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Mass Spectrometry

Electrospray ionization/ion mobility (ESI/IM) mass spectrometry (MS) is a gentle method to derive structural information from measurements of protein ions in the gas phase. It does not require crystallization and it is already sensitive to concentrations well below those required for NMR. However, there is no way to monitor biomolecules at atomic detail by experimental techniques in the gas phase. In collaboration with Dr. S. Raugei at the Pacific Northwest National Laboratory (USA) and Prof. R. Grandori of the University of Milano-Bicocca (Italy), we have first investigated the gas-phase structure of single proteins of variable size and different folds (Marchese et al., PLoS Comput. Biol. 2010. 6, e1000775l; Marchese et al., J. Am. Soc. Mass. Spectrom. 2012. 23(11): 1903-1910). The conformer and protomer space of protein ions has been explored exhaustively by a hybrid Monte-Carlo/molecular dynamics (MC/MD) protocol with a gas-phase basicity correction for the traditional force field. Very recently, we have successfully extended our computational protocol to a protein complex, the human insulin dimer. Our predictions have reproduced the experimental main charge and collision cross section. They have further shown that, in the sub-ms time scale, the final gas-phase structure differs in a subtle manner from the solution structure as it maximizes intra- and intermolecular hydrogen bond interactions.

Mass SpectrometryFigure 1 - Left panel: A schematic model of ESI-MS. The structure of human insulin dimer (hIns2) in solvent was indicated by cartoon representation. Right panel: Models of hIns2 obtained from MD simulations in vacuo are presented in the upper panel. The time evolution of the angle between the center of mass of monomer I – β-sheet region – monomer II is presented in the lower panel.