Keywords: Bimolecular mass spectrometry; Analytical instrumentation; Molecular structural elucidation of macromolecular assemblies; Pixelated detectors

"Technological Developments in Mass Spectrometry Towards Molecular Structural Elucidation of Macromolecular Assemblies"

Retrieving higher-order structural features of macromolecular assemblies (MMAs), such as protein complexes and viruses, is of great interest. These characteristics are crucial for understanding the functions and interactions of MMAs with other molecular species or receptors. While various techniques such as cryogenic-electron microscopy, nuclear magnetic resonance, and x-ray crystallography are capable of providing high-resolution structures of MMAs, they come with some limitations. This thesis primarily focuses on the technological developments in mass spectrometry (MS) in retrieving molecular features of MMAs at different levels of their organization. For that, aspects of soft-ionizing techniques (nano-electrospray ionization and matrix-assisted laser desorption/ionization), axial/orthogonal reflectron time-of-flight and high-resolution Orbitrap MS, top-down proteomics (ultraviolet photodissociation and higher-energy collisional dissociation), and mass-to-charge ratio/time-resolved imaging using pixelated Timepix and Timepix3 application-specific integrated circuit based detection assemblies were brought together.

Click here for the full dissertation.

Click here for the live stream.