Computational Tools for Protein Crystallization and Structural Analysis

晶体和Cryo-EM结构的确定以及随后的深入结构分析在当前合理的基于结构的疫苗设计中起着关键作用。然而，许多重要靶点（如病毒表面蛋白）的结构已被证明极难使用传统方法（如蛋白质结晶和核磁共振）确定。这对基于结构的疫苗设计工作构成了重大障碍，这在很大程度上依赖于高质量原子水平结构信息的可用性。计算工具允许在不同结构细节水平上对蛋白质进行建模和分子动力学模拟，可以为更适合结晶的蛋白质分子设计提供合理的基础，从而使原子水平表征其他难以逃避的目标。此外，一旦确定了特定靶点的结构，计算工具还可以协助进行结构分析，帮助提取有生物学意义的数据，并指导新的实验工作。在这里，我们开发和利用计算工具来协助蛋白质结晶和结构分析。

The determination of crystal and Cryo-EM structures and subsequent in-depth structural analysis play a pivotal role in current efforts for rational structure-based vaccine design. However, the structures for many important targets, such as viral surface proteins, have proven extremely difficult to determine using traditional methods such as protein crystallization and NMR. This presents a significant obstacle to structure-based vaccine design efforts, which rely heavily on the availability of high-quality atomic-level structural information. Computational tools that allow modeling and molecular dynamics simulation of proteins at different levels of structural detail can provide a rational basis for the molecular design of proteins more suitable for crystallization, thus enabling atomic-level characterization of otherwise evasive targets. Moreover, once the structure of a particular target is determined, computational tools can also assist in structural analysis, to help extract biologically meaningful data and to guide new experimental efforts. Here we develop and utilize computational tools to assist in protein crystallization and structural analysis.