Bioinformatics and Biology Insights
Bioinformatics and Biology Insights
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DOI：
10.4137/bbi.s2745
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发表时间：
2009-01
影响因子：
5.8
通讯作者：
W. Braun
中科院分区：
文献类型：
--
作者：
W. Braun
背景中和抗体构象表位的精确测定是合理设计新型疫苗的关键步骤。一个强有力的实验方法，以获得对构象表位的物理化学性质的见解是选择线性肽，结合与高亲和力的单克隆抗体的目的，通过噬菌体展示技术。然而，来自这些模拟表位的构象表位的结构表征并不简单，并且在过去，来自噬菌体展示实验的肽序列的解释集中于线性序列分析以找到共有序列或共同序列基序。结果我们提出了一个全自动的搜索方法，EpiSearch预测构象表位的抗原表面上的可能位置。该算法使用来自噬菌体展示实验的肽序列作为输入，并根据肽和补丁中相似残基的频率分布对所有表面暴露的补丁进行排名。我们已经测试了EpiSearch算法的性能的噬菌体展示实验的六个实验数据集，人表皮生长因子受体-2（HER-2/neu），抗体Bo 2C 11靶向FVIII的C2结构域，抗体mAb 17 b和mAb b12的HIV包膜蛋白gp 120，mAb 13 b5靶向HIV-1衣壳蛋白和SARS冠状病毒刺突蛋白的80 R。在所有这些实施例中，如通过抗体-抗原复合物的X射线晶体结构确定的构象表位在EpiSearch的最高评分块内发现，在大多数情况下覆盖实验观察到的构象表位的超过50%的残基。该程序的输入选项包括将单个肽或一组肽映射到抗原结构上，并且计算结果可以在我们的交互式Web服务器上可视化。可用性用户可以从我们的网络服务器http://curie.utmb.edu/episearch.html访问EpiSearch联系方式webraun@utmb.edu
Background Precise determination of conformational epitopes of neutralizing antibodies represents a key step in the rational design of novel vaccines. A powerful experimental method to gain insights on the physical chemical nature of conformational epitopes is the selection of linear peptides that bind with high affinities to a monoclonal antibody of interest by phage display technology. However, the structural characterization of conformational epitopes from these mimotopes is not straightforward, and in the past the interpretation of peptide sequences from phage display experiments focused on linear sequence analysis to find a consensus sequence or common sequence motifs. Results We present a fully automated search method, EpiSearch that predicts the possible location of conformational epitopes on the surface of an antigen. The algorithm uses peptide sequences from phage display experiments as input, and ranks all surface exposed patches according to the frequency distribution of similar residues in the peptides and in the patch. We have tested the performance of the EpiSearch algorithm for six experimental data sets of phage display experiments, the human epidermal growth factor receptor-2 (HER-2/neu), the antibody mAb Bo2C11 targeting the C2 domain of FVIII, antibodies mAb 17b and mAb b12 of the HIV envelope protein gp120, mAb 13b5 targeting HIV-1 capsid protein and 80R of the SARS coronavirus spike protein. In all these examples the conformational epitopes as determined by the X-ray crystal structures of the antibody-antigen complexes, were found within the highest scoring patches of EpiSearch, covering in most cases more than 50% residues of experimental observed conformational epitopes. Input options of the program include mapping of a single peptide or a set of peptides on the antigen structure, and the results of the calculation can be visualized on our interactive web server. Availability Users can access the EpiSearch from our web server http://curie.utmb.edu/episearch.html Contact webraun@utmb.edu