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Research in the Carey lab focuses on the development and application of Raman spectroscopy to probe the structure and dynamics of enzyme-substrate intermediates. Many studies involve following reactions in single protein and nucleic acid crystals, an approach termed Raman crystallography. Thus, compounds such as drug candidates can be infused into crystals and, by employing Raman difference spectroscopy, Raman data are obtained for the drug bound in the active site. Analysis of the data yields structural information that provides key insights into factors such as the molecular basis of drug resistance. A parallel approach on crystals of RNA ribozymes has shown that unique information can be obtained on the properties of active site groups and the chemistry of metal binding. Constant efforts are underway to “push the envelope” to extend the size and complexity of the systems under analysis. Recent experiments provide detailed, time-resolved data on the synthesis of a RNA dimer in a RNAPolymerase-DNA crystalline complex with a molecular weight in excess of 120,000 Daltons.
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