The relative orientation of the two variable domains, V_H and V_L, influences the shape of the antigen binding site, that is, the paratope, and is essential to understand antigen specificity. ABangle characterizes the V_H‐V_L orientation by using five angles and a distance and compares it to other known structures. Molecular dynamics simulations of antibody variable domains (Fvs) reveal fluctuations in the relative domain orientations. The observed dynamics between these domains are confirmed by NMR experiments on a single‐chain variable fragment antibody (scFv) in complex with IL‐1β and an antigen‐binding fragment (Fab). The variability of these relative domain orientations can be interpreted as a structural feature of antibodies, which increases the antibody repertoire significantly and can enlarge the number of possible binding partners substantially. The movements of the V_H and V_L domains are well sampled with molecular dynamics simulations and are in agreement with the NMR ensemble. Fast Fourier transformation of the ABangle metrics allows to assign timescales of 0.1‐10 GHz to the fastest collective interdomain movements. The results clearly show the necessity of dynamics to understand and characterize the favorable orientations of the V_H and V_L domains implying a considerable binding interface flexibility and reveal in all antibody fragments (Fab, scFv, and Fv) very similar V_H‐V_L interdomain variations comparable to the distributions observed for known X‐ray structures of antibodies.

中文翻译：

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通过计算机模拟和 NMR 观察到的 VH -VL 域间动力学。

两个可变结构域 V _H和 V _L的相对方向影响抗原结合位点（即互补位）的形状，对于理解抗原特异性至关重要。ABangle通过使用五个角度和一个距离来表征 V _H ‐V _{L方向，并将其与其他已知结构进行比较。}抗体可变域 (Fvs) 的分子动力学模拟揭示了相对域方向的波动。在与 IL-1β 和抗原结合片段 (Fab) 复合的单链可变片段抗体 (scFv) 上进行的 NMR 实验证实了这些结构域之间观察到的动态。这些相对结构域方向的可变性可以解释为抗体的结构特征，这显着增加了抗体库，并且可以大大增加可能的结合配偶体的数量。_{V H}和 V _L域的运动通过分子动力学模拟得到了很好的采样，并且与 NMR 系综一致。ABangle 度量的快速傅里叶变换允许将 0.1-10 GHz 的时间尺度分配给最快的集​​体域间移动。结果清楚地表明，需要用动力学来理解和表征 V H 和 V L 结构域的有利方向，_这意味着相当_大的结合界面灵活性，并在所有抗体片段（Fab、scFv 和 Fv）中揭示出非常相似的 V _H ‐VL域间变化与已知抗体 X 射线结构观察到的分布相当。