The goal of the project is to provide significant new technologies for biomedical research. These technologies build on the success of well-established structural biology techniques, and significantly advance the amount of information obtainable on a diverse range of biological systems. Specifically, the technologies developed will be used to map solvent accessible regions in macromolecules on a timescale of microseconds, yielding information on conformation, protein-protein dynamics, and bound water location and dynamics. The technologies will be appropriate for studying large protein complexes, proteins in membranes, and macromolecular structures in cell fractions, and will be developed for both static structure and for delineating structural changes as a function of time on the microsecond timescale. Proof of principle for these technologies is presented, along with preliminary data, and the proposal outlines the significant technical challenges involved and how they will be overcome. Automation and throughput are part of the new capabilities and will enable access to the new technologies to a wide user base in the biomedical research community.
The technological advances developed in this proposal will enable novel research capabilities relevant to the most pressing biomedical research problems today. New instrumentation and methodologies presented here will enable researchers to obtain deep insight into structural and dynamics of a range of biological macromolecules, from membrane proteins to large macromolecular machines.