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

催化剂、分子或材料可以提高反应速率而不被消耗，对生命和我们的生活方式至关重要。例如，糖苷键存在于整个生物物质（例如，碳水化合物或DNA）中，并且非常不易通过与水的反应被破坏（称为水解裂解）。事实上，据估计，在标准条件下，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样的水解裂解。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”速率常数水解这种键！此外，据估计，美国化学和制药工业90%以上的化学制造都需要使用催化剂，以实现经济生产或生产治疗药物制造经常需要的高度特异性化学前体。然而，目前许多工业催化剂被比作催化“锤子/刀”：它们需要大量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”：它们在非常温和的条件下发挥最佳作用，就像我们体内发现的那样，通常具有高度的靶向性，产生很少或不产生副产物。计算化学是利用计算机来模拟和预测化学物质的化学性质。它已经成为研究化学问题的一个非常强大和无价的工具。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的非凡催化能力背后的基本原理。这样的见解和理解可以设计出新的、更有效的、更环保的催化剂，用于工业过程和我们的日常生活。此外，它可以导致新的，更有效的治疗药物和其他医疗效益的发展。

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.