The McLafferty group has developed “top-down proteomics” utilizing electrospray mass spectrometry for characterization of a protein’s sequence and modifications by dissociation of its gaseous multiply-protonated ions. Current research shows that dissociation varies with conformation, which differs surprisingly from native solution conformations, as shown by H/D exchange, electron capture dissociation, and infrared photodissociation spectroscopy.

Research Molecular mass spectrometry involves theory, mechanisms, instrumentation, computerization, and applications to polymers and biomolecules Our instrumentation combining Fourier-transform mass spectrometry with electrospray ionization gives accurate (±1 Da) molecular weight values for proteins at the 10-18 mol level with MS/MS identification of proteins at the 10-17 mol level Our "top down" tandem MS technique for the characterization of proteins provides specific localization of posttranslational modifications, such as glycosylation, oxidation, and proteolysis Our new technique of electron capture dissociation provides high specificity for such characterizations, cleaving 251 of the possible 258 interresidue bonds in a 29 kDa protein and providing cleavages in a 24 kDa casein that would identify phosphorylations at all 26 of its potential sites