An insight into the general relationship between the three dimensional structures of enzymes and their electronic wave functions: Implication for the prediction of functional sites of enzymes
An insight into the general relationship between the three dimensional structures of enzymes and their electronic wave functions: Implication for the prediction of functional sites of enzymes
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DOI：
10.1002/prot.21865
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发表时间：
2008-06-01
影响因子：
2.9
通讯作者：
Sakurai, M.
中科院分区：
文献类型：
--
作者：
Fukushima, K.;Wada, M.;Sakurai, M.
在这项研究中，我们探讨了酶的三维（3D）结构和它们的电子波函数之间的一般关系。此外，我们开发了一种方法，用于预测其功能的重要网站。为此，我们首先进行了线性标度的分子轨道计算112非冗余，非同源酶与已知的结构和功能。结果表明，根据电子离域的程度，这些酶的正则分子轨道（MO）可以分为三组：高度定域轨道（A组）、电子几乎分布在整个分子上的高度离域轨道（B组）和中度离域轨道（Q组）。属于A组的MO位于HOMO-LUMO带隙附近，从而包括给定酶的前沿轨道。我们推测B族的分子轨道在稳定酶的三维结构中起作用，而C族的分子轨道有助于构建酶的共价键框架。接下来，我们研究了酶的前沿轨道是否可以用于识别其潜在的功能位点。因此，我们发现，前线轨道的112种酶有很高的倾向，被共定位与已知的功能位点，特别是当酶水合。当Glu或Asp是功能性位点残基时，这种倾向显示为显著的。在这些结果的基础上，我们最后提出了一个预测酶的功能位点的协议。
In this study, we explored the general relationship between the three-dimensional (3D) structures of enzymes and their electronic wave functions. Furthermore, we developed a method for the prediction of their functionally important sites. For this purpose, we first performed linear-scaling molecular orbital calculations for 112 nonredundant, non-homologous enzymes with known structure and function. In consequence, we showed that the canonical molecular orbitals (MOs) of the enzymes could be classified into three groups according to the degree of electron delocalization: highly localized orbitals (Group A), highly delocalized orbitals whose electrons are distributed over almost the whole molecule (Group B), and moderately delocalized orbitals (Group Q. The MOs belonging to Group A are located near the HOMO-LUMO band gap, and thereby include the frontier orbitals of a given enzyme. We inferred that the MOs of Group B play a role in stabilizing the 3D structure of the enzyme, while those of Group C contribute to constructing the covalent bond framework of the enzyme. Next, we investigated whether the frontier orbitals of enzymes could be used for identifying their potential functional sites. As a result, we found that the frontier orbitals of the 112 enzymes have a high propensity to be colocalized with the known functional sites, especially when the enzymes are hydrated. Such a propensity is shown to be remarkable when Glu or Asp is a functional site residue. On the basis of these results, we finally propose a protocol for the prediction of functional sites of enzymes.