A Molecular Study of Min-Protein Polymer Dynamics

描述（由申请人提供）：在大肠杆菌和相关细菌中，细胞分裂的显著准确性部分受到Minprotein系统的调节，该系统通过从极点到极点的空间振荡来阻止细胞末端附近的分裂。这位科学家最近开发了一个完整的Min系统模型，只使用已知的蛋白质特性，准确地再现了观察到的振荡，并预测了MinD蛋白质的有限核苷酸交换率，大约为一秒，这个数字已经被实验验证为高度精确。这项提议涉及在杆状细胞中发展颗粒级模拟的努力，以首次捕获Min蛋白的螺旋聚合物动力学。此外，科学家打算将模型扩展到圆形细胞，以确定Min振荡是否可以在存在统计波动的情况下自发选择细胞的长轴来定义球菌的分裂平面。这些粒子级模拟为了解原核生物和真核生物如何使用反应扩散蛋白质系统将蛋白质靶向到不同位置并检测其自身的几何形状提供了一个起点，并将在大规模计算和蛋白质相互作用的微尺度生物学之间的扩展界面上具有广泛的应用。为了了解大肠杆菌令人难以置信的分裂精度背后的机制，科学家将进行结合计算结果的实验，研究浓度变化对振荡周期和分裂精度的影响。理论工作将在普林斯顿大学Ned Wingreen博士的实验室进行，实验资源和培训由普林斯顿大学Bonnie Bassler博士提供。

DESCRIPTION (provided by applicant): The remarkable accuracy of cell division in E. coli and related bacteria is partially regulated by the Minprotein system, which prevents division near the cell ends by oscillating spatially from pole to pole. The scientist has recently developed a complete model of the Min system, using only known properties of the proteins, which accurately reproduces the observed oscillations and predicts a finite nucleotide exchange rate for the MinD protein of around one second, a number that has since been experimentally verified to a high degree of accuracy. This proposal concerns efforts to develop particle-level simulations in rod-shaped cells, to capture for the first time the helical polymer dynamics of the Min proteins. In addition, the scientist intends to extend the model to round cells, to determine whether Min oscillations can spontaneously select the long axis of the cell to define the division plane in cocci in the presence of statistical fluctuations. These particle-level simulations provides a starting point for a general understanding of how prokaryotes and eukaryotes can use a reaction-diffusion protein system to target proteins to different locations and to detect their own geometry, and will have broad applications at the expanding interface between large-scale computation and the microscale biology of protein interactions. In order to understand the mechanism behind E. coli's incredible division accuracy, the scientist will undertake experiments incorporating computational results to study the effects of changes in concentration on oscillation period and division accuracy. The theoretical work will be performed in Dr. Ned Wingreen's lab at Princeton University, with experimental resources and training provided by Dr. Bonnie Bassler at Princeton University.