THERMODYNAMICS OF DNA CONFORMATION & INTERACTIONS

DNA 构象的热力学

• 批准号: 3300752
• 负责人: LUIS ARNALDO MARKY
• 金额: $ 10.78万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3300752
• 关键词: RNA; X ray crystallography; calorimetry; chemical binding; chemical hydration; chemical structure function; conformation; densitometry; netropsin; nucleic acid chemical synthesis; nucleic acid structure; nucleic acids; nucleobase; oligonucleotides; polynucleotides; spectrometry; synthetic nucleotide; thermodynamics

A quantitative description of the energetics of nucleic acid structure, conformations and interactions is prerequisite for a detailed understanding of the biological function of DNA and RNA. In this proposal, I plan to carry out systematic measurements of the changes in volume accompanying fundamental physical processes in nucleic acids, including base pairing, ion and ligand binding, and correlate these values with heats and entropies determined on the same samples to provide a complete set of thermodynamic parameters for base-pairing of chains containing any sequence of complementary bases and for sequence specific drug binding interactions. The role of hydration in these processes is assumed to be important, but no such systematic values have been reported. Effects of mismatches, nicks, as well as conformational variations, including bends, hairpin loops, bulges and branches will be included. Parameters will be determined from complete thermodynamic profiles measured on sets of oligonucleotides of appropriate sequence and structure, using a combination of densimetric, calorimetric and spectroscopic techniques. Comparisons of the centered values between deoxy and ribo oligomers of similar sequence will be used to try to understand the differences in thermodynamics of DNA and RNA. Combined densimetry, calorimetry and spectroscopy will also be used to define the thermodynamics of netropsin, distamycin A and actinomycin D binding to oligonucleotides containing single binding sites. A high sensitivity magnetic suspension densimeter will be constructed following the design of Kupke, and used to make these measurements.

核酸能量的定量描述 结构，构象和互动是一个先决条件 详细了解DNA和RNA的生物学功能。 在此提案中，我计划进行系统的测量 伴随基本物理过程的体积变化 在核酸中，包括碱基配对，离子和配体结合， 并将这些值与确定的热量和熵相关联 相同的样品可提供一组完整的热力学 用于基本配对的参数，该链包含任何序列 互补碱和用于序列特定药物结合 互动。 假定水合在这些过程中的作用 重要的是，但是尚未报告这种系统值。 不匹配，划痕和构象的影响 变化，包括弯曲，发夹环，凸起和分支 将包括在内。 参数将从完整确定 测量的热力学特征在寡核苷酸的集合 合适的序列和结构，结合 密度，量热和光谱技术。 比较脱氧和Ribo低聚物之间的中心值 类似的顺序将用于尝试了解 DNA和RNA热力学的差异。 密集型法， 量热法和光谱法也将用于定义 Netropsin，Distamycin A和放线霉素D结合的热力学 到包含单个结合位点的寡核苷酸。 高 灵敏度磁悬浮量密度计的构造 遵循库普克的设计，并用于进行这些测量。