Nonclassical Nucleation Pathways and Growth Kinetics of Protein Crystallization

虽然经典成核理论已经在许多系统中取得了成功，但最近对蛋白质和胶体结晶以及生物矿化的研究显示出在成核早期阶段的非经典特征。非经典机制表明，在初始溶液和最终结晶状态之间存在中间相（团簇或致密液相），而不是直接从过饱和溶液形成核。然而，在实践中，预测特定系统在特定条件下遵循的确切路径仍然是一个挑战。我们最近的研究（Sauter等）。j。化学。Soc. 2015, 137, 1485)可以作为实时研究的原理证明，通过生长动力学的细节来识别成核途径。在这个提议中，我们的目的是利用蛋白质-盐模型系统来探索非经典的成核和生长途径。通过对几种蛋白质在多价金属离子存在下的结晶进行系统的实时研究，我们的目标是提供成核动力学的系统结果，各种中间体在成核和生长中的作用，我们期望建立结晶途径与微观特异性和非特异性相互作用之间的关系。

While classical nucleation theory has been successful in many systems, recent studies of protein and colloid crystallization as well as biomineralization have shown nonclassical features in the early stage of nucleation. Instead of forming nuclei directly from the supersaturated solution, the nonclassical mechanism suggests an intermediate phase (clusters or a dense liquid phase) to exist between the initial solution and the final crystalline state. In practice, however, predicting the exact pathway followed by a specific system under specific conditions is still a challenge. Our recent study (Sauter, et al. J. Am. Chem. Soc. 2015, 137, 1485) serves as a proof of principle of a real-time study to identify the nucleation pathway by the details of growth kinetics. In this proposal, we aim to explore the nonclassical nucleation and growth pathway using a protein-salt model system. By performing a systematic real-time study of crystallization of several proteins in the presence of multivalent metal ions, we aim to provide systematic results on the nucleation kinetics, the role of various intermediates on nucleation and growth, and we expect to establish the relationship between the crystallization pathways and microscopic specific and nonspecific interactions.