Computer Simulation Studies of the Thermodynamics and Kinetics of Protein Folding and Aggregation

蛋白质折叠和聚集的热力学和动力学的计算机模拟研究

• 批准号: 9704044
• 负责人: Carol Hall
• 金额: $ 20.05万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9704044&HistoricalAwards=false
• 关键词: Computer; Simulation; Studies; Thermodynamics; Kinetics

ABSTRACT CTS-9704044 Carol Hall/N.C. State This proposal describes a program of theoretical research aimed at understanding the mechanisms by which solutes such as polyethylene glycol (PEG) enhance the refolding of proteins and prevent aggregation. The goal is to develop molecular-level models that capture the essential features that govern the competition protein refolding and aggregation in both the presence and absence of solutes. By simulating the properties of model proteins and solutes on the computer, we will be able to explore how protein folding and kinetics are influenced by: protein type and concentration; denaturant type and concentration; solute type; concentration, and size; and temperature. The investigators will work on three parallel tracks whose objectives are: (1) to extend the two dimensional lattice Monte Carlo studies of protein folding and aggregation previously performed under NSF sponsorship to include the presence of model solutes that mimic the effect of PEG, (2) to develop simple off-lattice models based on the heteronuclear square-well chain model and then to use discontinuous molecular dynamic (DMD) to simulate protein folding and aggregation in the presence and absence of model PEG molecules. ***

摘要 CTS-9704044 卡罗尔·霍尔/北卡罗来纳州该提案描述了一项理论研究计划，旨在了解聚乙二醇 (PEG) 等溶质增强蛋白质重折叠并防止聚集的机制。目标是开发分子水平模型，捕获在存在和不存在溶质的情况下控制竞争蛋白重折叠和聚集的基本特征。 通过在计算机上模拟模型蛋白质和溶质的特性，我们将能够探索蛋白质折叠和动力学如何受到以下因素的影响：蛋白质类型和浓度；变性剂类型和浓度；溶质类型；浓度和大小；和温度。 研究人员将在三个平行的轨道上开展工作，其目标是：（1）扩展先前在 NSF 赞助下进行的蛋白质折叠和聚集的二维晶格蒙特卡罗研究，以包括模拟 PEG 效应的模型溶质的存在，（2）开发基于异核方井链模型的简单离格模型，然后使用不连续分子动力学（DMD）进行模拟 在存在和不存在模型 PEG 分子的情况下蛋白质折叠和聚集。 ***