Protein dynamics and hydrogen tunneling in enzyme catalysis

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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.