TRANSITION METAL DNA COMPLEXES--INSULATORS OR WIRES

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，通常涉及过渡金属络合物[1-6]。在这些系统中，ET发生在大的距离上，远远超过货车德瓦耳斯接触。 ET的基本机制目前正在进行深入的研究，但仍然是实质性辩论的主题[7-10]。 在过去五年中报道的实验似乎是在戏剧性的冲突[11-13];最基本的问题是多远和多快的电子可以在连接到DNA的金属复合物之间旅行仍然开放[14]。 在这种情况下，理论可以通过绘制可访问的机械主义制度，在解决明显的冲突方面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，为提出的电子转移机制提供关键的测试。本研究的目的是采用现代电子结构理论和分子动力学模拟的方法来限制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序列的能量学的敏感程度，（2）确定DNA电子转移速率对供体和受体氧化还原活性跃迁的能量学有多敏感-当供体和受体的能级接近碱基对能级的能量时，（3）确定DNA三维结构中丰富的动力学涨落（包括水合作用）如何调节供体-受体相互作用。 该项目将采用半经验[15]和线性标度从头计算电子结构方法[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取样。 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电子隧穿过程的全面理论，并且应该揭示对供体/受体结合基序和能量、DNA序列以及DNA结构动态波动的依赖性。

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.