Molecular dynamics of apo-adenylate kinase: A principal component analysis
Molecular dynamics of apo-adenylate kinase: A principal component analysis
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DOI：
10.1021/jp061976m
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发表时间：
2006-06-29
影响因子：
3.3
通讯作者：
Cukier, Robert I.
中科院分区：
文献类型：
--
作者：
Lou, Hongfeng;Cukier, Robert I.
用分子动力学方法研究了来自大肠杆菌的腺苷酸激酶(AKE)。当AKE的开放形式关闭其底物AMP和Mg2+-ATP时，它的LID和AMP结合域经历了大规模的运动。第三个领域，核心，在关闭期间相对稳定。使用主成分分析方法对得到的轨迹进行分析，该方法将原子运动分解成按其对总蛋白质波动的递减贡献排序的模式。在303K(正常温度)和500K(高温)下的模拟表明，在这两个温度下，前三个模占总涨落的70%。对这三种模式贡献最大的残基集中在LID和AMP结合区域。对正常T模式的分析表明，LID和AMP结合结构域具有广泛的构象分布，表明AKE旨在为其底物提供大量的构象。高T结果表明，盖子最初向核心关闭。随后，盖子旋转到不同于在底物结合的AKE中观察到的新的稳定构象。这些结果是在实验数据的背景下讨论的，这些数据表明腺苷酸激酶确实在溶液中采样不止一个构象状态，并且每个构象状态都经历了很大的波动。建议了一对残基用于标记，这将有助于通过能量转移实验监测距离波动。
Adenylate kinase from E. coli (AKE) is studied with molecular dynamics. AKE undergoes large-scale motions of its Lid and AMP-binding domains when its open form closes over its substrates, AMP and Mg2+-ATP. The third domain, the Core, is relatively stable during closing. The resulting trajectory is analyzed with a principal component analysis method that decomposes the atom motions into modes ordered by their decreasing contributions to the total protein fluctuation. Simulations at 303 K (normal T) and 500 K (high T) reveal that at both temperatures the first thee modes account for 70% of the total fluctuation. The residues that contribute the most to these three modes are concentrated in the Lid and AMP-binding domains. Analysis of the normal T modes indicates that the Lid and AMP-binding domains sample a broad distribution of conformations indicating that AKE is designed to provide its substrates with a large set of conformations. The high T results show that the Lid initially closes toward the Core. Subsequently, the Lid rotates to a new stable conformation that is different from what is observed in the substrate-bound AKE. These results are discussed in the context of experimental data that indicate that adenylate kinases do sample more than one conformational state in solution and that each of these conformational states undergoes substantial fluctuations. A pair of residues is suggested for labeling that would be useful for monitoring distance fluctuations by energy transfer experiments.