Protein dynamics and hydrogen tunneling in enzyme catalysis

该奖项由化学部实验物理化学计划和生物学理事会分子和细胞生物科学部分子生物化学计划资助，Amnon Kohen教授。爱荷华州大学的教授和他的研究生和本科生同事将继续进行旨在更好地理解酶如何激活共价键的研究。 这项研究的最终目标是了解酶动力学如何影响反应性。 具体来说，他们将研究三个模型系统：二氢叶酸还原酶，乙醇脱氢酶和胸苷酸合成酶。 他们研究这些酶的方法是通过对酶进行特定的突变，以已知的方式微妙地改变酶的结构，并将这些结构变化与反应性的变化相关联。酶在生物学，医学和商业中无处不在。 像科恩教授和他的团队这样的研究的最终目的是获得对生物系统如何进行重要化学反应的机械见解。 这将阐明进化在精炼键激活中的作用，量子现象（轻原子隧穿）在生物学中的作用，并将使我们更好地理解酶的全局结构-动力学-功能关系，这将对社会领域产生广泛的影响，其中设计酶以有用的方式工作的能力很重要。 除了这项工作的更广泛的科学影响外，科恩教授将继续招募、指导和教育一批不同的年轻科学家，从事物理科学和生物科学之间的科学研究。

In this award, funded by the Experimental Physical Chemistry Program of the Chemistry Division and the Molecular Biochemistry Program of the Molecular and Cellular Biosciences Division of the Biology Directorate, Prof. Amnon Kohen. of the University of Iowa and his graduate and undergraduate student colleagues will pursue studies aimed at developing a better understanding of how enzymes activate covalent bonds. The ultimate goal of this research is to understand how enzyme dynamics influence reactivity. Specifically, they will study three model systems: Dihydrofolate reductase, alcohol dehydrogenase and thymidylate synthase. Their approach to studying these enzymes is through making specific mutations to the enzyme that subtly change the enzyme structure in known ways and correlating these structural changes with changes in reactivity.Enzymes are ubiquitous in biology, medicine and commerce. The ultimate aims of research like that of Prof. Kohen and his group is to gain a mechanistic insight into how biological systems do important chemistries. This will shed light on the role of evolution in refining bond activation, the role of quantum phenomena (light atom tunneling) in biology, and will move us towards a better understanding of Global Structure-Dynamics-Function relationships in enzymes, which will have a broad impact in areas of society where the ability to design enzymes to work in useful ways is important. Besides the broader scientific impacts of this work, Prof. Kohen will continue to recruit, mentor and educate a diverse group of young scientists in science that lies at the interface of the physical and biological sciences.