Department of Chemistry, School of Natural Sciences, Shiv Nadar University, Delhi-NCR, 201314, India.
Center for Informatics, Department of Chemistry, School of Natural Sciences, Shiv Nadar University, Delhi-NCR, 201314, India.
Phys Chem Chem Phys. 2022 Jan 26;24(4):1974-1981. doi: 10.1039/d1cp03978d.
The current theoretical perception of enzymatic activity is highly reliant on the determination of the activation energy of the reactions, which is often calculated using computationally demanding quantum mechanical calculations. With the ever-increasing use of bioengineering techniques that produce too many variants of the same enzyme, a fast and accurate way to study the relative efficiency of enzymes is currently in high demand. Here, we propose the local electric field (LEF) of the enzyme along the reaction axis as a descriptor for the enzymatic activity using the example of chorismate mutase in its native form and several variants (R90A, R90G, and R90K/C88S). The study shows a direct correlation between the calculated enzymatic EF and the enzymatic activity for all the complexes. MD simulations of the Michaelis complex and the transition state analog (TSA) show a stabilizing force on the TSA due to the enzymatic EF. QM/MM and QM-only DFT calculations in the presence of an external electric field (EEF) oriented along the reaction axis show that the electric field can interact with the dipole moment of the TS, thereby stabilizing it and thus lowering the activation energy.
目前对酶活性的理论认识高度依赖于对反应活化能的测定，而这通常需要使用计算要求很高的量子力学计算来计算。随着生物工程技术的应用越来越多，这些技术会产生大量相同酶的变体，因此，目前非常需要一种快速而准确的方法来研究酶的相对效率。在这里，我们以天然形式和几种变体（R90A、R90G 和 R90K/C88S）的色氨酸合酶为例，提出了沿反应轴的酶局部电场（LEF）作为酶活性的描述符。该研究表明，对于所有复合物，计算出的酶 EF 与酶活性之间存在直接相关性。迈克尔is 复合物和过渡态类似物（TSA）的 MD 模拟显示，由于酶 EF，TSA 上存在稳定力。在沿反应轴定向的外部电场（EEF）存在的情况下进行的 QM/MM 和 QM 仅 DFT 计算表明，电场可以与 TS 的偶极矩相互作用，从而稳定它并降低活化能。
