Department for Theoretical Chemical Biology, Institute for Physical Chemistry, Karlsruhe Institute for Technology , Kaiserstr. 12, 76131 Karlsruhe, Germany.
J Phys Chem B. 2013 Sep 19;117(37):10769-78. doi: 10.1021/jp406319b. Epub 2013 Sep 4.
We study fast hole transfer events in E. coli DNA photolyase, a key step in the photoactivation process, using a multiscale computational method that combines nonadiabatic propagation schemes and linear-scaling quantum chemical methods with molecular mechanics force fields. This scheme allows us to follow the time-dependent evolution of the electron hole in an unbiased fashion; that is, no assumptions about hole wave function localization, time scale separation, or adiabaticity of the process have to be made beforehand. DNA photolyase facilitates an efficient long-range charge transport between its flavin adenine dinucleotide (FAD) cofactor and the protein surface via a chain of evolutionary conserved Trp residues on the sub-nanosecond time scale despite the existence of multiple potential trap states. By including a large number of aromatic residues along the charge transfer pathway into the quantum description, we are able to identify the main pathway among alternative possible routes. The simulations show that charge transfer, which is extremely fast in this protein, occurs on the same time scale as the protein response to the electrostatic changes; that is, time-scale separation as often presupposed in charge transfer studies seems to be inappropriate for this system. Therefore, coupled equations of motion, which propagate electrons and nuclei simultaneously, appear to be necessary. The applied computational model is shown to capture the essentials of the reaction kinetics and thermodynamics while allowing direct simulations of charge transfer events on their natural time scale.
我们使用一种多尺度计算方法研究了大肠杆菌光解酶中的快速空穴转移事件，这是光激活过程中的关键步骤。该方法结合了非绝热传播方案和线性标度量子化学方法与分子力学力场。该方案允许我们以无偏的方式跟踪电子空穴的时变演化；也就是说，在此之前，无需对空穴波函数定位、时间尺度分离或过程的绝热性做出任何假设。尽管存在多个潜在的捕获态，但 DNA 光解酶仍能通过一系列进化保守的色氨酸残基在黄素腺嘌呤二核苷酸（FAD）辅因子和蛋白质表面之间实现有效的长程电荷转移，其时间尺度在纳秒以下。通过在量子描述中包含沿电荷转移途径的大量芳香族残基，我们能够在替代可能途径中确定主要途径。模拟表明，在这种蛋白质中，电荷转移速度极快，与蛋白质对静电变化的响应速度相同；也就是说，电荷转移研究中经常假设的时间尺度分离似乎不适合该系统。因此，同时传播电子和原子核的耦合运动方程似乎是必要的。所应用的计算模型能够在允许直接模拟自然时间尺度上的电荷转移事件的同时，捕捉反应动力学和热力学的本质。
