Department of Chemistry , Federal University of Paraíba , Cidade Universitária, João Pessoa , Paraíba 58051-085 , Brazil.
Department of Fundamental Chemistry , Federal University of Pernambuco , Cidade Universitária, Recife , Pernambuco 50670-901 , Brazil.
J Chem Inf Model. 2020 Feb 24;60(2):578-591. doi: 10.1021/acs.jcim.9b00860. Epub 2020 Jan 10.
In general, computational simulations of enzymatic catalysis processes are thermodynamic and structural surveys to complement experimental studies, requiring high level computational methods to match accurate energy values. In the present work, we propose the usage of reactivity descriptors, theoretical quantities calculated from the electronic structure, to characterize enzymatic catalysis outlining its reaction profile using low-level computational methods, such as semiempirical Hamiltonians. We simulate three enzymatic reactions paths, one containing two reaction coordinates and without prior computational study performed, and calculate the reactivity descriptors for all obtained structures. We observed that the active site local hardness does not change substantially, even more so for the amino-acid residues that are said to stabilize the reaction structures. This corroborates with the theory that activation energy lowering is caused by the electrostatic environment of the active sites. Also, for the quantities describing the atom electrophilicity and nucleophilicity, we observed abrupt changes along the reaction coordinates, which also shows the enzyme participation as a reactant in the catalyzed reaction. We expect that such electronic structure analysis allows the expedient proposition and/or prediction of new mechanisms, providing chemical characterization of the enzyme active sites, thus hastening the process of transforming the resolved protein three-dimensional structures in catalytic information.
一般来说，酶催化过程的计算模拟是对实验研究的热力学和结构调查的补充，需要使用高级计算方法来匹配准确的能量值。在本工作中，我们提出使用反应性描述符，即从电子结构计算得出的理论量，来描述酶催化作用，使用低级计算方法（如半经验哈密顿量）概述其反应轮廓。我们模拟了三条酶促反应路径，其中一条包含两个反应坐标，并且没有事先进行计算研究，并计算了所有获得结构的反应性描述符。我们观察到，活性部位局部硬度没有实质性变化，对于据说稳定反应结构的氨基酸残基更是如此。这证实了降低活化能是由活性部位的静电环境引起的理论。此外，对于描述原子亲电性和亲核性的量，我们观察到沿反应坐标发生了突然变化，这也表明酶作为反应物参与了催化反应。我们期望这种电子结构分析能够快速提出和/或预测新的机制，提供酶活性部位的化学特征，从而加速将解析的蛋白质三维结构转化为催化信息的过程。
