Date of Completion
Dr. Zahrasadat Alavi
Dr. Jonas Mureika
Dr. David Berube
This thesis studied the Guanylate Kinase (GK) enzyme, which catalyzes the reaction of ATP into ADP, using nano-rheological techniques. A unique experimental setup was created in order to observe the conformational dynamics of the biological macromolecules. An oscillatory force was applied by attaching enzymes to a gold-coated surface and gold nanoparticles. An additional gold-coated surface was placed on top of the setup in order to create a parallel plate capacitor configuration. An oscillatory voltage was then applied across the capacitor to drive the gold nanoparticles and exert a force on the enzymes. The setup detected the ensemble averaged movement of the enzymes at the Angstrom scale in order to measure the conformational dynamics. The results of the enzyme deformation revealed that they conformationally change according to a viscoelastic regime. At low frequency oscillations, the enzymes acted like a viscous fluid while at high frequencies, the enzymes were elastic like a stiff spring. Due to the disruption of the COVID-19 pandemic, this thesis transitioned to studying the enzyme computationally using molecular dynamics simulations. The results of this thesis are a better understanding of the conformational dynamics of the enzyme which can lead to improved medicinal applications and more targeted molecular dynamics studies in biochemistry and biophysics. Future work includes experimenting with different chemical solutes in solution with the enzymes to measure how the conformational dynamics change and using the molecular dynamics simulations to tailor the experimental approach.
Foss, Calvin, "Exploring the Dynamics of Biological Macromolecules at Angstrom Scale" (2021). Honors Thesis. 375.