STRUCTURAL/THERMODYMANIC STUDIES OF FOLDING AND BINDING

蛋白质折叠、蛋白质-蛋白质相互作用和蛋白质- 多肽结合是生物系统中许多现象的基础。 在一定程度上发展对这些过程的理解 在生成关于自由能的准确预测方面很有用 与这类进程相关的问题将具有极其重要的意义。这个 这种知识的生成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 详细揭示在过程中相互作用的表面和群 这些过程，而热力学研究揭示了热焓和 作为温度函数的自由能的熵贡献。 有必要对这两种类型的数据进行比较和关联 产生所需的信息，形成基于结构的 热力学分析。已经和正在开发的模型可以 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本原则密切相关 基于经验实验数据的参数化。这样的模式将是 通过对一组重要系统的研究来测试、提炼和扩展 包括金属结合蛋白、多肽结合抗体、肌动蛋白- 结合蛋白、多肽结合抗体、肌动蛋白结合蛋白和 它们的络合物、肽-肽相互作用、蛋白酶抑制物 相互作用，以及多肽和蛋白质的展开状态的模型。 将使用的技术包括X射线结晶学、原子核 磁共振波谱、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.