利用CoMFA和CoMSIA对氟乐灵抗体识别特异性进行3D-QSAR分析  

3D-QSAR Analysis of Trifluralin Antibody Recognition Specificity Using CoMFA and CoMSIA

作　　者：李嘉宜 姚茜 黄惠威 施迪燊 刘凤银[1] 黄新安[2] 袁学文[1] 杨剑萍[1] 穆洪涛[1] Li Jiayi;Yao Xi;Huang Huiwei;Shi Dishen;Liu Fengyin;Huang Xinan;Yuan Xuewen;Yang Jianping;Mu Hongtao(Guangdong University of Education,Guangzhou,Guangdong 510303,China;Artemisinin Research Center,Guangzhou University of Chinese Medicine,Guangzhou,Guangdong 510405,China)

机构地区：[1]广东第二师范学院生物与食品工程系,广东广州510303 [2]广州中医药大学中药学系,广东广州510405

出　　处：《化学世界》2024年第4期226-232,共7页Chemical World

摘　　要：为了探究氟乐灵多克隆抗体PcAb-2C识别特异性与药物分子三维结构的定量关系,利用PcAb-2C的交叉反应数据,选取比较分子力场分析法(CoMFA),比较分子相似指数法(CoMSIA)进行三维定量构效关系(3D-QSAR)研究,并建立相应的模型。结果表明:CoMFA模型的交叉验证系数(r_(cv)^(2))为0.497,非交叉验证系数(r_(ncv)^(2))为0.999;CoMSIA模型的交叉验证系数(r_(cv)^(2))为0.498,非交叉验证系数(r_(ncv)^(2))为0.979。CoMFA模型中立体场和静电场的贡献值分别为63.10%和36.90%,CoMSIA模型中疏水场、静电场和立体场的贡献值分别为54.90%、38.40%和6.70%。各力场的贡献比例表明基团的疏水作用对化合物影响较大,推测出抗原疏水性的增强特别是N,N-二丙基部位的疏水性增强,有利于诱导出亲和力更强的抗体,为设计氟乐灵半抗原提供了信息。To investigate the quantitative relationship between the recognition specificity of trifluralin polyclonal antibody PcAb-2C and three-dimensional structure of drug molecules,the cross-reactivity data of PcAb-2C were collected in this paper.The three-dimensional quantitative structure-activity relationship(3D-QSAR)was studied in this research by combining molecular force field analysis(CoMFA)and comparative molecular similarity index(CoMSIA),and then a matching model was developed.The results showed that the cross-validation coefficient(r_(cv)^(2))of CoMFA model was 0.497 and non-cross-validation coefficient(r_(ncv)^(2))was 0.999.The cross-validation coefficient(r_(cv)^(2))was 0.498 and non-cross-validation coefficient(r_(ncv)^(2))was 0.979 for CoMSIA model.The contributions of steric and electrostatic fields in CoMFA model were 63.10%and 36.90%,respectively,and the contributions of hydrophobic,electrostatic and steric fields in CoMSIA model were 54.90%,38.40%and 6.70%,respectively.The contribution ratio of each force field indicated that the hydrophobic effect of the moiety had a significant impact on the molecule.It was hypothesized that the enhanced hydrophobicity of the antigen,especially at the N,N-dipropyl site,facilitated the induction of antibodies with stronger affinity,providing information for the design of trifluralin hapten.

关 键 词：氟乐灵 多克隆抗体 比较分子力场分析法 比较分子相似性指数分析 

分 类 号：TQ463[化学工程—制药化工]