X-RAY AND NEUTRON SCATTERING STUDIES OF COLLECTIVE MOTIONS IN PROTEINS

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Proteins undergo structural fluctuations in aqueous solution that appear to be critical for many functions. Although NMR and x-ray crystallographic studies have taught us a great deal about small, fast, local motions of the side chain atoms, the larger scale breathing motions remain poorly characterized. This proposal involves a set of coordinated x-ray and neutron scattering experiments designed to characterize breathing motions of proteins in solution in terms if both scale and dynamics; determine the effect of solvent constituents and temperature on those motions; and demonstrate how molecular crowding impacts those motions. We have discovered a concentration- dependence that reflects relatively large scale structural fluctuations that increase in magnitude with decreasing concentration. Coordinated WAXS and inelastic neutron scattering experiments will be carried out on structurally well characterized proteins for which our group has obtained a large body of preliminary data. WAXS data will be collected at the APS over a wide concentration range at multiple temperatures, with data modeled in terms of the structural fluctuations that are occurring in the protein. Neutron spin-echo data will be collected at NIST/ILL for the same proteins. Data from WAXS/SANS experiments will be correlated, interpreted and modeled in terms of the dynamic motion of secondary structures within the proteins. Additional x-ray and neutron experiments will be designed to support and further enhance the value of the neutron data collected. The results of these studies should provide detailed information on the large-scale, correlated motions of proteins in solution.