Bioinformatics Institute, 30 Biopolis Street, #07-01, Matrix, Singapore 138671.
Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543.
Nucleic Acids Res. 2019 Jul 2;47(W1):W482-W489. doi: 10.1093/nar/gkz358.
The study of contact residues and interfacial waters of antibody-antigen (Ab-Ag) structures could help in understanding the principles of antibody-antigen interactions as well as provide guidance for designing antibodies with improved affinities. Given the rapid pace with which new antibody-antigen structures are deposited in the protein databank (PDB), it is crucial to have computational tools to analyze contact residues and interfacial waters, and investigate them at different levels. In this study, we have developed AppA, a web server that can be used to analyze and compare 3D structures of contact residues and interfacial waters of antibody-antigen complexes. To the best of our knowledge, this is the first web server for antibody-antigen structures equipped with the capability for dissecting the contributions of interfacial water molecules, hydrogen bonds, hydrophobic interactions, van der Waals interactions and ionic interactions at the antibody-antigen interface, and for comparing the structures and conformations of contact residues. Various examples showcase the utility of AppA for such analyses and comparisons that could help in the understanding of antibody-antigen interactions and suggest mutations of contact residues to improve affinities of antibodies. The AppA web server is freely accessible at http://mspc.bii.a-star.edu.sg/minhn/appa.html.
研究抗体-抗原（Ab-Ag）结构的接触残基和界面水有助于理解抗体-抗原相互作用的原理，并为设计具有更高亲和力的抗体提供指导。鉴于新的抗体-抗原结构在蛋白质数据库（PDB）中快速积累，拥有分析接触残基和界面水的计算工具，并在不同层次上进行研究至关重要。在这项研究中，我们开发了 AppA，这是一个可用于分析和比较抗体-抗原复合物的接触残基和界面水的三维结构的网络服务器。据我们所知，这是第一个配备有剖析界面水分子、氢键、疏水相互作用、范德华相互作用和离子相互作用在抗体-抗原界面上的贡献的能力，并用于比较接触残基的结构和构象的抗体-抗原结构的网络服务器。各种示例展示了 AppA 用于此类分析和比较的实用性，这有助于理解抗体-抗原相互作用，并提出接触残基的突变以提高抗体的亲和力。AppA 网络服务器可免费访问，网址为 http://mspc.bii.a-star.edu.sg/minhn/appa.html。
