TRANSITION METAL DNA COMPLEXES--INSULATORS OR WIRES

过渡金属 DNA 络合物——绝缘体或电线

• 批准号: 6180972
• 负责人: DAVID BERATAN
• 金额: $ 17.81万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6180972
• 关键词: DNA; bioenergetics; computer simulation; electron transport; heavy metals; mathematical model; metal complex; nucleic acid sequence; nucleic acid structure; oxidation reduction reaction; oxidizing agents; reducing agents

Nucleic acid biosynthesis, regulation of genetic information, and radiation damage/repair proceed via electron transfer (ET) reactions, often involving transition metal complexes [1-6]. ET in these systems occurs over large distances, well beyond van der Waals contact. The fundamental ET mechanism is under intense current investigation, but remains the subject of substantial debate [7-10]. Experiments reported in the last five years appear to be in dramatic conflict [11-13]; the most basic question of how far and how fast electrons can travel between metal complexes attached to DNA remains open [14]. In instances of this kind, theory can play a particularly important role in unraveling apparent conflicts by charting the accessible mechanist regimes. More importantly, theory can help design new experiments that will provide the critical tests of proposed electron transfer mechanisms. The goal of this study is to employ modern methods of electronic structure theory and molecular dynamics simulation to place constraints upon how far and how fast electron transfer may proceed in DNA. The critical aims of this project are: (1) to determine how sensitive DNA electron transfer rates are to the energetics of the donor (D) and acceptor (A) redox active transition-metal groups and DNA sequence when the energy levels of donor and acceptor are far from the energies of the base pair levels, (2) to determine how sensitive DNA electron transfer rates are to the energetics of the donor and acceptor redox active transition-metal groups and DNA sequence when the energy levels of donor and acceptor are close to the energies of the base pair levels, (3) to determine how the rich dynamical fluctuations in three-dimensional DNA structure (including hydration) modulate the donor-acceptor interaction. This project will employ both semi-empirical [15] and linear scaling ab initio electronic structure methods [16,17] to compute the donor- acceptor electronic interaction. Molecular geometries used in these calculations will be sampled from molecular mechanics and classical molecular dynamics simulations. Finally, electron transfer reorganization energies will be calculated [18-20]. Taken together, these three investigations will be used to build a comprehensive theory of DNA electron tunneling processes, and should reveal the dependence upon donor/acceptor binding motif and energetics, , DNA sequence, and the dynamical fluctuations of the DNA structure.

核酸生物合成、遗传信息调节和辐射损伤/修复通过电子转移 (ET) 反应进行，通常涉及过渡金属配合物 [1-6]。这些系统中的 ET 发生的距离很远，远远超出了范德华接触范围。 ET 的基本机制目前正在紧张的研究中，但仍然是大量争论的主题 [7-10]。 过去五年报告的实验似乎存在巨大的冲突[11-13]；电子在附着于 DNA 的金属复合物之间移动的距离和速度这一最基本的问题仍然悬而未决 [14]。 在这种情况下，理论可以通过绘制可理解的机械论体系来解决明显的冲突，从而发挥特别重要的作用。 更重要的是，理论可以帮助设计新的实验，为所提出的电子转移机制提供关键测试。本研究的目标是采用电子结构理论和分子动力学模拟的现代方法来限制 DNA 中电子转移的距离和速度。 该项目的关键目标是：（1）确定当供体和受体的能级远离碱基对能级的能量时，DNA电子转移速率对供体（D）和受体（A）氧化还原活性过渡金属基团和DNA序列的能量有多敏感，（2）确定DNA电子转移速率对供体和受体氧化还原活性过渡金属基团和DNA的能量有多敏感 当供体和受体的能量水平接近碱基对水平的能量时进行序列，（3）确定三维DNA结构（包括水合）中丰富的动态波动如何调节供体-受体相互作用。 该项目将采用半经验[15]和线性缩放从头开始电子结构方法[16,17]来计算供体-受体电子相互作用。 这些计算中使用的分子几何形状将从分子力学和经典分子动力学模拟中采样。 最后，将计算电子转移重组能[18-20]。总而言之，这三项研究将用于建立 DNA 电子隧道过程的综合理论，并应揭示对供体/受体结合基序和能量、DNA 序列以及 DNA 结构的动态波动的依赖性。