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

核酸分子并不是以刚性和统一的结构存在的。具有一定碱基序列的DNA分子具有特殊的结构，可能起到遗传信号的作用。我们通过X射线测定确定了一些有趣的结构。核磁共振测量和分子动力学模拟。1.合成了含腺嘌呤链段的DNA分子d(CGCAAAAAAGCG)：d(CGCTTTTTTGCG)，并测定了其晶体结构。结晶状态下没有观察到弯曲构象。2.在室温下对上述DNA分子进行了500 Mz质子核磁共振测量。分析了核Overhaser效应，计算了质子-质子距离约束下的分子动力学模拟。得到的分子结构有两个严格的弯曲位。这两个弯曲部位都存在于腺嘌呤束区和非腺嘌呤束区之间。腺嘌呤束区未见弯曲。这些结果支持腺嘌呤肌束弯曲机制的废弃模型。3.抗肿瘤药物顺铂(cis-pt)在两个相邻鸟嘌呤碱基的N7位采用。通过对d(CGAACGGCGCG)：d(CGCCTTGCG)的顺铂配合物的500 Mz质子核磁共振测量，药物与DNA双螺旋的结合破坏了DNA的稳定性，但没有破坏碱基配对中氢键的形成。通过模型研究，提出了药物附着部位的扭结构象，并在小凹槽处形成开放形态。4.通过分子力学和动力学模拟计算，寻找出适合I-A碱基配对的DNA分子构象。具有相似构象能的两种可能的构象是可以改变的。这与d(CGCIAATTAGCG)的核磁共振研究结果一致。

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).