Integrated Platform for Mass Spectrometric Studies of Protein Structure

Summary Technology for studying the higher order structure HOS of biomolecules encompasses some of the most important tools in all of science and is a highlighted NIGMS research topic Mass spectrometric methods for studying HOS include oxidative footprinting and other methods to covalently label amino acid side chain functional groups and also hydrogen deuterium exchange HDX on protein backbone amides These methods require only small amounts of not necessarily pure material and can study conformation and dynamics of proteins in solution with or without ligands Mass spectrometric methods are especially well suited to biopharma comparability and epitope mapping studies Currently there is no software that can analyze mass spectrometric data from both chemical labeling and HDX experiments even though the two methods both probe solvent accessibility and if combined would give finer resolution and greater confidence Protein Metrics has already built beta test software for covalent labeling including Fast Photochemical Oxidation of Proteins FPOP The proposed project will focus on data analysis software for HDX experiments The outcome will be vendor neutral software with advanced analytical and reporting capabilities that can handle both HDX and covalent labeling experiments Narrative The higher order structure HOS of biomolecules determines function binding partners immune response and safety and efficacy of therapeutics Mass spectrometric methods for studying HOS include hydrogen deuterium exchange and covalent labeling experiments such as oxidative footprinting The proposed project will result in unique software to analyze all types of mass spectrometric data for HOS studies and will find use in both academic research and the biopharmaceutical industry