A Comparative Molecular Similarity Index Analysis (CoMSIA) study identifies an HLA-A2 binding supermotif
A Comparative Molecular Similarity Index Analysis (CoMSIA) study identifies an HLA-A2 binding supermotif
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DOI：
10.1023/a:1021917203966
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发表时间：
2002-08-01
影响因子：
3.5
通讯作者：
Flower, DR
中科院分区：
文献类型：
--
作者：
Doytchinova, IA;Flower, DR
将3D-QSAR CoMSIA技术应用于与五种最广泛的HLA-A2样等位基因A*0201、A*0202、A*0203、A*0206和A*6802结合的一组458个肽。包括主要的物理化学性质（空间体积，电子密度，疏水性和氢键形成能力）的模型得到了可接受的预测（q（2）范围从0.385到0.683）。使用系数等值线图允许A2-超基序被确定的基础上共同的有利和不利的地区。最佳HLA-A2结合剂的CoMSIA定义如下：1位的疏水性芳族氨基酸; 2、6和9位的疏水性大侧链; 3位的非氢键形成氨基酸; 4位的小脂族氢键供体; 5位的脂族氨基酸; 7位的小脂族侧链;和在位置8的小的脂族亲水性和氢键形成氨基酸。
The 3D-QSAR CoMSIA technique was applied to a set of 458 peptides binding to the five most widespread HLA-A2-like alleles: A*0201, A*0202, A*0203, A*0206 and A*6802. Models comprising the main physicochemical properties (steric bulk, electron density, hydrophobicity and hydrogen-bond formation abilities) were obtained with acceptable predictivity (q(2) ranged from 0.385 to 0.683). The use of coefficient contour maps allowed an A2-supermotif to be identified based on common favoured and disfavoured areas. The CoMSIA definition for the best HLA-A2 binder is as follows: hydrophobic aromatic amino acid at position 1; hydrophobic bulky side chains at positions 2, 6 and 9; non-hydrogen-bond-forming amino acids at position 3; small aliphatic hydrogen-bond donors at position 4; aliphatic amino acids at position 5; small aliphatic side chains at position 7; and small aliphatic hydrophilic and hydrogen-bond forming amino acids at position 8.