Structural Mass Spectometry for protein modeling

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Determining the composition, assembly and dynamics of multi-protein complexes is essential for studying the function of many cellular processes we understand only at a crude level. There is a strong need for new technologies in this area, as these complexes represent a new frontier in drug discovery research. This proposal presents a strategy to develop and explore concepts in Structural Mass Spectrometry (SMS) as a way to model such complexes. SMS is an emerging field that combines "dynamic protein topology" measurements with computational methods, in order to obtain high resolution images. New advancements are needed to obtain these images at sufficient resolution to support detailed investigations into protein function. Unfortunately, mass spectrometry systems and methods have been developed for other applications, and don't readily apply to SMS. Through this research, we will develop new instruments, software and methods to harness the potential of SMS for protein imaging. Our goal is to develop techniques for "coding" protein structure and dynamics into quantities that the mass spectrometer can measure, and then translating these measurements by computer into accurate structural models. Successful completion of this program of studies will provide a powerful new tool for the life sciences, which can be used in basic research and by the pharmaceutical community, with the capacity to accelerate rates of drug discovery.