Abstract/Summary

Understanding protein structure is vital for evaluating protein interactions with drugs, proteins and other ligands. Native mass spectrometry (MS) is proving to be invaluable for this purpose, enabling analysis of ’native-like’ samples that mimic physiological conditions. Native MS is usually performed by electrospray ionization (ESI) with its soft ionization processes and the generation of multiply charged ions proving favourable for conformation retention and high mass analysis, respectively. There is scope to expand the currently available toolset, specifically to other soft ionization techniques such as soft laser desorption, for applications in areas like high-throughput screening and MS imaging. In this letter, observations made from native MS experiments using an ultraviolet (UV) laser-based ion source operating at atmospheric pressure are described. The ion source is capable of producing predominately multiply charged ions similar to ESI. Proteins and protein complexes were analyzed from a native-like sample droplet to investigate the technique. Ion mobility-mass spectrometry (IM-MS) measurements showed that folded protein conformations were detected for ions with low charge states. This observation indicates the source is suitable for native MS analysis and should be further developed for higher mass analysis in the future.