Prof. Amnon Kohen, from the University of Iowa, seeks to gain a better understanding of how enzymes activate covalent bonds through a study of C-H bond activation that combines methods of experimental and computational physical chemistry, biochemistry, and molecular biology. The proposed research will examine the roles of protein dynamics, coupled motion, and hydrogen tunneling in enzyme catalysis. Specific aims of the research and outreach plans include: (i) examination of physical features of enzyme catalyzed H-transfer as imposed by the active site, (ii) elucidation of a proposed network of coupled dynamics across the protein through kinetic and dynamic methods; (iii) analysis of the nature of H-transfer in the context of enzyme evolution; and (iv) outreach activities that will enhance scientific research and science awareness in the general public.
The proposed project will address fundamental aspects of catalytic C-H bond activation. Tools to be developed utilize isotopic labeling of ubiquitous cofactors, and thus will be useful for studying many enzymes in a number of laboratories in this country and abroad. The concepts to be tested will impact both chemistry and biology, and may impact rational drug design, biomimetic catalyst design, and understanding of evolution at the molecular level.
The research and pedagogical activities will involve a broad range of institutions, from K-12 to research universities. At the elementary and middle school levels, these activities will boost the proportion of students who may choose science electives in high school (that is, potential future scientists). They will also encourage students who may choose non-science careers (such as future policy makers and the general public) to adopt a sympathetic perspective on science, as well as a better understanding of the critical role science plays in human well-being. Cooperative efforts with Colleges with small research programs will broaden the pool of prospective Ph.D. students.
Moreover, the projects are designed to enable involvement of a diverse cohort of students. To this end, efforts to recruit, train, and educate students from underrepresented groups will continue. In the last four years Dr. Kohen has had five minority students working with his group. Additionally, both men and women are equally represented in Dr. Kohen's group, and students come from very diverse backgrounds.
The findings, methods, and ideas originating from this project will be disseminated by means of publications and conference presentations, useful computer programs will be posted on-line free of charge, and experimental data will be made available to any researcher interested in analyzing similar chemical and biological systems.
This project is jointly supported by the Chemistry of Life Processes program in the Chemistry Division and the Biomolecular Dynamics, Structure and Function Cluster in the Division of Molecular and Cellular Biosciences.
