Water can act as catalyst is perhaps the most intriguing property reported of this molecule in the last decade. However, despite being an integral part of many enzyme structures, the role of water in catalyzing enzymatic reactions remains sparsely studied. In a recent study, we have shown that the epoxide ring opening in aspartate proteases follows a two-step process involving water. In this work, we attempt to unravel the electronic basis of the co-catalytic role of water in the epoxide ring opening reaction by employing high-level quantum mechanical calculations at M06-2X/6-31+G(d,p) level of accuracy. Our computed electron density and its reduced gradient show that water anchor the reactant molecules through strong H-bond bridges. In addition, the strong ionizing power of water allows better charge delocalization to stabilize the transition states and oxyanion intermediate. Electrostatic analyses suggest greater charge transfer from the aspartates to the epoxide in the transition state, which is found to be exergonic in nature rendering a low-barrier reaction compared to a control system where water was omitted in the reaction field. This elucidated mechanism at electronic level could promote further research to search for the co-catalytic role of water in other enzymes.

在过去的十年中，水可以作为催化剂，可能是该分子最引人入胜的特性。然而，尽管水是许多酶结构的组成部分，但仍很少研究水在催化酶促反应中的作用。在最近的研究中，我们表明天冬氨酸蛋白酶中的环氧化物开环遵循两步过程，其中涉及水。在这项工作中，我们试图通过在M06-2X / 6-31 + G（d，p）的水平上进行高级量子力学计算，来揭示水在环氧化物开环反应中的助催化作用的电子基础。准确性。我们计算出的电子密度及其减小的梯度表明，水通过牢固的H键桥固定了反应物分子。此外，水的强大电离能力可实现更好的电荷离域，以稳定过渡态和氧阴离子中间体。静电分析表明，在过渡态下，从天冬氨酸到环氧化物的电荷转移更多，与在反应场中省略水的对照体系相比，该化合物本质上具有能垒性，因此具有较低的势垒反应。在电子水平上阐明的机制可以促进进一步的研究，以寻找水在其他酶中的共催化作用。