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. This proposal covers two projects involving studies of protein-ligand interactions. The first is a continuing search for well-ordered crystals of rhodopsin and its complexes with other signaling proteins. How G protein-coupled receptors respond to their environment and interact with G proteins to create intracellular signals is not understood at the molecular structure level. We are attempting to crystallize complexes relevant to the signaling process and want to use synchrotron radiation to determine their structures. Our current crystals are small and poorly-ordered. How well they diffract would be difficult to determine without access to synchrotron sources. Our second project involves obtaining high or ultra-high resolution diffraction data for streptavidin mutants and their biotin complexes. We want to compare molecular dynamics simulations and anisotropic atomic displacement parameters to better understand the dynamics of protein/small molecule (drug?) interactions. We currently have several high-resolution data sets for the comparison, but we anticipate expanding our studies to include additional mutants.
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