RUI: Probing the Free Energy Landscape of Protein Hydrophobic Cores by Solid-State NMR

在过去的二十年里，人们已经清楚地认识到蛋白质的形状和结构不是静态的-这些分子“呼吸”，它们的结构波动。这些运动不仅本身有趣，而且对蛋白质的许多功能也很重要。该项目的重点是疏水核心，这是蛋白质的一部分，隐藏在远离水的地方。为了获得核心内部运动的详细图像，选定的氢原子将被改变为氘核，它们具有相同的化学性质，但具有不同的磁性。然后将使用核磁共振光谱法来跟踪选定部位的运动。这项研究将探索蛋白质分子周围的运动对温度和水量的依赖性，以揭示势能的特征。通过对蛋白质核心区域波动的定量研究，本项目将有助于阐明蛋白质动力学的物理因素。本项目的更广泛的目的是让阿拉斯加大学安克雷奇分校的本科生接触到安克雷奇地区无法获得的最先进的仪器。这项工作的跨学科性质，跨越化学，生物学，物理学，数学和计算机科学，允许欣赏多种方法来解决当代科学问题，以及将来自不同学科的学生纳入该项目。阿拉斯加大学有很大比例的学生来自代表性不足的群体，如阿拉斯加原住民，并将作出特别努力，通过与阿拉斯加土著科学和工程计划已经建立的联系，以吸引这批学生。

During the last two decades it has become clear that the shapes and structures of proteins are not static - these molecules "breathe" and their structures fluctuate. These motions are not only interesting by themselves, but also important for the many functions of proteins. This project focuses on the hydrophobic core, which is the part of the protein that is hidden away from water. To get a detailed picture of motions inside the core, selected hydrogen atoms will be changed to deuterons, which have identical chemical properties but different magnetic ones. Nuclear magnetic resonance spectroscopy will then be used to follow the motions at the selected sites. The investigation will probe the dependence of the motions on temperature and amount of water around the protein molecule to reveal the characteristics of the potential energy. By focusing on quantitative investigations of fluctuations in the core region of proteins, this project will contribute toward elucidation of physical factors that govern protein dynamics.This project has the broader purpose of exposing undergraduate students at the University of Alaska at Anchorage, which is a predominantly undergraduate institution, to state-of-the-art instrumentation that is not available to them in the Anchorage area. The interdisciplinary nature of the work, spanning chemistry, biology, physics, mathematics, and computer science, allows for the appreciation of multiple approaches to solving contemporary scientific problems, as well as for the incorporation of students from various disciplines into the project The University of Alaska has a large percentage of students from underrepresented groups, such as Alaska Natives, and special effort will be made to attract this group of students through an already established connection with the Alaska Native Science and Engineering Program.