Computational Algorithms, Methods, and Tools for Structure-Based Vaccine Design

激发针对免疫隐性、隐性或短暂性靶标的抗体是疫苗设计的一个挑战。一个潜在的解决方案是精确的免疫原设计。结构生物学提供抗体-抗原相互作用的原子水平定义和计算生物学操纵蛋白质结构的能力，至少提高了蛋白质抗原精确复制靶抗体识别的抗原表面的可能性。通过将表位移植到外源支架上设计免疫原，以及使用计算技术（称为支架/表位移植和抗原表面修饰）将抗体反应集中到精确位点，最近的成功分别突出了计算生物学可能在疫苗设计中发挥关键作用的概念。然而，越来越多的证据表明，疫苗设计将需要系统地开发与分析、设计、操纵蛋白质结构和蛋白质-蛋白质（或蛋白质-配体）相互作用相关的计算算法、方法和工具，而不是依赖于一组定义良好的工具。在这里，我们讨论了一些预计会影响基于结构的疫苗设计的技术问题。具体来说，我们描述了新的蛋白质设计和结构建模算法，方法和工具的发展，特别适合于疫苗设计。

Elicitation of antibodies against targets that are immunorecessive, cryptic, or transient in their native context is a challenge for vaccine design. One potential solution is precise immunogen design. The ability of structural biology to provide atomic-level definition of antibody-antigen interactions and of computational biology to manipulate protein structure has raised the possibility at least for protein antigens of precisely replicating the antigenic surface recognized by a target antibody. Recent successes in immunogen design by transplanting an epitope to foreign scaffolds and in focusing the antibody response to a precise site using computational techniques, termed scaffolding/epitope-transplantation and antigenic resurfacing, respectively highlight the notion that computational biology may play a crucial role in vaccine design. Rather than relying on a small set of well-defined tools, however, increasing evidence suggests that vaccine design will require the systematic development of computational algorithms, methods, and tools associated with the analysis, design, of manipulation of protein structures and protein-protein (or protein-ligand) interactions. Here we address a number of technological issues that are expected to impact structure-based vaccine design. Specifically, we describe the development of new protein design and structure-modeling algorithms, methods, and tools that are particularly suited for vaccine design.