Use of amino acid composition to predict epitope residues of individual antibodies
Use of amino acid composition to predict epitope residues of individual antibodies
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DOI：
10.1093/protein/gzq014
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发表时间：
2010-06-01
影响因子：
2.4
通讯作者：
Hirayama, Noriaki
中科院分区：
文献类型：
--
作者：
Soga, Shinji;Kuroda, Daisuke;Hirayama, Noriaki
我们从蛋白质数据库中确定了非冗余合格抗原-抗体复合物结构中抗原-抗体相互作用界面上的特定氨基酸倾向。用出现在复合物界面上的20 × 20个标准氨基酸对中的每一个的频率来表示倾向性，并命名为抗体特异性表位倾向性（ASEP）指数。利用该指数，我们建立了一种新的预测单个抗体表位残基的方法，通过缩小候选表位残基的范围来预测常规方法预测的候选表位残基。74种基准抗原用于ASEP预测。采用留一法对该方法的效率进行了评价。在所有测量的最低10%的ASEP指数残基消除后，49种抗原的真阳性被富集。随后去除ASEP指数最低的50%的残基，74种抗原中有40种被富集为真阳性。ASEP指数是第一个用于预测单个抗体表位残基的基准。与突变实验结合使用，该指数有可能显著提高表位分析的成功率。
We identified specific amino acid propensities at the interfaces of antigen-antibody interactions in non-redundant qualified antigen-antibody complex structures from Protein Data Bank. Propensities were expressed by the frequency of each of the 20 x 20 standard amino acid pairs that appeared at the interfaces of the complexes and were named the antibody-specific epitope propensity (ASEP) index. Using this index, we developed a novel method of predicting epitope residues for individual antibodies by narrowing down candidate epitope residues which was predicted by the conventional method. The 74 benchmarked antigens were used in ASEP prediction. The efficiency of this method was assessed using the leave-one-out approach. On elimination of residues with ASEP indices in the lowest 10% of all measured, true positives were enriched for 49 antigens. On subsequent elimination of residues with ASEP indices in the lowest 50%, true positives were enriched for 40 of the 74 antigens assessed. The ASEP index is the first benchmark proposed to predict epitope residues for an individual antibody. Used in combination with mutation experiments, this index has the potential to markedly increase the success ratio of epitope analysis.