Structual Studies for Nucleic Acids Conformation as Genetic Signal and Regulational Signal

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Nucleic acid molecules don't exist as a rigid and uniform structure. DNA molecules with a certain base sequence has a special structure which may act genetic signal. We determined some interesting structures by X-ray determination. NMR measurement and molecular dynamic simulation. 1. DNA molecule with adenine tract which causes a bending structure, d(CGCAAAAAAGCG):d(CGCTTTTTTGCG) was crystallized and its crystal structure was determined. No bending conformation was observed in crystalline state. 2. 500Mz proton NMR measurement of the above DNA molecule was carried at room temperature. Nuclear Overhauser effects were analysed and the molecular dynamic simulations with proton-proton distance restraint were calculations. The obtained molecular structure has two strictly bending sites. Both bending sites exist between adenine tract region and non-adenine tract region. No bending was observed in adenine tract region. These results support the junkction model for bending mechanism of adenine tract. 3. An antitumor agent, cis platinum (cis-Pt) adopts at N7 positions of two adjacenting guanine bases. By 500Mz proton NMR measurement of cis-Pt complex with d(CGAACGGCGCG):d(CGCGCCTTGCG), drug attachment to DNA double helices destabilizes but causes no breakdown of hydrogen bond formation in base pairing. by the model study, the kink conformation at drug attached site with open form at minor groove is proposed. 4. The suitable conformations of DNA molecule with I-A base pairing, were seeked by molecular mechanics and dynamic simulation calculations. Two possible conformations which have a similar conformational energy, can be changable. These are consist with NMR studies of d(CGCIAATTAGCG).