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Current Interests Virus structure and assembly, protein-nucleic acid recognition, DNA and RNA structures, protein conformation; development of laser Raman spectroscopy as a probe of structure, interaction and dynamics in biomolecular assemblies.
Summary The principal objective of our research is to understand the molecular basis of protein-nucleic acid recognition. Current studies focus on viruses, telomeric DNA complexes and gene regulatory systems. The specific aims of this work are to: (i) determine the interactions of protein and nucleic acid subgroups leading to the proper assembly and stability of viruses and chromosomal assemblies; (ii) establish the detailed structures and conformations of nucleic acid and protein molecules in these assemblies; and (iii) identify chemical and biological factors that control stability and polymorphism in macromolecular complexes. These aims are pursued by combining biochemical and molecular biological probes with state-of-the-art spectroscopic methods, including laser Raman, ultraviolet resonance Raman (UVRR) and Fourier-transform infrared (FTIR) spectroscopy. The structural interpretation of results on viruses and other nucleoprotein assemblies is aided by parallel studies of model nucleic acids, proteins and their complexes. Studies are in progress on filamentous (Ff, Pfl, Pf3, H75) and isometric viruses (P22, PRD1, HK97, f6, HIV1), gene regulatory complexes, telomeric DNA/protein complexes and condensed states of DNA.
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We are also interested in biomolecular dynamics that occur on time scales
greater than the periods of molecular vibrations. Work in progress includes
the investigation of protein folding in the tailspike protein of bacteriophage
P22, the determination of nucleic acid and protein dynamics in virion assemblies
and the kinetics of structural transformations that control virion architecture
during morphogenesis.