Zhe Zhang

Mass spectrometry is playing an increasingly important role in the study of protein structure and dynamics. Two novel and powerful application of it were developed, and will be presented in my talk as described below.

When electrosprayed from native-like solutions into the gas phase, protein ions are thought to maintain some of their structural features, especially electrostatic interactions. In mass spectrometry (MS), collision induced dissociation (CID) can disrupt covalent and non-covalent bonds, however, electron transfer dissociation (ETD) can break covalent bonds without disrupting non-covalent interactions. By applying ETD and CID in sequence as a strategy, we have demonstrated its capability to study the locations of protein electrostatic interactions. The results provide evidence that electrostatic interactions that exist in solution can be maintained in the gas phase. A simulation of possible protein structures was also performed to confirm this conclusion.

Hydrogen/deuterium exchange (HDX) is mostly used to explore protein backbone structure and we extended this technology to understand protein dissociation and association kinetics. HDX is performed simultaneously with the transition between two different oligomer states (e.g. dimer/monomer). Following mathematical processing, we are able to obtain rate information for oligomer transition. The methodology has proven to be able to measure oligomer kinetics that range from 1 x 10^-4 s^-1 to ~1 s^-1.