High Throughput Screening by Native Mass Spectrometry - Identifying binders, with the desired functionality, to membrane protein and intricate targets.
Abstract: Native mass spectrometry (MS) has emerged as a biophysical tool to characterize proteins and their interacting partners in a near native ecosystem. To date there have been a plethora of studies using native MS to derive structural information of protein complexes, their oligomeric state, characterize the functions of posttranslational modifications have protein-protein complex formation, identification of structurally and functionally import lipids and metabolites as well as reporting therapeutics bound to target proteins. However, most of native MS analysis are performed manually limiting the number of measurements that can be acquired. Our OdyssIONTM drug discovery platform overcomes this challenge and enables high throughput label free screening by native MS of over 200k compounds. Our method preserves the link between binding and function, driving fast hit ID and lead optimization. It also captures a broad range of affinities and has the ability to unlock novel biology by identifying endogenously unknown regulatory molecules. Our fundings will be discussed in the context of identifying binders that modulate the function of G-protein coupled receptors, solute carriers and targets involved in inflammatory regulated cell death.