In recent years mass spectrometry has established itself as a powerful method with which to determine the stoichiometry and conformations of proteins and their complexes.(1-3) Pioneering work in the groups of Robinson, Heck, and Loo, among others, has now established that with careful use of electrospray ionization and gentle transfer into the gas phase, bioactive complexes of significant size can be transported intact into the controlled environment of a mass spectrometer for subsequent analysis.(4) Mass spectra of very large protein complexes,(5) whole ribosomes,(6) and intact viruses(7) have been recorded, as well as several studies on the dynamics of large complex assembly or disassembly.(8-10)

There is, of course, controversy about whether a solution phase structure is retained in its entirety in the solvent-free environment of a mass spectrometer,(4,11) but for large macromolecular systems such as those referred to above, bound by many noncovalent interactions, there is evidence to suggest that macroscopic features of solution and even in vivo structures are retained. The growth and success of studies of macromolecular complexes by mass spectrometry increasingly places biological mass spectrometry as the first step in the structural analysis of unknown or as yet unquantified protein:protein architectures; in short, it now has a role as a predictive tool.