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首页> 外文期刊>The journal of physical chemistry, A. Molecules, spectroscopy, kinetics, environment, & general theory >Predicting mutation-induced stark shifts in the active site of a protein with a polarized force field
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Predicting mutation-induced stark shifts in the active site of a protein with a polarized force field

机译：预测具有极化力场的蛋白质活性位点中突变诱发的明显转变

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摘要

The electric field inside a protein has a significant effect on the protein structure, function, and dynamics. Recent experimental developments have offered a direct approach to measure the electric field by utilizing a nitrile-containing inhibitor as a probe that can deliver a unique vibration to the specific site of interest in the protein. The observed frequency shift of the nitrile stretching vibration exhibits a linear dependence on the electric field at the nitrile site, thus providing a direct measurement of the relative electric field. In the present work, molecular dynamics simulations were carried out to compute the electric field shift in human aldose reductase (hALR2) using a polarized protein-specific charge (PPC) model derived from fragment-based quantum-chemistry calculations in implicit solvent. Calculated changes of electric field in the active site of hALR2 between the wild type and mutants were directly compared with measured vibrational frequency shifts (Stark shifts). Our study demonstrates that the Stark shifts calculated using the PPC model are in much better agreement with the experimental data than widely used nonpolarizable force fields, indicating that the electronic polarization effect is important for the accurate prediction of changes in the electric field inside proteins.
机译：蛋白质内部的电场会对蛋白质的结构，功能和动力学产生重大影响。最近的实验发展提供了一种直接的方法来测量电场，方法是利用含腈的抑制剂作为探针，该探针可以将独特的振动传递到蛋白质中特定的目标位点。所观察到的腈拉伸振动的频移表现出对腈位置处电场的线性依赖性，因此可以直接测量相对电场。在目前的工作中，使用分子动力学模拟来计算人醛糖还原酶（hALR2）中的电场位移，该方法使用的是极化蛋白特异性电荷（PPC）模型，该模型是基于隐式溶剂中基于片段的量子化学计算得出的。将野生型和突变型之间的hALR2活性位点中计算出的电场变化直接与测得的振动频率位移（斯塔克位移）进行比较。我们的研究表明，与广泛使用的不可极化力场相比，使用PPC模型计算的Stark位移与实验数据更加吻合，这表明电子极化效应对于准确预测蛋白质内部电场的变化非常重要。

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