We have developed a facile mass spectrometric technique called Selective Non-covalent Adduct Protein Probing (SNAPP-MS) to quickly distinguish between the numerous conformations a protein can adopt as well as extracting valuable side-chain availability information. SNAPP-MS experiments are elegantly simple but can potentially reveal significant differences between folded and misfolded proteins (e.g. investigating what surface interactions change to produce amyloidogenetic conformations). Experimental side-chain availibility can also be used in de novo structure determination by restricting the conformational search space.

18-crown-6 ether (18c6), top left, selectively forms weak, non-covalent adducts with the the protonated ε-amino group of lysine residues. Recently published data using several well-studied proteins demonstrates that 18c6 is an effective reporter molecule for lysine availability. We are currently investigating other adduct-forming molecules as well as exploring interesting systems using 18c6.