Pan Weichun, Kolomeisky Anatoly B, Vekilov Peter G
Department of Chemical Engineering, University of Houston, TX 77204-4004, USA.
J Chem Phys. 2005 May 1;122(17):174905. doi: 10.1063/1.1887168.
Nucleation of ordered solid phases of proteins triggers numerous phenomena in laboratory, industry, and in healthy and sick organisms. Recent simulations and experiments with protein crystals suggest that the formation of an ordered crystalline nucleus is preceded by a disordered high-density cluster, akin to a droplet of high-density liquid that has been observed with some proteins; this mechanism allowed a qualitative explanation of recorded complex nucleation kinetics curves. Here, we present a simple phenomenological theory that takes into account intermediate high-density metastable states in the nucleation process. Nucleation rate data at varying temperature and protein concentration are reproduced with high fidelity using literature values of the thermodynamic and kinetic parameters of the system. Our calculations show that the growth rate of the near-critical and supercritical ordered clusters within the dense intermediate is a major factor for the overall nucleation rate. This highlights the role of viscosity within the dense intermediate for the formation of the ordered nucleus. The model provides an understanding of the action of additives that delay or accelerate nucleation and presents a framework within which the nucleation of other ordered protein solid phases, e.g., the sickle cell hemoglobin polymers, can be analyzed.
蛋白质有序固相的成核在实验室、工业以及健康和患病生物体中引发了众多现象。最近对蛋白质晶体的模拟和实验表明，有序晶核的形成之前存在无序的高密度簇，类似于在某些蛋白质中观察到的高密度液滴；这种机制对记录的复杂成核动力学曲线给出了定性解释。在此，我们提出一种简单的唯象理论，该理论考虑了成核过程中的中间高密度亚稳态。利用系统热力学和动力学参数的文献值，以高保真度再现了不同温度和蛋白质浓度下的成核速率数据。我们的计算表明，致密中间体中近临界和超临界有序簇的生长速率是总体成核速率的主要因素。这突出了致密中间体中的粘度对有序核形成的作用。该模型有助于理解延迟或加速成核的添加剂的作用，并提供了一个框架，可用于分析其他有序蛋白质固相的成核，例如镰状细胞血红蛋白聚合物。
