DEPT OF PHYSICS
PHD DISSERTATION DEFENSE
Ph.D. Candidate: Shenglan Qiao
Research Advisor: Sebastian Doniach
Date: Tuesday, Dec 4th, 2018
Location: Clark Center S363
Title: Developing angular intensity correlations of X-ray photons as a tool for studying structures of proteins in non-crystalline solutions
In his 1977 paper, Kam proposed the idea of correlating X-ray photons scattered by an ensemble of randomly oriented particles suspended in solution. He found that if the exposure time is much shorter than the diffusion timescale of Brownian motion, correlations between photons scattered into different angles encode three-dimensional (3D) structural information of the particles not accessible via conventional small or wide-angle X-ray scattering. The advent of the X-ray free electron laser (XFEL) renders Kam's idea feasible for non-crystalline solutions of proteins. With femtosecond pulses and extremely high fluences, the XFEL is not only capable of probing ensembles of molecules essentially frozen in time but also delivering a large number of photons per pulse, a capability critical for enhancing angular intensity correlation signals. Meanwhile, probing proteins in solution removes the need for crystallization, allows measurements of mixtures of conformational states under physiological conditions, and broadens opportunities for time-resolved experiments.
I will present the progress we have made in developing correlated X-ray scattering as a technique for studying molecular structures. My talk will highlight technical tools developed for extracting angular intensity correlations from scattering data collected with samples containing the G-protein Gi alpha subunit during two separate beam times conducted at the Linac Coherent Light Source. The G-protein Gi alpha subunit was chosen as a model system because of its important role in the G-protein coupled receptor signaling pathway. The measured correlations have enabled the representation of the proteins as ensembles of molecular models and their respective occupancies. From these ensembles of models and occupancies, we can then infer 3D structural details of functional importance not accessible via conventional small or wide-angle X-ray scattering.
Reference: Kam, Zvi. “Determination of Macromolecular Spatial Correlation of Scattering.” Macromolecules. Vol. 10, No. 5, September-October 1977