Elucidating the Power of Scalpels of Catalysis: Computational and Theoretical Investigations on Biocatalytic Systems

催化剂、分子或材料可以加快反应速度而不被消耗，它们对生命和我们的生活方式都是必不可少的。例如，糖苷键存在于整个生物体(如碳水化合物或DNA)中，并且非常不易与水反应而断裂(称为水解性裂解)。事实上，据估计，在标准条件下，一条纤维素链中一半的糖苷键需要大约500万年的时间才能发生这种水解性断裂。然而，在细胞中，被称为糖苷酶的酶能够以高达1000 S-1的‘生命可持续’速率常数来降解这种键！此外，据估计，美国化学工业和制药业90%以上的化学制造需要使用催化剂，以实现经济生产或生产治疗药物制造经常需要的高度特定的化学前体。然而，许多当前的工业催化剂被比作催化“锤子/刀”：它们需要巨大的能量来合成和发挥作用，并产生不需要的、通常是有毒的副产品。相比之下，酶等生物催化剂被认为类似于“催化手术刀”：它们在我们体内发现的非常温和的条件下工作得最好，通常是高度靶标特异性的，产生的副产品很少或根本没有。计算化学是使用计算机来模拟和预测化学物种的化学和性质。它已经确立了自己作为一个令人难以置信的强大和宝贵的工具来研究化学问题。这项研究计划的目标是了解几种对生命至关重要的生物催化剂非凡催化能力背后的基本原理。这样的洞察力和理解可以设计出新的、更有效和更环保的催化剂，用于工业过程和我们的日常生活。此外，它还可以带来新的、更有效的治疗药物的开发和其他医疗益处。

Catalysts, molecules or materials that enhance the rates of reactions without themselves being consumed, are essential for life and our way of life. For example, glycosidic bonds are found throughout living matter (e.g., carbohydrates or DNA) and are remarkably resistant to being broken via reaction with water (known as hydrolytic cleavage). Indeed, it has been estimated that, under standard conditions, it would take approximately 5 million years for half of the glycosidic bonds in a strand of cellulose to undergo such hydrolytic cleavage. However, in cells, enzymes known as glycosidases are able to hydrolyse such bonds with 'life-sustainable' rate constants of up to 1000 s-1! In addition, it has been estimated that more than 90% of chemical manufacturing by the US chemical and pharmaceutical industry requires the use of catalysts in order to achieve economical production or to produce highly-specific chemical precursors as often required for therapeutic drug manufacturing.However, many current industrial catalysts are likened to catalytic "hammers/knives": they require tremendous amounts of energy to synthesize and to then function, and produce unwanted, often toxic byproducts. In contrast, biocatalysts such as enzymes are said to be akin to "catalytic scalpels": they work best under very mild conditions as found in our bodies, are usually highly target-specific and produce minimal or no byproducts. Computational chemistry is the use of computers to model and predict the chemistry and properties of chemical species. It has established itself as an incredibly powerful and invaluable tool for investigating chemical problems. The goal of this research program is to understand the fundamental principles behind the remarkable catalytic power of several types of life-critical biocatalysts. Such insights and understanding can enable the design of new, more effective and greener catalysts for use in industrial process and our everyday lives. In addition, it can lead to development of new, more effective therapeutic drugs and other medical benefits.