Computational Tools for Protein Crystallization and Structural Analysis

晶体和低温EM结构的确定以及随后的深入结构分析在当前基于合理结构的疫苗设计工作中发挥着关键作用。然而，许多重要靶点的结构，如病毒表面蛋白，已被证明极难用传统的方法如蛋白质结晶和核磁共振来确定。这对基于结构的疫苗设计工作构成了重大障碍，这些工作严重依赖于高质量原子级结构信息的可用性。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的计算工具可以为更适合结晶的蛋白质的分子设计提供合理的基础，从而能够在原子水平上表征原本难以确定的目标。此外，一旦确定了特定靶点的结构，计算工具也可以帮助进行结构分析，帮助提取具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辅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.