College of Physics and Electronics, Shandong Normal University, Jinan 250014, China.
Int J Mol Sci. 2021 May 29;22(11):5854. doi: 10.3390/ijms22115854.
Enzymes play a fundamental role in many biological processes. We present a theoretical approach to investigate the catalytic power of the haloalkane dehalogenase reaction with 1,2-dichloroethane. By removing the three main active-site residues one by one from haloalkane dehalogenase, we found two reactive descriptors: one descriptor is the distance difference between the breaking bond and the forming bond, and the other is the charge difference between the transition state and the reactant complex. Both descriptors scale linearly with the reactive barriers, with the three-residue case having the smallest barrier and the zero-residue case having the largest. The results demonstrate that, as the number of residues increases, the catalytic power increases. The predicted free energy barriers using the two descriptors of this reaction in water are 23.1 and 24.2 kcal/mol, both larger than the ones with any residues, indicating that the water solvent hinders the reactivity. Both predicted barrier heights agree well with the calculated one at 25.2 kcal/mol using a quantum mechanics and molecular dynamics approach, and also agree well with the experimental result at 26.0 kcal/mol. This study shows that reactive descriptors can also be used to describe and predict the catalytic performance for enzyme catalysis.
酶在许多生物过程中起着至关重要的作用。我们提出了一种理论方法来研究 1,2-二氯乙烷的卤代烷脱卤酶反应的催化能力。通过逐一去除卤代烷脱卤酶的三个主要活性位点残基，我们发现了两个反应性描述符：一个描述符是断裂键和形成键之间的距离差，另一个是过渡态和反应物络合物之间的电荷差。这两个描述符与反应性屏障呈线性关系，三残基情况的屏障最小，零残基情况的屏障最大。结果表明，随着残基数目的增加，催化能力增强。使用该反应的两个描述符在水中预测的自由能屏障分别为 23.1 和 24.2 kcal/mol，均大于任何残基的情况，表明水溶剂阻碍了反应性。这两个预测的势垒高度与使用量子力学和分子动力学方法计算的 25.2 kcal/mol 的结果非常吻合，也与实验结果 26.0 kcal/mol 吻合良好。这项研究表明，反应性描述符也可用于描述和预测酶催化的催化性能。
