Abdizadeh Haleh, Guven Gokce, Atilgan Ali Rana, Atilgan Canan
a Faculty of Engineering and Natural Sciences , Sabanci University , Tuzla , Istanbul , Turkey.
J Enzyme Inhib Med Chem. 2015 Dec;30(6):867-73. doi: 10.3109/14756366.2014.979345. Epub 2015 Feb 3.
Can one infer the amino acids of the enzymes that are responsible for the stability or the level of the catalytic activity by computationally experimenting on the inhibited enzyme in the enzyme-inhibitor complex? In this article, we answer this question positively both by designing molecular dynamics simulations and by devising coarse-grained methodologies on the subtilisin serine protease. Both methodologies are based on the cross-correlations of the fluctuations of the residues, obtained either by monitoring the trajectories from the simulation or by constructing the inverse Laplacian of the elastic network model, of the complex. A perturbation scanning is applied to the complex using these correlations. The results indicate that the two methods almost point out the same regions on the flexible of the enzyme. These regions are: (i) 50-61, (ii) 155-164 and (iii) 192-194, all of which are designated to be important by experimental studies in the literature.
能否通过对酶-抑制剂复合物中被抑制的酶进行计算实验，推断出负责稳定性或催化活性水平的酶的氨基酸序列？在本文中，我们通过设计分子动力学模拟以及在枯草杆菌蛋白酶丝氨酸蛋白酶上设计粗粒度方法，对这个问题给出了肯定的答案。这两种方法都基于通过监测模拟轨迹或构建复合物弹性网络模型的逆拉普拉斯算子获得的残基波动的互相关性。使用这些相关性对复合物进行微扰扫描。结果表明，这两种方法几乎指出了酶柔性部分上相同的区域。这些区域是：(i) 50 - 61，(ii) 155 - 164和(iii) 192 - 194，所有这些区域在文献中的实验研究中都被认为是重要的。
