CAJ | 학술논문

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。
목적：연구의제충국지류농약여기류특이성항체적면역식별궤리。방법：채용축보다중선성회귀법연구료의제충국지류농약급기유사물화항체활성（ IC50：반수억제농도）지간적정량구효관계。재계산의제충국지급기유사물결구묘술부적기출상，구건료이유정량구효모형，분석사선영향항체활성적주요인소，병용류일법교차험증료모형적예측능력。동시，채용편최소이승법대계산소득의제충국지분자편단적결구삼수진행료분석，건립료분자아결구화항체활성지간적전식정량구효모형，운용불동안색편마래반영분자편단대항체활성적공헌。결과：이유정량구효모형화전식정량구효모형적결정계수（ R2）분별위0.920화0.917，이자적교차험증계수（ Q2）분별위0.875화0.660，표명량모형구유량호적예측능력。유이유정량구효모형환가득，의제충국지류농약적소수성월소，왕왕화항체적결합능력취월강。차외，재상시료다충분자편단조합후，득도료최우전식정량구효모형，기분자편단적대소재4～10지간，분자편단적장도위61，우화적주성분위4，분자편단적류형위B／C／Ch；단의제충국지류농약지문도보적편마결과화시험결과불완전문합。결론：의제충국지류농약적소수성시영향항체식별적주요인소。
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 ( IC50:fifty percent inhibition 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) cross-validation.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 0.917 individually,cross-validation coefficient ( Q2 ) of two QSAR models were 0.875 and 0.660 respectively ,which showed two models had good predictive abil-ity.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 exper-imental IC50 values.Conclusion:Hydrophobicity of synthetic pyrethroids is the largest correlation factors in antibody recognization .