Fast Conformational Relaxation in Model Peptides

模型肽中的快速构象松弛

• 批准号: 6706162
• 负责人: WILLIAM DEGRADO
• 金额: $ 6.87万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6706162
• 关键词: chemical models; cofactor; conformation; crosslink; disulfide bond; electronic spectra; heme; infrared spectrometry; interferometry; molecular dynamics; peptide chemical synthesis; peptide structure; porphyrins; protein folding; protein protein interaction; protein structure function; reducing agents; synthetic peptide; thermostability; time resolved data; chemical models; cofactor; conformation; crosslink; disulfide bond; electronic spectra; heme; infrared spectrometry; interferometry; molecular dynamics; peptide chemical synthesis; peptide structure; porphyrins; protein folding; protein protein interaction; protein structure function; reducing agents; synthetic peptide; thermostability; time resolved data

We seek to understand protein and cofactor conformational and chemical dynamics through the design and synthesis of peptides and small proteins. This work should provide a fundamental framework for understanding a variety of kinetic phenomena ranging from the folding and misfolding of proteins to the structural and dynamic bases for the function of redox enzymes. As a part of a program project, we strive to develop synthetic and computational methods that can be use across the entire program, and we also apply these methods to study protein hydration, folding, and design. In particular, our aims are as follows: 1) We will develop temperature-dependent isotope-edited IR spectroscopy as a method to monitor conformational change, and apply it to determine the nanosecond to microsecond events in protein folding. 2) We will synthesize nitrile-containing amino acids and examine their utility as environment-sensitive probes of protein-protein interactions, protein folding, and protein membrane interactions. 3) We will design proteins that bind a variety of hemes, porphyrins, and other synthetic cofactors, and determine the functional properties and structures of these proteins.

我们试图通过设计和合成肽和小蛋白质来理解蛋白质和辅因子构象和化学动力学。这项工作应提供一个基本的框架，以理解从蛋白质的折叠和折叠到氧化还原酶功能的结构和动态碱的各种动力学现象。作为计划项目的一部分，我们努力开发可以在整个程序中使用的合成和计算方法，并且还将这些方法应用于研究蛋白质水合，折叠和设计。特别是，我们的目标如下：1）我们将开发依赖温度的同位素编辑的红外光谱法作为监测构象的方法 更改，并将其应用于蛋白质折叠中的微秒事件的纳秒。 2）我们将合成含氮的氨基酸，并将其用作蛋白质蛋白相互作用，蛋白质折叠和蛋白质膜相互作用的环境敏感探针进行研究。 3）我们将设计结合各种血液，卟啉和其他合成辅助因子的蛋白质，并确定这些蛋白质的功能特性和结构。