The Utility Of Hydrogen Deuterium Exchange Mass Spectrometry For Characterization Of Proteins And Their Interactions.

Mass spectrometry (MS) offers immense versatility to the structural biology field. Particularly, Hydrogen Deuterium Exchange MS (HDX-MS) can overcome obstacles encountered by more traditional, higher resolution structural characterization methods. What happens when your protein system is just too big, dynamic, dilute, or poorly soluble? Recent advancements in structural prediction and HDX-MS automation have enabled some of the fastest data turnaround to date. This work follows many different scenarios where HDX-MS and MS have been employed, including protein-peptide interactions of the Bcl-2 family, affinity ranking and prediction of a focused small molecule library targeting WDR5, USP3 binding characterization of a small molecule screen hit, the detection of proteolysis targeting chimera (PROTAC)-induced ternary complex formation, and epitope mapping of antibodies targeting the SARS-CoV-2 Spike protein, all made possible by the collaboration of the Dickinson Lab (University of Chicago), Icosagen (Estonia), the Ingerman-James Lab (University of North Carolina at Chapel Hill), and the Structural Genomics Consortium.