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Abstract：
We present here a case study of an antibody-engineering platform that selects, modifies, and assembles antibody parts to construct novel antibodies. A salient feature of this platform includes the role of amino acid networks in optimizing framework regions (FRs) and complementarity determining regions (CDRs) to engineer new antibodies with desired structure-function relationships. The details of this approach are described in the context of its utility in engineering ZAb_FLEP, a potent anti-Zika virus antibody. ZAb_FLEP comprises of distinct parts, including heavy chain and light chain FRs and CDRs, with engineered features such as loop lengths and optimal epitope-paratope contacts. We demonstrate, with different test antibodies derived from different FR-CDR combinations, that despite these test antibodies sharing high overall sequence similarity, they yield diverse functional readouts. Furthermore, we show that strategies relying on one dimensional sequence similarity-based analyses of antibodies miss important structural nuances of the FR-CDR relationship, which is effectively addressed by the amino acid networks approach of this platform.
摘要：
我们在这里提供一个抗体工程平台的案例研究，修改,并组装抗体部分以构建新型抗体。该平台的显着特征包括氨基酸网络在优化框架区（FR）和互补决定区（CDR）中的作用，以工程化具有所需结构-功能关系的新抗体。这种方法的细节在其在工程ZAb_FLEP，一种有效的抗寨卡病毒抗体.ZAb_FLEP由不同的部分组成，包括重链和轻链FR和CDR，具有工程特征，如环长度和最佳表位互补接触。我们证明,来自不同FR-CDR组合的不同测试抗体，尽管这些测试抗体具有很高的整体序列相似性，它们产生不同的功能读数。此外，我们表明，依赖于基于一维序列相似性的抗体分析的策略错过了FR-CDR关系的重要结构细微差别，这个平台的氨基酸网络方法有效地解决了这个问题。
