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HIV-1逆转录酶抑制剂是鸡尾酒疗法,即高效抗逆转录病毒治疗的主要组成成分,S-DABO系列化合物及其类似骨架对HIV-1逆转录酶表现出良好的抑制活性.本文基于公共骨架叠合的方法生成了基于场的三维定量构效关系模型(Field-based QSAR model),并通过高斯立体场、静电场、疏水场、氢键供体场、氢键受体场和芳环场来表征.对应的统计学参数训练集交叉验证相关系数R2CV为0.5949,相关系数R2为0.8421,测试集Q2为0.5486,测试集相关系数Pearson-r为0.7460.通过分子对接,分子结合口袋分析以及三维等势图分析,我们得到了关键的药效基团与相互作用:(i)化合物与氨基酸残基Tyr181,Tyr188,Trp229存在π-π相互作用,与His236之间存在σ-π相互作用;(ii)化合物与Lys101之间存在氢键,与Tyr188之间存在卤键.对接分析和Field-based QSAR模型可以为新型HIV-1逆转录酶抑制剂的设计提供借鉴和帮助.“,”HIV-1 reverse transcriptase (RT) inhibitors are major components of HAART (highly active antiviral therapy).The S-DABOs (dihydro-alkylthio-benzyl-oxopyrimidines) series and their similar skeletons have exhibited preferable activities to inhibit HIV-1 RT.In the present study,we generated field-based QSAR models using common structure alignment,which was characterized by Gaussian steric,electrostatic,hydrophobic,hydrogen bond donor,hydrogen bond acceptor and aromatic ring fields (R2=0.8421,R2cv =0.5949 for the training set,Q2=0.5486,Pearson-r =0.7460 for the test set).Docking,pocket surface and contour map analyses were carried out.Key pharmacophore features were investigated,including (i) π-π interaction with residue Tyrl 81,Tyr188 and Trp229,σ-π interaction with His236,(ii) hydrogen bond with residue Lys101 and halogen bond with residue Tyr188.The docking analysis and field-based QSAR models could provide reasonable guidance in the rational design of potent HIV-1 RT inhibitors.