Simulation of tunneling in enzyme catalysis by combining a biased propagation approach and the quantum classical path method: application to lipoxygenase.
Simulation of tunneling in enzyme catalysis by combining a biased propagation approach and the quantum classical path method: application to lipoxygenase.
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通过结合偏置传播方法和量子经典路径方法来模拟酶催化中的隧道效应：在脂氧合酶中的应用。
DOI：
10.1021/jp0758420
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Warshel,Arieh
中科院分区：
文献类型：
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作者：
Mavri,Janez;Liu,Hanbin;Olsson,MatsHM;Warshel,Arieh
探索了用波函数传播方法模拟酶中同位素效应的能力，重点研究了大豆脂氧合酶-1(SLO-1)的大H/D动力学同位素效应。H/D动力学同位素效应(Kie)由氢和氢转移的速率常数之比计算得到。根据H和D核波函数的时间历程计算了速率常数。传播是使用从蛋白质中反应系统的整个多维表面产生的一维质子势来完成的。这些截面是在SLO-1的经典经验价键(EVB)分子动力学模拟中获得的。由于传播需要极长的时间来处理现实的激活障碍，因此使用有效的偏置方法是必不可少的。因此，我们在这里发展了一种方法，它使用经典的量子路径(QCP)方法来评估与偏置势相关的量子自由能变化。这种方法为完整的QCP模拟和其他当前模拟蛋白质中的同位素效应的方法提供了一种有趣的替代方法。特别是，这种方法可以用来评估量子力学传输因子或其他动力学效应，同时仍然可以获得由于QCP修正而产生的可靠的量子化激活自由能。
The ability of using wave function propagation approaches to simulate isotope effects in enzymes is explored, focusing on the large H/D kinetic isotope effect of soybean lipoxygenase-1 (SLO-1). The H/D kinetic isotope effect (KIE) is calculated as the ratio of the rate constants for hydrogen and deuterium transfer. The rate constants are calculated from the time course of the H and D nuclear wave functions. The propagations are done using one-dimensional proton potentials generated as sections from the full multidimensional surface of the reacting system in the protein. The sections are obtained during a classical empirical valence bond (EVB) molecular dynamics simulation of SLO-1. Since the propagations require an extremely long time for treating realistic activation barriers, it is essential to use an effective biasing approach. Thus, we develop here an approach that uses the classical quantum path (QCP) method to evaluate the quantum free energy change associated with the biasing potential. This approach provides an interesting alternative to full QCP simulations and to other current approaches for simulating isotope effects in proteins. In particular, this approach can be used to evaluate the quantum mechanical transmission factor or other dynamical effects, while still obtaining reliable quantized activation free energies due to the QCP correction.