Developing a spectroscopic toolkit for probing protein structure and folding

开发用于探测蛋白质结构和折叠的光谱工具包

基本信息

批准号：
8757830
负责人：
Carlos Raul Baiz
金额：
$ 3.07万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-15 至 2015-02-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8757830
关键词：
Address Alzheimer&apos s Disease Amides Biological Models Biological Process Biophysics Cereals DNA Sequence Rearrangement Data Development Drug Interactions Environment Event Free Energy Frequencies Genetic Goals Heterogeneity Huntington Disease Hydrogen Bonding Kinetics Lasers Lead Link Maps Measures Methods Modeling Molecular Molecular Structure Motion Neurodegenerative Disorders Parkinson Disease Pathway interactions Process Protein Denaturation Proteins Resolution Sampling Side Simulate Solutions Solvents Spectrum Analysis Speed Stretching Structure Techniques Theoretical Studies Thermodynamics Time Vertebral column aggregation pathway base cluster computing flexibility globular protein infrared spectroscopy millisecond molecular dynamics nanosecond network models protein aggregation protein folding protein structure public health relevance research study response simulation temperature jump tool two-dimensional vibration

项目摘要

DESCRIPTION (provided by applicant): Understanding protein folding from a molecular perspective is one of the central challenges in modern biophysics. Current experimental techniques only provide a relatively limited view of the ultrafast fluctuations and long-range conformational changes that biomolecules undergo in solution. The first objective of this project is to develop an experimental framework based on ultrafast multidimensional infrared spectroscopy that will measure protein structure with sub- picosecond time resolution, offering a detailed view of non-equilibrium processes such as folding, denaturation, and protein aggregation. The experimental data will be supported by cutting-edge molecular dynamics simulations, which are now possible due to recent developments in distributed computing, as well as structure-frequency maps that provide the connection between molecular structures and vibrational frequencies. Another component of the project will aim at developing a general experimental method to quantify the structure of proteins in solution from an analytical perspective with the goal of implementing methods for measuring the structure, conformational flexibility, and solvent exposure of globular proteins.

描述（由申请人提供）：从分子角度了解蛋白质折叠是现代生物物理学的核心挑战之一。当前的实验技术仅提供了相对有限的观点，即在溶液中生物分子发生的超快波动和远程构象变化。该项目的第一个目标是基于超高多维红外光谱法开发实验框架，该光谱将通过亚比索分辨率分辨率进行测量蛋白质结构，从而详细介绍了非平衡过程，例如折叠，变性，变性和蛋白质聚集。实验数据将由尖端的分子动力学模拟支持，现在由于分布式计算中的最新发展以及结构频率图，这些模拟现在是可能的。该项目的另一个组成部分将旨在从分析的角度开发一种通用的实验方法，以实现测量结构，构象柔韧性和球状蛋白的溶剂暴露的方法来量化溶液中蛋白质的结构。