Thermodynamics of Protein Unfolding/Refolding

这项建议的目标遵循两个平行的发展， 热力学在蛋白质问题上的应用 展开 一个是解决与以下方面有关的基本问题： 溶剂诱导和热解折叠热力学 蛋白质和其他涉及使用热力学 氧化还原态去折叠的研究技术 硫氧还蛋白和突变硫氧还蛋白种类。 硫氧还蛋白是一种 其中蛋白质稳定性的变化是一个整体的蛋白质 它的功能方面。 热力学研究的展开 硫氧还蛋白和该蛋白的位点特异性突变形式可以 用于建立基本规则和约束， 硫氧还蛋白折叠的机制研究必须符合。 从历史上看，有两种主要的方法来解决这个问题 蛋白质折叠的过程。 其中一个，主要是强调热力学， 关注蛋白质种类的稳定性，并试图 了解导致本地稳定的力量 （折叠）状态。 另一种方法，使用动力学研究 在很大程度上，侧重于折叠的机制， 理解最终导致 折叠的天然蛋白质。 这两种方法都有 有助于我们今天对蛋白质折叠的理解。

The goals of this proposal follow two parallel developments in the application of thermodynamics to problems of protein unfolding. One addresses fundamental issues associated with thermodynamics of solvent-induced and thermal unfolding of proteins and the other involves the use of thermodynamic techniques in studies of the unfolding of oxidized and reduced thioredoxin and mutant thioredoxin species. Thioredoxin is a protein in which a change in protein stability is an integral aspect of it function. Thermodynamic studies of the unfolding of thioredoxin and site-specific mutant forms of this protein can be used to establish the ground rules and constraints to which mechanistic studies of thioredoxin folding must conform. Historically, there have been two major approaches to the problem of protein folding. One, largely thermodynamic in emphasis, is concerned with the stability of protein species and attempts to understand the forces which lead to stabilization of the native (folded) state. The other approach, which uses kinetic studies to a large extent, focuses on mechanisms of folding with the goal of understanding the molecular events which ultimately lead to the folding native protein. Both of these approaches have contributed to the present day understanding of protein folding.