New Algorithms and Software for Mass Spectrometric Analysis of Intact Proteins and Complexes

Intact proteins and multi-protein complexes represent two of the most important levels of organization in biology, yet these levels are also some of the most difficult to study. Native mass spectrometry provides a means to observe proteins in complex with ligands, other proteins, and nucleic acids. The proposed project will build new algorithms and software for intact and native mass spectrometry. Specifically, the project will further develop Protein Metrics Intact Mass charge-deconvolution software, incorporating multiple information channels (isotope spacing, co-elution, and charge states) into the core algorithm, so that the algorithm can handle complex, low signal-to-noise mass spectra over a wide range of masses and abundances. The project will also build automation software for analyzing data as it is produced by mass spectrometry instruments, naming and organizing files, and producing reports showing results at several levels of detail. The project will enable a number of interesting applications, including small-molecule screening, large-molecule drug comparability, pharmacokinetics, and protein / protein and protein / nucleic acid binding.