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

有了这个奖项，化学部的生命过程化学计划正在资助科罗拉多丹佛大学的Elan Eisenmesser博士研究酶内的运动如何交流以控制酶的功能。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，依赖于一系列运动来实现其功能。然而，这些运动是如何通过酶来控制它们的功能的，人们还不太了解。 利用新开发的技术，桥梁分子生物学和核磁共振，研究生和本科生将揭示如何在多个时间尺度上的运动在一个关键的生物酶，称为胆红素还原酶B内通信，以及是否有不同的时间尺度上的运动之间的串扰。这些研究可能会影响工程酶的努力，同时考虑它们的结构和内在运动。Eisenmesser博士还计划将这些研究介绍给少数民族大学生，以培养学生掌握分子生物学和最先进的生物物理技术，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，以及这些网络如何反过来调节催化转换。 动态通信现在被很好地理解为在酶功能中起关键作用，并且许多最近的研究表明，运动仅部分相关。 因此，确定这些部分耦合的分子基础，并专门调节远端动力学，以控制酶的功能将显着影响酶engineering.This奖项反映了NSF的法定使命的努力，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.