The interfacial character of antibody paratopes: analysis of antibody-antigen structures
The interfacial character of antibody paratopes: analysis of antibody-antigen structures
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DOI：
10.1093/bioinformatics/btx389
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发表时间：
2017-10-01
期刊：
影响因子：
5.8
通讯作者：
Zhong, Pingyu
中科院分区：
文献类型：
--
作者：
Nguyen, Minh N.;Pradhan, Mohan R.;Zhong, Pingyu
在这项研究中，应用计算方法研究了来自403个抗体-抗原复合体的非冗余数据集中的抗原结合残基的一般性质，以剖析氢键、疏水、van der Waals接触和离子相互作用的贡献，以及水分子在抗原-抗体界面中的作用。与以前使用较小数据集的报告一致，我们发现Tyr、Trp、Ser、Asn、Asp、Thr、Arg、Gly、His对抗体和抗原之间的相互作用有很大贡献。此外，抗体-抗原的相互作用可以通过界面水来调节。然而，目前还没有关于大量在抗体-抗原界面参与更高有序结构的结构化水的全面分析的报道。从我们的数据集，我们已经发现242个络合物中存在界面水。我们提出的证据表明，这些界面水在抗体与一系列形状互补性不同的抗原的相互作用中发挥着令人信服的作用。最后，我们使用CLICK方法对来自我们的数据集的抗体与其界面水分子的771个接触残基的结构进行了296835个成对的3D结构比较。使用启发式聚类算法来获得唯一的结构相似性，并发现将其划分为368个不同的簇。这些簇被用来识别与表位结合的抗体的接触残基的结构基序。
In this study, computational methods are applied to investigate the general properties of antigen engaging residues of a paratope from a non-redundant dataset of 403 antibody-antigen complexes to dissect the contribution of hydrogen bonds, hydrophobic, van der Waals contacts and ionic interactions, as well as role of water molecules in the antigen- antibody interface. Consistent with previous reports using smaller datasets, we found that Tyr, Trp, Ser, Asn, Asp, Thr, Arg, Gly, His contribute substantially to the interactions between antibody and antigen. Furthermore, antibody-antigen interactions can be mediated by interfacial waters. However, there is no reported comprehensive analysis for a large number of structured waters that engage in higher ordered structures at the antibody- antigen interface. From our dataset, we have found the presence of interfacial waters in 242 complexes. We present evidence that suggests a compelling role of these interfacial waters in interactions of antibodies with a range of antigens differing in shape complementarity. Finally, we carry out 296 835 pairwise 3D structure comparisons of 771 structures of contact residues of antibodies with their interfacial water molecules from our dataset using CLICK method. A heuristic clustering algorithm is used to obtain unique structural similarities, and found to separate into 368 different clusters. These clusters are used to identify structural motifs of contact residues of antibodies for epitope binding.