Direct visualization of functionally relevant protein dynamics is critical for the mechanistic understanding of many biochemical reactions and biological processes. However, it remains challenging to conduct dynamic crystallographic experiments at room temperature and to extract dynamic information from crystallography data. On the other hand, the crystal structures of the same protein family have been repeatedly determined and deposited to the Protein Data Bank (PDB). While each structure represents a snapshot of the protein structure, an ensemble of protein structures from the same system or family could convey dynamic information. In this dissertation, I will present three projects: (1) Uncovering the common characteristics of cholesterol binding sites in membrane proteins by examining the spatial distributions of cholesterol with respect to the protein framework in 57 PDB entries of the G-protein coupled receptor (GPCR) proteins. (2) Joint analysis of 527 GPCRs from Class A, B1, C and F using singular value decomposition (SVD) with a goal to identify the structural motions associated with GPCR activation. (3) The development of in situ serial crystallography platform to which I have made contributions as part of a larger effort to enable routine and robust dynamic crystallography experiments at room temperature.
History
Advisor
Yang, Xiaojing
Chair
Yang, Xiaojing
Department
Chemistry
Degree Grantor
University of Illinois at Chicago
Degree Level
Doctoral
Degree name
PhD, Doctor of Philosophy
Committee Member
Miller, Lawrence W.
Snee, Preston T.
Hu, Ying
Ansari, Anjum