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

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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.