Prediction of HLA-DQ3.2beta ligands: evidence of multiple registers in class II binding peptides.
Prediction of HLA-DQ3.2beta ligands: evidence of multiple registers in class II binding peptides.
复制标题
HLA-DQ3.2beta 配体的预测：II 类结合肽中多个寄存器的证据。
DOI：
10.1093/bioinformatics/btl071
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Ranganathan,Shoba
中科院分区：
文献类型：
--
作者：
Tong,JooChuan;Zhang,GuangLan;Tan,TinWee;August,JThomas;Brusic,Vladimir;Ranganathan,Shoba
动机：虽然处理MHC-II类抗原以呈递给辅助T细胞是正常免疫反应所必需的，但它也与自身免疫性疾病和超敏反应的发病机制有关。基于序列的计算技术在预测人类白细胞抗原-DQ结合多肽方面取得了有限的成功，利用三维模型开发的预测技术很少。方法：我们描述了一个基于结构的预测模型来模拟多肽-DQ3.2β复合体。我们已经开发了一种快速而准确的方法将候选肽对接到DQ3.2β受体上，并开发了一种从背景中区分结合物的评分功能。结果：与实验数据相比，该模型预测DQ3.2β结合多肽的准确率较高[受试者工作特征曲线下面积(AROC>；0.90)]。我们研究了DQ3.2β多肽的结合模式，并证明在一个候选结合肽中存在几个注册表。进一步的分析表明，具有多个注册表的多肽主要是为了获得高亲和力的binders.Contact:shoba@els.mq.edu.auSupplementary信息：补充数据可在生物信息学在线上获得。
Motivation:While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models.Methods:We describe a structure-based prediction model for modeling peptide-DQ3.2βcomplexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2βreceptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2βbinding and non-binding peptides obtained from biochemical and functional studies.Results:Our model predicts DQ3.2βbinding peptides with high accuracy [area under the receiver operating characteristic (ROC) curveAROC> 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2βpeptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.Contact:shoba@els.mq.edu.auSupplementary information:Supplementary data is available atBioinformaticsonline.