DATA类逆转录酶抑制剂的三维定量构效关系

Three Dimensional Quantitative Structure-Activity Relationship of DATA Analogues as HIV-1 Reverse Transcriptase Inhibitors

采用对接方法得到HIV-1抑制剂DATA(二芳基三嗪类)分子的活性构象,进一步用比较分子场分析(CoMFA)和比较分子相似性分析(CoMSIA)法对DATA类逆转录酶抑制剂(RTIs)的三维定量构效关系(3D-QSAR)进行了研究,建立3D-QSAR模型,以指导进一步结构修饰.用此模型预测了5个DATA类似物,预测偏差较小,表明了所建立的模型具有较强的预测能力.

The complex models of a series HIV- 1 RTIs of diaryltriazine （DATA） with HIV- 1 RT have been obtained by employing molecular docking approach. Using the binding conformation of these DATAs, we build 3D-QSAR models from a comparative molecular field analysis （CoMFA） and comparative molecular similarity indices analysis （CoMSIA）. The results indicate a strong correlation between the inhibitory activity of these DATAs and the steric and electrostatic fields around them, which can be used to modify this kind of compound. In order to test the robustness of the models, we randomized the target values for the set of compounds. The deviation between prediction and experiment is small.