447-52D (447) is a human monoclonal antibody that recognizes a conserved epitope in the crown region of the third variable loop (V3) of HIV-1 gp120, and like many anti-HIV-1 antibodies with broad neutralization capabilities, it has a long heavy-chain complementarity determining region (CDRH3). Here, we use a combination of computational mutagenesis and modeling in tandem with fluorescence polarization assays to interrogate the molecular basis of 447 CDRH3 length and the individual contribution of selected CDRH3 residues to affinity. We observe that 447 CDRH3 length provides a large binding surface area and the best enthalpic contributions derived from hydrophobic packing, main-chain hydrogen bonds, electrostatic and van der Waals interactions. We also found out that CDRH3 residue Try^100I is critical to 447 binding affinity.

中文翻译：

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计算指导确定447-52D长CDRH3的功能

447-52D（447）是一种人类单克隆抗体，可识别HIV-1 gp120第三可变环（V3）冠状区域中的保守表位，与许多具有广泛中和能力的抗HIV-1抗体一样，它具有长的重链互补决定区（CDRH3）。在这里，我们结合使用荧光诱变和计算诱变与建模相结合的方法来探究447 CDRH3长度的分子基础以及所选CDRH3残基对亲和力的单独贡献。我们观察到447 CDRH3的长度提供了很大的结合表面积，并且最佳疏水焓，疏水性主链氢键，静电和范德华相互作用产生了最佳的焓贡献。我们还发现CDRH3残留物尝试^100I 对447结合亲和力至关重要。