Computational Tools for Protein Crystallization and Structural Analysis

晶体结构的解决和深入的结构分析在当前基于抗体的合理疫苗设计的努力中发挥着关键作用。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或核磁共振来确定。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模拟的计算工具可以为编辑后的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其他回避的目标。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，帮助提取其全部生物学意义，并指导新的实验工作。特别是，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 solution of crystal structures and in-depth structural analysis play a pivotal role in current efforts for rational antibody-based vaccine design. However, the structures for many important targets, such as viral surface proteins, haven proven extremely difficult to determine using traditional methods such as protein crystallization or 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 simulation of proteins at different levels of structural detail can provide a rational basis for the molecular design of edited 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 its full biological meaning and to guide new experimental efforts. In particular, here we develop and utilize computational tools to assist in protein crystallization and structural analysis.