Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA 92093.
Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 2018 May 8;115(19):4933-4938. doi: 10.1073/pnas.1719391115. Epub 2018 Apr 23.
High protein concentrations complicate modeling of polymer assembly kinetics by introducing structural complexity and a large variety of protein forms. We present a modeling approach that achieves orders of magnitude speed-up by replacing distributions of lengths and widths with their average counterparts and by introducing a hierarchical classification of species and reactions into sets. We have used this model to study FtsZ ring assembly in The model's prediction of key features of the ring formation, such as time to reach the steady state, total concentration of FtsZ species in the ring, total concentration of monomers, and average dimensions of filaments and bundles, are all in agreement with the experimentally observed values. Besides validating our model against the in vivo observations, this study fills some knowledge gaps by proposing a specific structure of the ring, describing the influence of the total concentration in short and long kinetics processes, determining some characteristic mechanisms in polymer assembly regulation, and providing insights about the role of ZapA proteins, critical components for both positioning and stability of the ring.
高浓度的蛋白质会使聚合物组装动力学的建模变得复杂，因为这会引入结构的复杂性和大量的蛋白质形式。我们提出了一种建模方法，通过用平均值代替长度和宽度的分布，并将物种和反应的层次分类引入到集合中，从而实现了数量级的加速。我们已经使用该模型研究了 FtsZ 环的组装。
该模型对环形成的关键特征的预测，如达到稳定状态的时间、环中 FtsZ 物种的总浓度、单体的总浓度以及纤维和束的平均尺寸，都与实验观察到的值一致。除了将我们的模型与体内观察结果进行验证外，这项研究还通过提出环的特定结构、描述在短时间和长时间动力学过程中总浓度的影响、确定聚合物组装调节中的一些特征机制，以及提供有关 ZapA 蛋白的作用的见解，为填补知识空白做出了贡献。ZapA 蛋白是环的定位和稳定性的关键组成部分。
