拟除虫菊酯类农药-抗体活性定量构效关系研究

Quantitative structure-activity relationship of synthetic pyrethroids and antibody activity

目的：研究拟除虫菊酯类农药与其类特异性抗体的免疫识别机理。方法：采用逐步多重线性回归法研究了拟除虫菊酯类农药及其类似物和抗体活性（IC50：半数抑制浓度）之间的定量构效关系。在计算拟除虫菊酯及其类似物结构描述符的基础上,构建了二维定量构效模型,分析筛选影响抗体活性的主要因素,并用留一法交叉验证了模型的预测能力。同时,采用偏最小二乘法对计算所得拟除虫菊酯分子片段的结构参数进行了分析,建立了分子亚结构和抗体活性之间的全息定量构效模型,运用不同颜色编码来反映分子片段对抗体活性的贡献。结果：二维定量构效模型和全息定量构效模型的决定系数（R2）分别为0.920和0.917,二者的交叉验证系数（Q2）分别为0.875和0.660,表明两模型具有良好的预测能力。由二维定量构效模型还可得,拟除虫菊酯类农药的疏水性越小,往往和抗体的结合能力就越强。此外,在尝试了多种分子片段组合后,得到了最优全息定量构效模型,其分子片段的大小在4~10之间,分子片段的长度为61,优化的主成分为4,分子片段的类型为B/C/Ch;但拟除虫菊酯类农药指纹图谱的编码结果和试验结果不完全吻合。结论：拟除虫菊酯类农药的疏水性是影响抗体识别的主要因素。

Objective： To research on the immune recognition mechanism of synthetic pyrethroids and generic specific antibody. Methods： We studied on quantitative structure-activity relationship （QSAR） of synthetic pyrethroids and their analogs as well as antibody activity （ICso：fifty percent iithibition concentration） using stepwise multiple linear regression method. Based on calculating structure descriptors of synthetic pyrethroids and their analogs, two-demensional QSAR （2D-QSAR） model was established. The main factors affecting antibody activity were screened using 2D-QSAR, and predictive ability of QSAR models were evaluated by the method of ＂ leave-one-out＂ （ LOO ） crossvalidation. Meanwhile, the structure parameters of synthetic pyrethroid fragments were calculated and then analyzed using partial least squares （PLS） assay. And then hologram QSAR（H-QSAR） model was constructed on molecular substructure and antibody activity. The fragments contribution to antibody activity were illustrated by encoding different colors. Results ： Decision coefficent （ R2 ） of 2D-QSAR model and HQSAR model were 0. 920 and O. 917 individually, crossvalidation coefficient （Q~） of two QSAR models were 0. 875 and O. 660 respectively ,which showed two models had good predictive ability. The result from 2D-QSAR model was also obtained that smaller was hydrophobicity of pyrethroids, easier was recognized by antibody. In addition,the optimum HQSAR model was constructed after we tried many combinations of these parameters. The fragment size in optimum HQSAR model was between 4 to 10, a hologram length was 61, optimum principle component was 4, and the fragment type of B/C/Ch was selected. However, the fingerprint encoded results of synthetic pyrethroids weren＇t consistent completely with experimental IC50 values. Conclusion： Hydrophobicity of synthetic pyrethroids is the largest correlation factors in antibody recognization.