THERMODYNAMICS OF DNA CONFORMATION AND INTERACTIONS

DNA 构象和相互作用的热力学

• 批准号: 2181274
• 负责人: LUIS ARNALDO MARKY
• 金额: $ 16.63万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1996-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2181274
• 关键词: THERMODYNAMICS; DNA; CONFORMATION; INTERACTIONS

A complete quantitative description of the energetics of nucleic acid structure, conformational changes and interactions is one prerequisite for a detailed understanding of the biological function of nucleic acids. The role of hydration in determining the physical properties of nucleic acids is widely assumed to be important, but quantitative data are lacking. In this proposal, I plan to continue to carry out a series of systematic measurements of the changes in volume accompanying fundamental physical processes in nucleic acids, including base pairing, ion and ligand binding. I will 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. Effects of nearest-neighbor sequence, bulges, mismatches, as well as conformational variations, including bends, hairpin loops, and branches will be included in this description. complete thermodynamic profiles will be measured on sets of oligonucleotides of appropriate sequence and structure, using a combination of densimetric, calorimetric, spectroscopic and ultrasound velocity measurements. Using a similar thermodynamic approach, we will use the interaction of netropsin, distamycin A and bis-netropsin with short duplexes containing single and multiple binding sites to probe the hydration of the minor groove of B DNA, triplexes and the grooves of parallel DNA. The hydration of the major groove of B-DNA will be monitored using the complementary interaction of DNA oligomer chains with the major groove of homopurine/homopyrimidine polymer duplexes to form triplexes. Alternatively, the hydration of the immediate environment of the major groove can be followed with extrahelical bulges. The relative hydration of triplexes will be determined from complementary adiabatic compressibility measurements on these complexes as a function of temperature and sequence. Comparisons of the volume change between small sets of deoxy and ribo oligomers of similar sequence will be used to try to understand the differences in the thermodynamics of DNA and RNA. A high sensitivity temperature scanning velocimeter will be constructed for the measurement of ultrasound velocity as a function of temperature, which nicely complement the deltaV measurements.

核酸的能量的完整定量描述 结构，构象变化和互动是一种先决条件 为了详细了解核酸的生物学功能。 水合在确定核的物理特性中的作用 广泛认为酸是重要的，但是定量数据是 缺乏。 在此提案中，我计划继续进行一系列 系统测量的量变化伴随着基本的变化 核酸的物理过程，包括碱基配对，离子和 配体结合。 我将将这些值与热量和熵相关联 在同一样品上确定以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，以及用于序列特定的药物结合相互作用。 最近的邻居序列，凸起，不匹配以及 构象变化，包括弯曲，发夹环和分支 将包括在此描述中。 完整的热力学轮廓 将在适当序列的寡核苷酸和 结构，结合密度，量热的结合 光谱和超声速度测量。 使用类似的热力学方法，我们将使用 Netropsin，Distamycin A和Bis-Netropsin，含有短复式 单个和多个结合位点，以探测小调的水合 B DNA的凹槽，三元和平行DNA的凹槽。 这 B-DNA的主要凹槽的水合将使用 DNA低聚物链与主要凹槽的互补相互作用 同孕/同幼酰亚胺聚合物双链体的形成三元。 另外，专业的直接环境的水合 可以用毛细管外凸起跟随凹槽。 相对水合 三胞胎的互补绝热将确定 这些复合物的可压缩性测量是 温度和序列。 小型之间的体积变化的比较 类似序列的一组脱氧和Ribo低聚物将用于尝试 了解DNA和RNA热力学的差异。 将构建高灵敏度温度扫描速度计 为了测量超声速度作为温度的函数， 可以很好地补充Deltav测量值。