Modeling the peptide-T cell receptor interaction by the comparative molecular similarity indices analysis-soft independent modeling of class analogy technique
Modeling the peptide-T cell receptor interaction by the comparative molecular similarity indices analysis-soft independent modeling of class analogy technique
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DOI：
10.1021/jm050876m
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发表时间：
2006-04-06
影响因子：
7.3
通讯作者：
Flower, DR
中科院分区：
文献类型：
--
作者：
Doytchinova, IA;Flower, DR
一组38个表位和183个非表位，结合等位基因的HLA-A3超型，进行了比较分子相似性指数分析（CoMSIA）和软独立建模类类比（SIMCA）的组合。在T细胞识别过程中，T细胞受体（TCR）与结合的九聚体肽的中心部分相互作用;因此在研究中仅考虑了位置4-8。在五组交叉验证后，衍生的模型区分了82%的表位和73%的非表位。该模型的总体偏好是具有高电子密度和形成氢键能力的极性氨基酸。这些所谓的“攻击性”氨基酸的侧翼是小尺寸的残基，这使得这些残基能够从结合裂缝突出，并在TCR介导的T细胞识别中发挥积极作用。表位中间部分的“攻击性”和“被动”氨基酸的组合构成推定的TCR结合基序。
A set of 38 epitopes and 183 non-epitopes, which bind to alleles of the HLA-A3 supertype, was subjected to a combination of comparative molecular similarity indices analysis (CoMSIA) and soft independent modeling of class analogy (SIMCA). During the process of T cell recognition, T cell receptors (TCR) interact with the central section of the bound nonamer peptide; thus only positions 4-8 were considered in the study. The derived model distinguished 82% of the epitopes and 73% of the non-epitopes after cross-validation in five groups. The overall preference from the model is for polar amino acids with high electron density and the ability to form hydrogen bonds. These so-called "aggressive" amino acids are flanked by small-sized residues, which enable such residues to protrude from the binding cleft and take an active role in TCR-mediated T cell recognition. Combinations of "aggressive" and "passive" amino acids in the middle part of epitopes constitute a putative TCR binding motif.