LOCAL AND LONG RANGE INTERACTIONS IN PROTEIN FOLDING

描述：关于蛋白质折叠和稳定性的完整描述如下 现代生物化学中最重要的问题之一。要充分实现 肖尔茨博士不断增长的基因组信息知识的潜力，他必须 了解蛋白质折叠的规则。这项建议 阐述了蛋白质稳定性和折叠范围方面的一些非常基本的问题 从静电相互作用在定义折叠和展开中的作用 蛋白质的构象对网络之间相互作用的作用 极性残基对蛋白质折叠速度、最终稳定性的影响 褶皱构造及其褶皱机制。肖尔茨博士的基本方法是 在不同的蛋白质或变种之间进行定量比较 更改特定属性。这些比较涵盖了全球结构和 对相互作用的详细原子能级描述的稳定性测量 折叠反应的动力学研究。一个完整的分子和定量 蛋白质折叠规则的描述只能通过以下方式实现 像这里介绍的那些研究。 该提案涉及蛋白质折叠和稳定性方面的两个主要主题：1) 静电相互作用在确定结构和结构中的作用是什么 蛋白质折叠和未折叠构象的稳定性，以及2)如何 极性基团之间相互作用的复杂网络支配着稳定性和 球状蛋白质的折叠？肖尔茨博士将使用各种不同的 探索蛋白质分子作用力的实验技术 稳定性、折叠性和结构。该程序的优势在于使用了 比较-蛋白质的单部位变体之间的比较， 蛋白质和模型肽之间的关系以及蛋白质在 不同的溶解条件。这种基础广泛的比较方法将允许 等电点为了更好地理解蛋白质折叠的规则， 稳定性和结构，这些规则将有助于回答这些非常基本的问题 分子医学中的问题。

DESCRIPTION: A complete description of protein folding and stability remains as one of the most important questions in modern biochemistry. To realize the full potential of Dr. Scholtz's growing knowledge of genome information, he must come to an understanding of the rules for protein folding. This proposal addresses some very fundamental issues in protein stability and folding ranging from the role of electrostatic interactions in defining the folded and unfolded conformations of proteins to the role that interactions between networks of polar residues have on the rate of protein folding, the stability of the final folded structure and the mechanism of folding. Dr. Scholtz's basic approach is to make quantitative comparisons between different proteins or variants that alter a specific property. These comparisons encompass global structural and stability measurements to detailed atomic level descriptions of interactions to kinetic studies on the folding reactions. A complete molecular and quantitative description of the rules for protein folding will only be achieved through studies such as those presented here. This proposal addresses two major topics in protein folding and stability: 1) What are the roles of electrostatic interactions in defining the structure and stability of the folded and unfolded conformations of a protein, and 2) How do complex networks of interactions between polar groups govern the stability and folding of globular proteins? Dr. Scholtz will use a variety of different experimental techniques to explore the molecular forces responsible for protein stability, folding and structure. The strength of the program is the use of comparisons-comparisons between single-site variants of proteins, between proteins and model peptides and between the properties of a protein under different solution conditions. This broad-based comparative approach will allow the PI to reach a better understanding of the rules for protein folding, stability and structure and these rules will help answer these very basic questions in molecular medicine.