TAP-binding peptides prediction by QSAR modeling based on amino acid structural information.
TAP-binding peptides prediction by QSAR modeling based on amino acid structural information.
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基于氨基酸结构信息的 QSAR 模型预测 TAP 结合肽。
DOI：
10.2174/157340912799218499
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发表时间：
2012
影响因子：
1.7
通讯作者：
Zhihua Lin
中科院分区：
文献类型：
--
作者：
Yuanqing Wang;Xiao;Yong Lin;Haixia Wen;Li Wang;Q. Xia;Zhihua Lin
与抗原加工相关的转运蛋白（TAP）对于将肽从胞质溶胶递送到内质网（ER）腔中是必需的，在内质网腔中这些肽被装载在主要组织相容性复合物（MHC）I分子上并形成肽-MHC复合物。肽-MHC离开ER并在细胞表面上向细胞毒性T细胞展示其抗原货物。本研究从AAIndex数据库中收集了89个氨基酸的理化性质，并用于表征与TAP结合的肽。采用逐步回归法（STR）优化TAP结合肽的表征参数，采用多元线性回归法（MLR）构建基于优化参数的定量构效关系（QSAR）模型。定量模型具有较好的信度和预测能力，“留一法”验证的Q²为0.676，检验集的R²为0.722。此外，模型的标准化系数可以显示表位的每个位置的属性，并确定哪个特定的氨基酸适合于肽的任何位置。因此，STR-MLR构建的QSAR模型具有计算简单、解释方便、性能良好、理化指标明确等优点，可用于指导TAP结合肽的设计和修饰。
The transporter associated with antigen processing (TAP) is essential for peptide delivery from the cytosol into the lumen of the endoplasmic reticulum (ER), where these peptides are loaded on a major histocompatibility complex (MHC) I molecules and form peptide-MHC complex. The peptide-MHC leaves the ER and displays their antigenic cargo on the cell surface to cytotoxic T cells. In this study, 89 physicochemical properties of amino acid were collected from AAIndex database, and used to characterize the peptides which were binding to TAP. Then, the stepwise regression (STR) was used to optimize the parameters which characterized the TAP binding peptides, and the multiple linear regression (MLR) was used to construct the quantitative structural activity relationship (QSAR) model based on optimized parameters. The quantitative models had good reliability and predictive ability: the Q² of "leave one out" validation is 0.676 and R² of test dataset is 0.722 respectively. Additionally, the standardized coefficients of the models could demonstrate the attributions for each position of epitope and determine which special amino acid is suitable at any position of the peptide. Therefore, the QSAR model constructed by STR-MLR has many advantages, such as, easier calculation and explanation, good performance, and definite physiochemical indication, which could be used to guide the design and modification of the TAP binding peptide.
影响因子：
32.4
作者：
HEEMELS, MT;PLOEGH, HL
通讯作者：
PLOEGH, HL