STRUCTURAL/THERMODYMANIC STUDIES OF FOLDING AND BINDING

蛋白质折叠、蛋白质相互作用和蛋白质-蛋白质相互作用的过程， 肽结合是生物系统中许多现象的基础。 对这些过程的理解发展到一个水平， 在产生关于自由能的准确预测方面很有用 与这些进程有关的问题将具有深远的重要性。 的 这种知识的产生需要并行的高分辨率结构 研究和高分辨率的热力学研究。 结构研究 详细揭示了在过程中相互作用的表面和群体， 这些过程，而热力学研究表明， 熵对自由能的贡献是温度的函数。 这两类数据的比较和相互关系是必要的， 产生形成基于结构的基础的所需信息 热力学分析 模型已经并正在开发，可以 适用于适当的系统。 这些模型包括一些术语， 与基本原则和其他 基于经验实验数据进行参数化。 这些模型将 通过对一系列重要系统的研究， 包括金属结合蛋白，肽结合抗体，肌动蛋白， 结合蛋白、肽结合抗体、肌动蛋白结合蛋白和 它们的复合物，肽-肽相互作用，蛋白酶抑制剂 相互作用，以及多肽和蛋白质未折叠状态的模型。 将利用的技术包括X射线晶体学、核分析、X射线晶体学和X射线晶体学。 磁共振光谱、滴定和差示扫描 量热法和计算方法。

The processes of protein folding, protein-protein interaction, and protein- peptide binding are fundamental to many phenomena in biological systems. The development of an understanding of these processes at a level that is useful in terms of generating accurate predictions about the free energies associated with such processes would be of profound importance. The generation of this knowledge requires parallel high resolution structural studies and highly resolved thermodynamic studies. The structural studies reveal in detail the surfaces and groups that interact in the course of these processes whereas the thermodynamic studies reveal the enthalpic and entropic contributions to the free energy as a function of temperature. The comparison and correlation of these two types of data is necessary to yield the desired information that form the basis of structure based thermodynamic analysis. Models have been and are being developed that can be applied to appropriate systems. These models include some terms that are closely linked to fundamental principles and others that are parameterized based on empirical experimental data. Such models will be tested, refined, and extended through studies of a set of important systems that include metal-binding proteins, peptide-binding antibodies, actin- binding proteins, peptide-binding antibodies, actin-binding proteins and their complexes, peptide-peptide interactions, protease-inhibitor interactions, and models for the unfolded states of peptides and proteins. The techniques to be utilized include X-ray crystallography, nuclear magnetic resonance spectroscopy, titration and differential scanning calorimetry, and computational methods.