CORE--CORE FACILITY

核心--核心设施

• 批准号: 6316672
• 负责人: Jeremy M. Berg
• 金额: $ 18.31万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-06-01 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6316672
• 关键词: X ray crystallography; bioimaging /biomedical imaging; biomedical facility; computer center; computer graphics /printing; computer simulation; high performance liquid chromatography; nucleic acid chemical synthesis; oligonucleotides; peptide chemical synthesis; protein protein interaction; protein purification; synthetic nucleotide; synthetic peptide

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 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 other 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 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.

蛋白质折叠、蛋白质-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定程度 对于生成有关自由能的准确预测很有用 与此类进程相关的研究将具有深远的重要性。 这 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揭示了焓和 熵对自由能的贡献作为温度的函数。 需要对这两类​​数据进行比较和关联 产生形成基于结构的基础的所需信息 热力学分析。 已经并正在开发的模型可以 应用于适当的系统。 这些模型包括一些术语 与基本原则和其他原则密切相关 根据经验实验数据进行参数化。 此类模型将是 通过对一组重要系统的研究进行测试、完善和扩展 包括金属结合蛋白、肽结合抗体、肌动蛋白 结合蛋白及其复合物、肽-肽相互作用、 蛋白酶-抑制剂相互作用，以及未折叠状态的模型 肽和蛋白质。 要利用的技术包括 X 射线 晶体学、核磁共振波谱、 滴定和差示扫描量热法，以及 计算方法。