Protein dynamics and hydrogen tunneling in enzymatic catalysis

来自爱荷华州大学的Amnon Kohen教授试图通过结合实验和计算物理化学、生物化学和分子生物学方法的C-H键活化研究，更好地了解酶如何活化共价键。拟议的研究将研究蛋白质动力学，耦合运动和氢隧道在酶催化中的作用。研究和推广计划的具体目标包括：（一）检查活性位点所施加的酶催化H-转移的物理特征，（二）通过动力学和动力学方法阐明跨蛋白质的耦合动力学拟议网络;（三）在酶进化的背景下分析H-转移的性质;及（iv）举办外展活动，以加强科学研究和提高公众的科学意识。建议的项目将探讨催化C-H键活化的基本问题。待开发的工具利用普遍存在的辅因子的同位素标记，因此将有助于在国内外的许多实验室中研究许多酶。测试的概念将影响化学和生物学，并可能影响合理的药物设计，仿生催化剂设计，以及在分子水平上对进化的理解。研究和教学活动将涉及广泛的机构，从K-12到研究型大学。在小学和中学阶段，这些活动将提高在高中选择科学选修课的学生（即潜在的未来科学家）的比例。他们还将鼓励可能选择非科学职业的学生（如未来的政策制定者和公众）对科学采取同情的观点，以及更好地理解科学在人类福祉中发挥的关键作用。与具有小型研究项目的学院的合作努力将扩大未来博士的范围。学生此外，这些项目旨在使不同群体的学生能够参与。为此，将继续努力从代表性不足的群体中招募、培训和教育学生。在过去的四年里，科恩博士有五个少数民族学生与他的小组一起工作。此外，科恩博士的小组中男女人数相等，学生来自不同的背景。该项目的研究结果、方法和想法将通过出版物和会议报告的方式传播，有用的计算机程序将免费张贴在网上，和实验数据将提供给任何有兴趣分析类似化学和生物系统的研究人员。该项目由生命过程化学联合支持化学系的生物分子动力学，结构和功能群，分子和细胞生物科学系。

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.