Molecular Simulations of Folding & Association in Physiological Environments

结构生物学和定量蛋白质组学领域的最新进展意味着， 现在有足够的信息可以构建有意义的工作分子， 生理环境的模型。这种环境模型，当与模拟相结合时， 能够模拟系统动态的方法，将允许关键的生物化学 例如蛋白质折叠和蛋白质-蛋白质缔合事件等过程 更接近于在真实的生活中遇到的那些。这里提出的项目有两个 主要目标将并行追求：（1）分子模拟方法， 已经在PI实验室开发了几年的项目将被延长， 加速，使它们适合用于模拟非常大规模的动态 大分子系统（例如包含10，000个大分子），（2）结构生物学和 定量蛋白质组学数据将用于建立四个不同的初步3D模型， 在模式原核生物大肠杆菌的环境：细胞质，周质，和内部和 外膜

Recent advances in the field of structural biology and quantitative proteomics mean that there is now sufficient information available to allow the construction of meaningful, working molecular models of physiological environments. Such environmental models, when coupled to simulation methods that enable the dynamics of the systems to be modeled, will allow key biochemical processes such as protein folding and protein-protein association events to be observed in settings that much more closely mimic those encountered in real life. The project proposed here has two major objectives which will be pursued in parallel: (1) molecular simulation methods that have been under development in the PI's laboratory for some years will be extended and accelerated to make them suitable for use in simulating the dynamics of very large-scale macromolecular systems (e.g. comprising 10,000 macromolecules), (2) structural biological and quantitative proteomics data will be utilized to build preliminary 3D models of four different environments in the model prokaryote Escherichia coli: the cytoplasm, periplasm, and inner and outer-membranes