Biological and Chemical Physics Commons^™

Aspects Of Stochastic Geometric Mechanics In Molecular Biophysics, David Frost

All Dissertations

In confocal single-molecule FRET experiments, the joint distribution of FRET efficiency and donor lifetime distribution can reveal underlying molecular conformational dynamics via deviation from their theoretical Forster relationship. This shift is referred to as a dynamic shift. In this study, we investigate the influence of the free energy landscape in protein conformational dynamics on the dynamic shift by simulation of the associated continuum reaction coordinate Langevin dynamics, yielding a deeper understanding of the dynamic and structural information in the joint FRET efficiency and donor lifetime distribution. We develop novel Langevin models for the dye linker dynamics, including rotational dynamics, based …

Inhibitors Of Alpha-Synuclein Aggregation, Jemil Ahmed

Electronic Theses and Dissertations

Alpha-Synuclein (αS) – a neuronal, disordered, presynaptic protein – aggregates into amyloid fibrils and accumulates in the substantia nigra pars compacta of Parkinson's Disease (PD) patients. The aggregation and accumulation of αS amyloid fibrils leads to death of dopaminergic neurons; a hallmark of PD. Although it’s not clear why αS aggregates, prior studies have found that intrastriatal injection of fibril alone is sufficient to cause PD pathology in mouse and non-human primates models. These observations implicate αS as a therapeutic target against PD.

Unfortunately, there are three caveats when attempting to target αS. First, αS is a neuronal protein expressed …