Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York NY, USA.
Department of Biology, Center for Genomics and Systems Biology and Computer Science Department, Courant Institute of Mathematical Sciences, New York University, New York NY, USA.
Protein Eng Des Sel. 2018 Dec 1;31(12):479-487. doi: 10.1093/protein/gzz007.
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 Try100I is critical to 447 binding affinity.
447-52D（447）是一种人源单克隆抗体，可识别 HIV-1 gp120 第三可变环（V3）中保守的表位，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，我们使用计算突变和建模相结合的方法，结合荧光偏振测定法，研究了 447 CDRH3 长度的分子基础以及选定的 CDRH3 残基对亲和力的个体贡献。我们观察到，447 CDRH3 长度提供了一个大的结合表面积，并且最好的焓贡献来自疏水性堆积、主链氢键、静电和范德华相互作用。我们还发现，CDRH3 残基 Try100I 对 447 的结合亲和力至关重要。
