Do ionic charges in ESI MS provide useful information on macromolecular structure?

Multiple charging is an intrinsic feature of electrospray ionization (ESI) of macromolecules. While multiple factors influence the appearance of protein ion charge state distributions in ESI mass spectra, physical dimensions of protein molecules in solution are the major determinants of the extent of multiple charging. This article reviews the information that can be obtained by analyzing ionic charge state distributions in ESI MS, as well as potential pitfalls and limitations of this powerful technique. We also discuss future areas of growth with particular emphasis on applications in structural biology, biotechnology (protein-polymer conjugates), and nanomedicine.