腺苷酸激酶催化ATP和AMP转化为ADP过程中LID和NMP结构域运动之间的动态耦合
Dynamic coupling between the LID and NMP domain motions in the catalytic conversion of ATP and AMP to ADP by adenylate kinase
摘要：
腺苷酸激酶（ADK）将ATP和AMP催化转化为ADP涉及大幅度的配体诱导的结构域运动，涉及在重复的催化循环期间LID和NMP结构域的打开和关闭。我们发现并分析了一个有趣的动力学耦合运动的两个域在开放期间，使用大尺度原子分子动力学轨迹分析，协方差分析和多维自由能计算与明确的水。最初，LID域必须在NMP域可以开始打开之前打开一定量。动态相关图显示LID和NMP结构域之间的有趣交叉峰，这表明它们之间存在相关运动。这也反映在我们计算的二维自由能表面轮廓图中，该图具有有趣的椭圆形状，揭示了LID域和NMP域的开放之间的强相关性。由于与水的相互作用，我们的LID域运动的自由能表面是粗糙的，并且在所观察到的RMSD变化及其波动时间关联函数中，粗糙的特征是明显的。我们发展了一个相关动力学无序型理论模型来解释ADK中两个畴运动之间的动力学耦合。我们的模型正确地再现了模拟中观察到的互相关的几个功能。
英文摘要：
The catalytic conversion of ATP and AMP to ADP by adenylate kinase (ADK) involves large amplitude, ligand induced domain motions, involving the opening and the closing of LID and NMP domains, during the repeated catalytic cycle. We discover and analyze an interesting dynamical coupling between the motions of the two domains during the opening, using large scale atomistic molecular dynamics trajectory analysis, covariance analysis and multi-dimensional free energy calculations with explicit water. Initially, the LID domain must open by a certain amount before the NMP domain can begin to open. Dynamical correlation map shows interesting cross-peak between LID and NMP domain which suggests the presence of correlated motion between them. This is also reflected in our calculated two dimensional free energy surface contour diagram which has an interesting elliptic shape, revealing a strong correlation between the opening of the LID domain and that of the NMP domain. Our free energy surface of the LID domain motion is rugged due to interaction with water and the signature of ruggedness is evident in the observed RMSD variation and its fluctuation time correlation functions. We develop a correlated dynamical disorder type theoretical model to explain the observed dynamic coupling between the motions of the two domains in ADK. Our model correctly reproduces several features of the cross-correlation observed in simulations.
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