Structure and dynamics of DNA hairpins

我们将对RNA和DNA进行固体核磁共振和溶液核磁共振研究，重点放在作为主要光谱观察物的化学位移上。15N和13C屏蔽张量将通过实验确定主要DNA和RNA物种和构象的15N和13C屏蔽张量，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和构象之间的关系：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精度，这一统计信息将作为加权因子纳入核磁共振结构确定的精化协议中。收集了一小部分DNA发夹和小发夹在固体、各向同性溶液和定向溶液状态下的化学位移谱，并量化了动力学和晶体与溶液结构差异对核磁共振谱的影响。最终的结果有望是(I)改进确定DNA和RNA结构和动力学的方法，以及(Ii)充分了解DNA发夹的结构和动力学，这些发夹与许多正常和疾病状态有关。

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.