NSF Minority Postdoctoral Fellowship for FY 2009

这一行动为2009财年国家科学基金会少数民族博士后研究奖学金提供资金，并根据2009年《美国复苏和再投资法案》(公法111-5)提供资金。该奖学金支持在东道主实验室为该研究员制定的研究和培训计划，该研究员还提出了扩大生物学参与度的计划。卢卡斯·尼冯的这项研究和培训计划的标题是“新型酶的计算设计：催化双分子反应中碳-碳键的形成”。这项研究是在大卫·贝克博士的赞助下在华盛顿大学进行的。酶在生物体中负责各种各样的代谢功能，但天然酶不能催化大多数商业上重要的合成反应。这项研究通过使用化学原理为非自然反应设计新的酶来测试目前对酶功能的理解。通过使用新的算法来搜索合适的活性中心并设计原子精确的口袋来结合特定化学反应的过渡态，已经成功地生产出用于逆转-羟醛(RA)加成和Kemp消除的新型酶。这些反应是单分子的。这个项目正在通过研究与RA(Michael加成和前向Aldol加成)密切相关的两个反应来处理双分子、键形成反应，方法是重新设计这些双分子反应的RA酶。此外，正在研究的是Morita-Bayliss-Hillman(MBH)反应，该反应在现代合成中得到广泛应用，但在自然界中并不存在，目的是询问酶是否可以催化以前只有合成化学才知道的反应。培训计划包括学习蛋白质设计的计算方法，以及执行广泛的酶分析和大规模酶纯化所需的生化技能。通过使用已建立的酶功能理论来设计新的蛋白质，该项目将对这些理论进行批判性测试，并可能揭示酶功能的新基本原理。除了纯粹的生物化学，这项工作对生物技术和医学也很有用，允许设计用于工业应用或用作酶药物或诊断的新酶。更广泛的影响还包括对学生的教育宣传，特别是来自代表性不足群体的教育。

This action funds an NSF Minority Postdoctoral Research Fellowship for FY 2009 and is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). The fellowship supports a research and training plan in a host laboratory for the Fellow who also presents a plan to broaden participation in biology. The title of the research and training plan for this fellowship to Lucas Nivon is "Computational design of new enzymes: catalyzing carbon-carbon bond formation in bi-molecular reactions." This research is being conducted at The University of Washington under the sponsorship of Dr. David Baker. Enzymes are responsible for the wide variety of metabolic functions in living organisms but natural enzymes cannot catalyze most commercially important synthetic reactions. This research tests current understanding of enzyme function by using chemical principles to computationally design new enzymes for non-natural reactions. Novel enzymes have been successfully produced for a retro-Aldol (RA) addition and the Kemp elimination by using new algorithms to search for appropriate active sites and to design atomically-accurate pockets to bind the transition states of particular chemical reactions. These reactions are uni-molecular. This project is tackling bimolecular, bond-forming reactions by studying 2 reactions closely related to the RA (Michael addition and forward Aldol addition) by re-designing RA enzymes for these bimolecular reactions. Additionally under study is the Morita-Bayliss-Hillman (MBH) reaction, which is widely applied in modern syntheses, but is nonexistent in nature, to ask whether enzymes can catalyze a reaction previously known only to synthetic chemistry.Training plans include learning computational methods of protein design and the biochemical skills necessary to perform a wide range of enzymatic assays and large-scale enzyme purifications. By using established theories of enzyme function to design new proteins this project will critically test those theories and perhaps reveal new basic principles of enzyme function. Outside of pure biochemistry this work is useful for biotechnology and medicine, allowing the design of new enzymes for industrial applications or for use as enzyme drugs or diagnostics. Broader impacts also include educational outreach to students, especially from under-represented groups.