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

阐明催化手术刀的威力：生物催化系统的计算和理论研究

• 批准号: 249955-2013
• 负责人: Gauld, James
• 金额: $ 2.48万
• 依托单位: University of Windsor
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570778
• 关键词: Elucidating; Power; Scalpels; Catalysis; Computational

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.

催化剂，分子或材料提高反应速率而不会消耗自身，对生活和我们的生活方式至关重要。例如，在整个生命物质（例如碳水化合物或DNA）中都发现糖苷键，并且对通过与水的反应（称为水解裂解）非常抗性。实际上，据估计，在标准条件下，一束纤维素中的糖苷键的一半将需要大约500万年才能进行这种水解裂解。然而，在细胞中，称为糖苷酶的酶能够用“可持续的”速率常数高达1000 s-1的键来水解此类键！此外，据估计，美国化学和制药行业的化学制造中有90％以上需要使用催化剂，以实现经济生产或经常生产具有治疗性药物制造所需的高度特异性化学前体。 但是，许多当前的工业催化剂被比作催化“锤子/刀具”：它们需要大量的能量才能合成，然后发挥作用，并产生不必要的，有毒的副产品。相比之下，据说酶等生物催化剂类似于“催化手术刀”：它们在我们体内发现的非常温和的条件下最有效，通常是高度靶标特异性的，并且最少或没有副产物。 计算化学是使用计算机来建模和预测化学物种的化学和特性。它已将自己确立为一种非常有力且宝贵的工具，用于研究化学问题。该研究计划的目的是了解几种类型的生命生命生物催化剂的显着催化能力背后的基本原理。这样的见解和理解可以使新的，更有效，更绿色的催化剂的设计用于工业过程和我们的日常生活。此外，它可能导致新的，更有效的治疗药物和其他医疗益处的发展。