应用广义活性指标预测酶催化反应的分子间活性

Prediction on molecular reactivity of enzymatic catalysis by the generalized reactivity descriptor

为了进一步验证广义活性指标的合理性与准确性,本文将其应用到了大分子生物体系中,结合局域硬软酸碱(HSAB)原理,研究酶催化反应的活性序列,即砷酸盐还原酶ArsC(1LJU10～17)和低分子量的磷酸盐还原酶LWMPTPase(1PNT12～18)分别亲核进攻砷酸盐和磷酸盐的所有形式(H3YO4/H2YO4-/HYO42-/YO43-,Y=As/P)的反应活性序列,其中,广义局域软度由有限差分近似下的从头计算B3LYP/6-311+G(d,p)方法和直接的ABEEMσπ方法获得.随着底物的负电荷不断增大,体系的整体软度和中心原子的局域软度均变得更软,砷酸盐及其还原酶也比磷酸盐及其还原酶要软.利用广义局域软度结合软度的匹配规则,可知随着底物负电荷的逐渐增加,原子个数较大的酶与底物之间的反应活性不断升高,并且-2价的阴离子(HAsO42-和HPO42-)能够在溶液中稳定存在.所预测的活性序列与实验所测得的结果是相一致的,可见,广义局域软度在预测分子间活性方面能够给出合理的预测.然而,原局域软度结合软度的匹配原则在预测接近真实体系的分子间活性的时候,却得到与实验相反的结果.

In order to further check the rationality and accuracy of the generalized reactivity descriptor, our main aim is applying it on the greater biological system. Hence, the reactivity sequences of the enzymatic catalysis of the nucleophile arsenate reductase （ArsC： 1LJU10-17） and low molecular weight phosphatase （LWMPTPase： 1PNT12-1 8） toward the neutral and all ionic forms of arsenate and phosphate （H3YO4/H2YO4/HYO42-/YO43-, Y=As/P） were investigated according to the generalized local softness combined with the local HSAB principle, where the generalized local softness was obtained by B3LYP/6-31 l＋G（d,p） method under the finite difference approximation and the ABEEMtr^r model. It can be seen that when the charge of the substrate increases, both the global softness of the system and the local softness of the central atom of the compound increase. And then, arsenate and the ArsC are also softer than phosphate and the LWMPTPase, respectively. When the model molecule is close to the actual system, through the negative charge rising, the reaction reactivities gradually ascend by the generalized local softness combined with the softness matching procedure, and then the di-anions （HAsO^- and HPO]-） are the stabilized species in the solvent. Therefore, these results are in agreement with the experimental results, and the generalized local softness can give a successful prediction on the molecular reactivity. However, the results from the normal local softness combined with the matching criterion for predicting the intermolecular reactivity of these biological systems are not in line with the experimental results.