Structure and dynamics of DNA hairpins

将对RNA和DNA进行固态和溶液核磁共振综合研究，重点关注化学位移作为主要的光谱观察。15N和13C屏蔽张量将通过实验确定DNA和RNA的主要种类和构象，并将通过量子化学计算进行补充和扩展，以全面了解核酸中化学位移与构象之间的关系：通过判别分析方法从化学位移和屏蔽张量数据中确定构象的程度和准确性，这些统计信息将作为核磁共振结构确定的改进方案中的加权因素。收集了一小组DNA发夹和微型发夹在固体、各向同性溶液和取向溶液状态下的化学位移谱，定量了动力学和晶体与溶液结构差异对核磁共振谱的影响。希望最终结果将是：(i)改进确定DNA和RNA结构和动力学的方法；（ii）充分了解与许多正常和疾病状态有关的DNA发夹的结构和动力学。

An integrated solid-state and solution NMR study of RNA and DNA will be conducted, focusing on the chemical shift as a primary spectroscopic observable. 15N and 13C shielding tensors will be experimentally determined for the major DNA and RNA species and conformations, and these will be supplemented and extended by quantum chemical calculations, to give a comprehensive picture of the relationship between chemical shift and conformation in nucleic acids: The extent to and accuracy with which conformation can be determined from chemical shift and shielding tensors data by the methods of discriminant analysis, and this statistical information will be incorporated as a weighting factor in refinement protocols for NMR structure determination. Chemical shift spectra will be collected for a small set of DNA hairpins and minihairpins in the solid, isotropic solution and oriented solution state, and the effect of dynamics and of difference between the crystalline and solution structure on the NMR spectrum quantified. The end result will it is hoped be (i) improved methods for determining DNA and RNA structure and dynamics and (ii) a full understanding of the structure and dynamics or DNA hairpins, which have been implicated in a number of normal and disease states.