Phosphate ester hydrolysis is fundamental to many life processes, and has been the topic of substantial experimental and computational research effort. However, even the simplest of phosphate esters can be hydrolyzed through multiple possible pathways that can be difficult to distinguish between, either experimentally, or computationally. Therefore, the mechanisms of both the enzymatic and non-enzymatic reactions have been historically controversial. In the present contribution, we highlight a number of technical issues involved in reliably modeling these computationally challenging reactions, as well as proposing potential solutions. We also showcase examples of our own work in this area, discussing both the non-enzymatic reaction in aqueous solution, as well as insights obtained from the computational modeling of organophosphate hydrolysis and catalytic promiscuity amongst enzymes that catalyze phosphoryl transfer.

中文翻译：

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生物磷酸盐水解计算模型的挑战与进展

磷酸酯水解是许多生命过程的基础，并且一直是大量实验和计算研究工作的主题。但是，即使是最简单的磷酸酯，也可以通过多种可能的途径进行水解，这些途径在实验或计算上都难以区分。因此，酶促反应和非酶促反应的机制在历史上一直是有争议的。在当前的贡献中，我们重点介绍了在可靠地建模这些计算上具有挑战性的反应以及提出潜在解决方案方面涉及的许多技术问题。我们还展示了我们在这一领域的工作实例，讨论了水溶液中的非酶反应，