The amount of antibody (Ab) variable gene sequence information is expanding rapidly, but our ability to predict the function of Abs from sequence alone is limited. Here, we describe a sequence-to-function prediction method that couples structural data for a single Ab/antigen (Ag) complex with repertoire data. We used a position-specific structure-scoring matrix (P3SM) incorporating structure-prediction scores from Rosetta to identify Ab variable loops that have predicted structural similarity to the influenza virus-specific human Ab CH65. The P3SM approach identified new members of this Ab class. Recombinant Ab expression, crystallography, and virus inhibition assays showed that the HCDR3 loops of the newly identified Abs possessed similar structure and antiviral activity as the comparator CH65. This approach enables discovery of new human Abs with desired structure and function using cDNA repertoires that are obtained readily with current amplicon sequencing techniques.

抗体（Ab）可变基因序列信息的数量正在迅速扩大，但我们仅从序列预测抗体功能的能力是有限的。在这里，我们描述了一种序列到功能的预测方法，该方法将单个 Ab/抗原 (Ag) 复合物的结构数据与曲目数据相结合。我们使用位置特异性结构评分矩阵 (P3SM) 结合 Rosetta 的结构预测评分来识别与流感病毒特异性人类 Ab CH65 具有预测结构相似性的 Ab 可变环。P3SM 方法确定了这个 Ab 类的新成员。重组抗体表达、晶体学和病毒抑制试验表明，新鉴定的抗体的 HCDR3 环具有与比较剂 CH65 相似的结构和抗病毒活性。