Date of Award
Doctor of Philosophy (PhD)
Physics and Astronomy
Proteins, RNA, and DNA serve as the primary sub-cellular machinery that give rise to the necessary functions of life. The long-standing paradigm has been that the structures of biomolecules, or the arrangement of the subunits that make up a biomolecule, determine biological function. However, biomolecules are not static objects. Instead, they often undergo structural rearrangements that are crucial to enabling and regulating their functions. In my thesis I present several studies of the interplay between the structures, dynamics, and functions of biomolecules that combine experimental fluorescence spectroscopy and computational methods to probe these systems at the single-molecule level. In particular, PSD-95, an abundant protein found in human neuronal synapses, exhibits complex structural rearrangements amongst its five structural subunits. Our investigations into the organization of these subunits have unveiled a complex dynamic scheme in which structural rearrangements allow PSD-95 to self-regulate interactions of PSD-95 with itself and other proteins. Such interactions amongst the biomolecular machinery at the single-molecule scale are what underlie macroscopic biological processes like neuroplasticity and cell growth.
Hamilton, George L. III, "Supertertiary Structural Dynamics Modulate Function in Postsynaptic Density Protein 95" (2022). All Dissertations. 2998.
Author ORCID Identifier