Determining the role of dynamics in allosteric communication and function for BLVRB

有了这个奖项，化学部门的生命过程化学项目资助了科罗拉多大学丹佛分校的Elan Eisenmesser博士，研究酶内部的运动是如何沟通来控制酶的功能的。在过去的二十年里，随着能够识别分子中所有原子位置的技术方法的发展，人们越来越清楚地认识到，大分子，特别是酶，依赖于一系列的运动来实现它们的功能。然而，这些运动是如何通过一种酶来沟通以控制它们的功能的，人们还不太了解。利用分子生物学和核磁共振的新开发技术，研究生和本科生将揭示在多个时间尺度上的运动是如何在一种叫做胆红素还原酶B的关键生物酶中进行交流的，以及不同时间尺度上的运动之间是否存在串音。这些研究可能会影响通过考虑酶的结构和内在运动来设计酶的努力。Eisenmesser博士还计划将这些研究介绍给少数民族本科生，以培养学生在分子生物学和最先进的生物物理技术方面的能力，这些技术可以探测结构和运动的原子水平细节。该研究项目旨在阐明耦合运动网络如何调节活性位点动力学以及这些运动反过来如何调节催化周转。动态交流在酶的功能中起着至关重要的作用，最近的许多研究表明，运动只是部分相关的。因此，确定这些部分偶联的分子基础和特异性调节远端动力学以控制酶功能将对酶工程的努力产生重大影响。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Elan Eisenmesser from the University of Colorado Denver to investigate how motions within an enzyme communicate to control enzyme function. With the development of technological methods capable of identifying the positions of all the atoms in molecules over the last two decades, it has become increasingly clear that macromolecules, and particularly enzymes, are reliant on a range of motions for their functions. However, how these motions are communicated across an enzyme in order to control their functions is less understood. Utilizing newly developed techniques that bridge molecular biology and nuclear magnetic resonance, graduate and undergraduate students will reveal how motions on multiple timescales communicate within a critical biological enzyme, called Bilirubin Reductase B, and whether there is cross-talk between movements on different timescales. Such studies could impact efforts to engineer enzymes by considering both their structure and intrinsic motions. Dr. Eisenmesser also plans to introduce these studies to minority undergraduates in order to train students in molecular biology and state-of-the-art biophysical techniques that probe the atomic level details of both structure and motions.The research project is aimed at elucidating how networks of coupled motions regulate active site dynamics and how these in turn modulate catalytic turnover. Dynamic communication is now well understood to play critical roles in enzyme function and many recent studies have shown that motions are only partially correlated. Thus, identifying the molecular basis of these partial couplings and specifically modulating distal dynamics in order to control enzyme function will significantly impact efforts for enzyme engineering.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.