Molecular dynamics simulations of the enzyme Cu, Zn superoxide dismutase
Molecular dynamics simulations of the enzyme Cu, Zn superoxide dismutase
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DOI：
10.1021/jp0568551
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发表时间：
2006-08-24
影响因子：
3.3
通讯作者：
Ramos, Maria J.
中科院分区：
文献类型：
--
作者：
Branco, Ricardo J. F.;Fernandes, Pedro A.;Ramos, Maria J.
酶Cu，Zn超氧化物歧化酶（Cu，Zn-SOD）是一种普遍存在的氧化还原酶，其负责细胞防御由超氧化物自由基的高毒性引起的氧化应激，并且还与一些常见的肌萎缩侧索硬化症病例有关。本文导出了Cu，Zn-SOD活性中心的分子力学参数。之后，在水环境中进行了广泛的分子动力学模拟。所获得的结果揭示了进一步的光的结构灵活性的骨干，其中的活性位点是嵌套的，和溶剂化壳层占用。相对较小的骨架偏差（由低于1.0埃的均方根偏差表示）证实了参数的准确性。溶剂壳分析表明，第一溶剂化壳位于离铜离子约5埃处，产生具有足够空间以容纳超氧自由基的空腔。低停留时间意味着两个溶剂化壳层中的水分子的高置换率与该催化机制的效率一致。现在可以使用ONIOM方法进行混合研究，以评估明确纳入整个系统的机制影响。
The enzyme Cu, Zn superoxide dismutase (Cu, Zn-SOD) is a ubiquitous oxireductase, which is responsible for the cellular defense against oxidative stress caused by the high toxicity of the superoxide radical, and has been also linked to some cases of familiar amyotrophic lateral sclerosis. In the present study a set of molecular mechanics parameters for the active site of Cu, Zn-SOD has been derived. Afterward, an extensive molecular dynamics simulation has been carried out in an aqueous environment. The obtained results shed a further light on the structural flexibility of the backbone, where the active site is nested, and the solvation shell occupancy. The relatively small backbone deviation, shown by a root-mean-square deviation below 1.0 angstrom, confirms the accuracy of the parameters. The solvent shell analysis has shown that the first solvation shell is located at about 5 angstrom from the copper ion, generating an empty cavity with enough space to accommodate the superoxide radical. The low residence time means that a high permutation rate of water molecules in both solvation shells is consistent with the efficiency of this catalytic mechanism. Hybrid studies using ONIOM methodologies can now be done to evaluate the mechanistic implications of the explicit inclusion of the whole system.