Structure and dynamics of DNA hairpins

DNA发夹的结构和动力学

• 批准号: 6622934
• 负责人: GERARD STANISLAUS HARBISON
• 金额: $ 21.3万
• 依托单位: UNIVERSITY OF NEBRASKA LINCOLN
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622934
• 关键词: DNA; RNA; carbon; computer simulation; conformation; crystallization; molecular dynamics; nitrogen; nuclear magnetic resonance spectroscopy; nucleic acid sequence; nucleic acid structure; quantum chemistry; stable isotope; statistics /biometry; stereochemistry; structural biology

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.

将对RNA和DNA进行综合的固态和溶液NMR研究，重点是作为主要光谱观测的化学位移。15 N和13 C屏蔽张量将通过实验确定主要的DNA和RNA种类和构象，这些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确定构象的程度和准确性，并且该统计信息将作为加权因子纳入NMR结构确定的细化方案中。化学位移光谱将收集一小组的DNA发夹和minihairpins在固体，各向同性的溶液和定向的溶液状态，和动力学和结晶和溶液结构之间的差异的NMR光谱量化的效果。最终的结果是希望（i）改进确定DNA和RNA结构和动力学的方法，（ii）充分理解DNA发夹的结构和动力学，这些结构和动力学与许多正常和疾病状态有关。