Investigation of Protein Dynamics on Multiple Timescales by Neutron Scattering and Molecular Dynamics Simulations

该项目将利用中子散射和分子动力学模拟研究深海热喷口群落中发现的超嗜热微生物的蛋白质。总体目标是发展蛋白质动力学和结构之间的关系的基本理解，并在分子水平上将这些信息与生物学功能相关联。将被研究的蛋白质具有在极端压力和温度下进行催化活性的能力。这样的研究将给出不同条件下蛋白质动力学和构象变化的完整图像。它将提供一个框架，全面和系统的研究动态的生物系统在不同的时间尺度。这个跨学科的项目涵盖了各个领域，包括物理化学，统计力学，结构生物学和计算生物化学。因此，参与该项目的学生将在多学科环境中接受培训。综合研究和教育推广将使学生接触到生物物理学的前沿研究。它将改善底特律市中心初中和高中的生物物理教学和教育，那里有大量未被代表的群体，几乎没有接触到现代科学技术。蛋白质的生物功能，如催化，通常从它们的晶体结构中理解;然而，为了充分理解这些功能，考虑动力学行为至关重要。蛋白质在空间和时间上经历复杂的变化，以保持细胞的功能。这些运动被认为在多个时间尺度上控制蛋白质的生物学功能和活动。中子散射是在分子水平上真实的时间内研究蛋白质结构和动力学的一种特殊工具。 本项目将开展补充中子散射实验和理论模拟，在分子水平上研究压力和温度对不同时间尺度上蛋白质动力学和结构变化的影响：（1）通过小角中子和X射线散射监测和分析结构变化;（2）将利用准弹性中子散射研究与生物活动最相关的ps至ns时间尺度的中期动力学;（3）在微秒到毫秒的长时间范围内，用中子自旋回波探测蛋白质结构域的运动;（4）短时间动力学，在小于ps的时间范围内，蛋白质中的类声子运动将通过非弹性中子和X射线散射来研究;（5）理论模型和分子动力学模拟将用于解释和扩展中子散射实验数据。

This project will utilize neutron scattering and molecular dynamics simulations to study proteins from hyperthermophilic microorganism found in deep-sea thermal vent communities. The overall objective is to develop a fundamental understanding of the relationship between protein dynamics and structures, and to correlate this information with biological functions at the molecular level. The proteins that will be studied have the ability to perform catalytic activity at extreme pressures and temperatures. Such a study will give a complete picture of protein dynamics and conformational changes under different conditions. It will provide a framework for comprehensive and systematic studies of the dynamics in biological systems under various timescales. This interdisciplinary project encompasses various fields, including physical chemistry, statistical mechanics, structural biology, and computational biochemistry. Therefore, students involved in this project will be trained in a multidisciplinary environment. The integrated research and educational outreach will expose students to cutting-edge research in biophysics. It will improve biophysics teaching and education in inner-city middle and high school in Detroit, where there is a large population of under-represented groups with little exposure to modern scientific techniques.The biological functions of proteins, such as catalysis, are often understood from their crystallographic structures; however, it is crucial to take into account dynamic behaviors in order to fully comprehend these functions. Proteins undergo sophisticated changes in space and time, in order to keep the cells functioning. These motions are believed to govern the biological function and activities of the protein on multiple time scales. Neutron scattering is an exceptional tool for studying the structures and dynamics of proteins in real time at the molecular level. In this project, complementary neutron scattering experiments and theoretical simulations will be carried out to study the effect of pressure and temperature on protein dynamics and structural changes on different timescales at the molecular level: (1) the structural changes will be monitored and analyzed by small angle neutron and X-ray scattering; (2) mid-time dynamics in ps to ns timescales, which is most relevant to biological activity, will be studied by quasi-elastic neutron scattering; (3) in the long-time range, from microsecond to millisecond, protein domain motions will be probed by neutron spin echo; (4) the short-time dynamics, in less than ps time range, phonon-like motions in proteins will be investigated by inelastic neutron and X-ray scattering; (5) theoretical modeling and molecular dynamics simulations will be employed to interpret and extend neutron scattering experimental data.