• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >Energy-based analysis and prediction of the orientation between light- and heavy-chain antibody variable domains.
【24h】

Energy-based analysis and prediction of the orientation between light- and heavy-chain antibody variable domains.

机译：基于能量的轻链和重链抗体可变域之间取向的分析和预测。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Diversity in antibody structure is crucial to the ability of the adaptive immune system to recognize the tremendously diverse set of potential antigens. The diversity in structure is most apparent in the six hypervariable loops of the complementarity-determining regions. However, given that these loops occur at the interface of the heavy- and light-chain variable domains and form the antigen-binding site, the relative orientation of the heavy- and light-chain variable domains can create another source of structural diversity leading to changes in antigen binding. Here, we first reexamine the diversity of V(L):V(H) orientations in existing antibody crystal structures using 153 nonredundant sequences, demonstrating that the variation in V(L):V(H) orientation is greater than that expected from effects of crystal packing, antigen binding, or the presence of antibody constant regions and increases, on average, as sequence similarity decreases for residues in the interface between the domains. We developed a tool for predicting the relative orientations of the heavy- and light-chain variable domains using side-chain rotamer sampling in the interface and molecular-mechanics-based energy calculations. When using variable domain backbones from the crystal structures, the predicted orientation is very close (<1 A RMSD) to the crystallographically observed orientation in most cases, confirming that the V(L):V(H) orientation is determined by the antibody sequence and suggesting an approach to predicting the relative orientation of the variable domains when building homology models of antibodies. When applied to antibody homology models generated from templates with 55-75% sequence identity, we predict the V(L):V(H) orientation of 20 antibodies with an average/median RMSD of 2.1/1.6 A to the crystal structures.
机译：抗体结构的多样性对于适应性免疫系统识别多种多样的潜在抗原的能力至关重要。结构的多样性在互补决定区的六个高变环中最为明显。但是，鉴于这些环出现在重链和轻链可变域的界面并形成抗原结合位点，因此，重链和轻链可变域的相对方向会产生另一种结构多样性，从而导致抗原结合的变化。在这里，我们首先使用153个非冗余序列重新检查了现有抗体晶体结构中V（L）：V（H）方向的多样性，证明了V（L）：V（H）方向的变化大于预期的效应晶体堆积，抗原结合或抗体恒定区的存在的平均值，并且随着结构域之间界面中残基的序列相似性降低而平均增加。我们开发了一种工具，用于在界面和基于分子力学的能量计算中使用侧链旋转异构体采样来预测重链和轻链可变域的相对方向。当使用来自晶体结构的可变域主链时，在大多数情况下，预测的方向与晶体学观察到的方向非常接近（<1 A RMSD），这证实了V（L）：V（H）方向是由抗体序列决定的并提出了一种在构建抗体同源性模型时预测可变域的相对方向的方法。当应用于由具有55-75％序列同一性的模板生成的抗体同源性模型时，我们预测20种抗体的V（L）：V（H）方向与晶体结构的平均/中值RMSD为2.1 / 1.6A。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号