Computational Tools for Protein Crystallization and Structural Analysis

蛋白质结晶和结构分析的计算工具

• 批准号: 10273040
• 负责人: Gwo-Yu Chuang
• 金额: $ 14.34万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10273040
• 关键词: Biological; Computational Biology; Crystallization; Data; Goals; Hydrophobicity; Link; Membrane Proteins; Methods; Modeling; Molecular; Play; Protein Engineering; Proteins; Role; Site; Solvents; Structure; Surface; Vaccine Design; Viral; Viral Antigens; base; bioinformatics tool; computerized tools; disulfide bond; flexibility; glycosylation; molecular dynamics

The solution of crystal structures and 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.

晶体结构的解决方案和深入的结构分析在当前基于合理结构的疫苗设计中发挥着关键作用。然而，事实证明，使用蛋白质结晶和核磁共振等传统方法极难确定许多重要靶标（例如病毒表面蛋白）的结构。这给基于结构的疫苗设计工作带来了重大障碍，因为这种设计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，从而能够对其他难以回避的目标进行原子级表征。此外，一旦确定了特定靶标的结构，计算工具还可以协助结构分析，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，我们开发并利用计算工具来协助蛋白质结晶和结构分析。