd.ykuc-zd4d
https://scholarworks.sjsu.edu/etd_theses/5508
