Nutt David R, Karplus Martin, Meuwly Markus
Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland.
J Phys Chem B. 2005 Nov 10;109(44):21118-25. doi: 10.1021/jp0523975.
Ligands such as CO, O(2), or NO are involved in the biological function of myoglobin. Here we investigate the energetics and dynamics of NO interacting with the Fe(II) heme group in native myoglobin using ab initio and molecular dynamics simulations. At the global minimum of the ab initio potential energy surface (PES), the binding energy of 23.4 kcal/mol and the Fe-NO structure compare well with the experimental results. Interestingly, the PES is found to exhibit two minima: There exists a metastable, linear Fe-O-N minimum in addition to the known, bent Fe-N-O global minimum conformation. Moreover, the T-shaped configuration is found to be a saddle point, in contrast to the corresponding minimum for NO interacting with Fe(III). To use the ab initio results for finite temperature molecular dynamics simulations, an analytical function was fitted to represent the Fe-NO interaction. The simulations show that the secondary minimum is dynamically stable up to 250 K and has a lifetime of several hundred picoseconds at 300 K. The difference in the topology of the heme-NO PES from that assumed previously (one deep, single Fe-NO minimum) suggests that it is important to use the full PES for a quantitative understanding of this system. Why the metastable state has not been observed in the many spectroscopic studies of myoglobin interacting with NO is discussed, and possible approaches to finding it are outlined.
一氧化碳、氧气或一氧化氮等配体参与了肌红蛋白的生物学功能。在此，我们使用从头算和分子动力学模拟研究了一氧化氮与天然肌红蛋白中Fe(II)血红素基团相互作用的能量学和动力学。在从头算势能面（PES）的全局最小值处，23.4千卡/摩尔的结合能以及Fe-NO结构与实验结果吻合良好。有趣的是，发现PES呈现出两个最小值：除了已知的弯曲的Fe-N-O全局最小构象外，还存在一个亚稳的线性Fe-O-N最小值。此外，发现T形构型是一个鞍点，这与一氧化氮与Fe(III)相互作用时相应的最小值情况相反。为了将从头算结果用于有限温度分子动力学模拟，拟合了一个解析函数来表示Fe-NO相互作用。模拟表明，次要最小值在高达250 K时动力学稳定，在300 K时具有几百皮秒的寿命。血红素-NO PES的拓扑结构与先前假设的（一个深的、单一的Fe-NO最小值）不同，这表明使用完整的PES对于定量理解该系统很重要。讨论了为何在许多肌红蛋白与一氧化氮相互作用的光谱研究中未观察到亚稳态，并概述了发现它的可能方法。
