Effects of macromolecular crowding on protein structure, folding, and interactions

蛋白质折叠是一个重要的生物学过程，因为蛋白质需要折叠成独特的结构以在细胞中发挥适当的功能。由于细胞内复杂的相互作用的干扰，在活体标本上进行实验是困难的。该项目的目的是研究拥挤剂存在下蛋白质折叠的统计和动力学特性，使用实验和计算相结合的方法。 对这种在空间和时间尺度上覆盖几个数量级的复杂系统的研究需要粗粒度分子模拟和细粒度原子模拟的技术。这些方法将被战略性地整合到一个多尺度的方法中，从而能够在现实条件下研究蛋白质动力学。从研究中获得的知识将用于发现体内蛋白质折叠的物理原理，并预测只能在细胞内部看到的新现象。 一个集成的多尺度建模和仿真方法将被应用于提高复杂的蛋白质动力学在生命系统中的知识。该项目将促进与瑞典Pernilla Wittung-Stafshede博士实验小组的国际研究合作，该项目将通过在休斯顿大学（美国种族最多元化的研究型大学之一）进行物理学、化学和生物学跨学科领域的实践研究，对本科生和研究生进行培训。学生将学习高性能计算的范例，分子模拟算法和物理原理，以更好地了解分子水平上的生物系统。新开发的多尺度建模和模拟软件将通过互联网提供给科学界。PI计划在她对休斯顿地区高中的定期访问中使用该软件，并继续鼓励妇女和代表性不足的群体从事科学和工程职业。PI还计划为本科生和高中教师举办暑期教育研讨会，为参与者提供将该软件应用于生物物理学研究的实践经验，作为影响科学教育的有效教学方法。

Protein folding is an important biological process because proteins are required to fold into unique structures for proper functionality in cells. Experiments on living specimens are difficult to perform because of the interference from complex interactions in a cell. The aim of this project is to investigate statistical and kinetic properties of protein folding in the presence of crowding agents using a combined experimental and computational approach. Studies of such complex systems covering several orders of magnitude in spatial and temporal scales require techniques from coarse-grained molecular simulation and fine-grained atomistic simulations. These methods will be strategically integrated into a multi-scale approach which enables the investigation of protein dynamics in realistic conditions. The knowledge obtained from the research will be used to discover physical principles of protein folding in vivo and predict new phenomena that can only be seen in the interior of a cell. An integrated multi-scale modeling and simulation approach will be applied to enhance knowledge of complex protein dynamics in living systems. The project will advance international research collaboration with the experimental group of Dr. Pernilla Wittung-Stafshede in Sweden.This project will involve training of undergraduate and graduate students through hands-on research in the interdisciplinary fields of physics, chemistry and biology at the University of Houston, one of the most ethnically diverse research universities in the country. Students will learn about paradigms for high-performance computing, algorithms for molecular simulations, and physical principles to better understand biological systems at a molecular level. Newly developed multiscale modeling and simulation software will be made available to the scientific community through the internet. The PI plans to include the use of this software in her regular visits to high schools in the Houston area and to continue encouragement of women and underrepresented groups to pursue careers in sciences and engineering. The PI also plans to host summer educational workshops for undergraduate students and high school teachers that will provide participants with hands-on experience in applying this software to biophysics research as an effective teaching and learning approach to impact science education.