On the Induced- Fit Mechanism of Substrate- Enzyme Binding Structures of Nylon- Oligomer Hydrolase
On the Induced- Fit Mechanism of Substrate- Enzyme Binding Structures of Nylon- Oligomer Hydrolase
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DOI：
10.1002/jcc.23614
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发表时间：
2014-06-15
影响因子：
3
通讯作者：
Shigeta, Yasuteru
中科院分区：
文献类型：
--
作者：
Baba, Takeshi;Harada, Ryuhei;Shigeta, Yasuteru
我们提出了一个详细的计算调查的诱导适合运动在尼龙低聚物水解酶（NylB）底物结合。为了这个目的，我们诉诸最近推出的平行级联选择分子动力学方法，允许加速访问的一组构象变化，从开放到封闭状态的结构，形成酶-底物复合物在一个特定的诱导适合机制。结构调查的定量补充伞抽样算法内的自由能分析伴随着加权直方图分析。我们发现稳定化自由能约为1.4千卡/摩尔，而要克服的最高自由能势垒约为2.3千卡/摩尔。相反地，根据广义玻恩/表面积估计，底物结合的能量贡献约为20千卡/摩尔。这意味着一旦基底结合到NylB的打开状态，打开-闭合诱导配合运动就可能频繁发生。(c)2014 Wiley Periodicals，Inc.
We present a detailed computational investigation of the induced-fit motion in a nylon-oligomer hydrolase (NylB) upon substrate binding. To this aim, we resort on the recently introduced parallel cascade selection molecular dynamics approach, allowing for an accelerated access to the set of conformational changes from an open- to a closed-state structure to form the enzyme-substrate complex in a specific induce-fit mechanism. The structural investigation is quantitatively complemented by free energy analyses within the umbrella sampling algorithm accompanied by weighted histogram analysis. We find that the stabilization free energy is about 1.4 kcal/mol, whereas the highest free energy barrier to be overcome is about 2.3 kcal/mol. Conversely, the energetic contribution for the substrate binding is about 20 kcal/mol, as estimated from Generalized Born/Surface Area. This means that the open-close induced-fit motion could occur frequently once the substrate binds to the open state of NylB. (c) 2014 Wiley Periodicals, Inc.