Topics in Protein Folding and Protein Dynamics

Dev Thirumalai得到了化学部理论和计算化学项目以及分子和细胞生物科学部分子生物物理学项目的资助，以继续开展蛋白质折叠和蛋白质动力学方面的工作。这项工作的特点是发展了解释各种主题的算法和理论，例如力诱导蛋白质的去折叠和β-发夹结构的组装。这些概念和方法被用来做出可以在实验中检验的精确预测。目前的项目集中在三个方面：1)更好地了解蛋白质折叠的基本过程，如环形成和β-发夹形成；2)研究尿素诱导变性的机制；3)研究伴侣辅助的蛋白质折叠。这项工作的大部分依赖于统计力学和用于玻璃研究的模拟。在这个项目中，Thirumalai的理论和计算研究与最近的实验工作之间有着密切的联系，而这种联系在类似的计算研究中往往是缺失的。这里使用的理论方法将提供对蛋白质折叠性质的基本理解，例如为什么特定的氨基酸序列采用特定的折叠构象。这些问题目前处于蛋白质研究的前沿，对影响蛋白质折叠的因素的基本了解可能会对生物技术行业产生巨大影响。

Dev Thirumalai is supported by a grant from the Theoretical and Computational Chemistry Program in the Chemistry Division and the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences to continue work on protein folding and protein dynamics. This work is characterized by the development of algorithms and theories to interpret various topics, such as the force-induced unfolding of proteins and the assembly of beta-hairpin structures. These concepts and methods are used to make precise predictions that can be tested in experiments. This current project focuses on three areas: 1) obtaining a greater understanding of elementary processes in protein folding, such as loop formation and beta-hairpin formation; 2) investigating the mechanism of urea-induced denaturation; and 3) studying the chaperone-assisted folding of proteins. Much of this work relies on statistical mechanics and simulations that have been used for the studies of glasses.In this project there is a close connection between Thirumalai's theoretical and computational studies and recent experimental work, a connection that is often missing in similar computational investigations. The theoretical approach used here will provide a basic understanding of the folding properties of proteins, such as why a particular amino acid sequence adopts a particular folded conformation. Such problems are currently at the frontier of protein research, and a basic understanding of the factors that influence protein folding could have an enormous impact on the biotechnology industry.