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

Carol Hall/N.C.该提案描述了一个旨在理解溶质（如聚乙二醇）增强蛋白质再折叠和防止聚集的机制的理论研究项目。目标是建立分子水平的模型，捕捉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性质，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。调查人员将在三个平行的轨道上工作，其目标是：(1)扩展以前在NSF赞助下进行的二维晶格蒙特卡罗蛋白质折叠和聚集研究，包括模拟PEG效应的模型溶质的存在；(2)基于异核方孔链模型开发简单的非晶格模型，然后使用不连续分子动力学（DMD）模拟模型PEG分子存在和不存在时的蛋白质折叠和聚集。＊＊＊

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. ***