The primary focus of the proposed research on various properties of DNA including: (i) the dynamic and structural properties of DNA, (ii) the properties of DNA liquid crystals. The first studies focus primarily on the """"""""intrinsic"""""""" properties of DNA, whereas the hydration studies are concerned with understanding how water interacts with DNA. The liquid crystal studies deal with problems of understanding how DNA molecules spontaneously organize into three-dimensional structures in concentrated solutions. An understaning of the physical properties of DNA is crucial to an elucidation of how DNA functions in vivo. A major part of the research is therefore directed to studying sequence effects on DNA properties that are believed to be biologically significant, including the conformation and dynamics of DNA, and the hydration of DNA. 2H NMR will continue to be the major tool used in our studies, but NMR measurements using other nuclei (15N, 6Li, 7Li, 23Na, 31P, 25Mg) will be used to provide additional information. Sequence effects on DNA properties will be examined using samples of deuterated low molecular weight synthetic DNAs incorporated as guests in uniaxially oriented fibers of non-deuterated calf thymus DNA. The affect of DNA length and temperature on NMR relaxation rates will be used to further characterize the nature of the molecular motions. The properties of A-DNA will be compared with B-DNA. Studies on Z-DNA, as a guest in calf thymus DNA fibers, as a powder or as a liquid crystal will also be studied to provide additional information on the properties of this unusual DNA. Hydration plays a crucial role in regulating the physical properties and the in vivo function of DNA and, therefore, an important component of the proposed research will be devoted to an examination of the interaction of water with well characterized samples of uniaxially oriented DNA, frozen solutions of DNA or DNA liquid crystals. A variety of 2H NMR experiments are described to probe the effect of DNA sequence, conformation and nature of counter ions on the water-DNA interaction. NMR studies of cations will provide complementary information. The interaction of organic solvents and their effect on the DNA-water interaction will also be examined using these techniques. DNA liquid crystals are the third topic to be investigated. These systems are of interest in connection with the packaging of DNA in vivo, they provide good systems for testing the theories of liquid crystals of rod like molecules, and they may eventually be useful in other spectroscopic studies of DNA molecules and their complexes.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Biophysics and Biophysical Chemistry A Study Section (BBCA)
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University of California San Diego
Schools of Arts and Sciences
La Jolla
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