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用分子对接方法研究了一系列芳香二酮酸类抑制剂与HIV-1整合酶的识别及相互作用.结果表明,抑制剂结合到整合酶Asp64～Leu68,Thr115～Phe121,Gln148～Lys159和Mg2+所构成的口袋区,抑制机理与5CITEP相似.采用分子动力学模拟和MM/PBSA方法计算了芳香二酮酸类抑制剂与整合酶之间的结合自由能,计算结果与实验值相吻合,平均绝对偏差为3.6kJ/mol,体系范德华相互作用和溶剂化效应的非极性项是利于形成复合物的主要因素.相关性分析结果表明,结合自由能值与疏水相互作用有较强的线性相关(R=0.61),基于此,用多元线性回归方法给出了一个能较强预测芳香二酮酸类抑制剂与HIV-1整合酶的结合自由能预测模型,为后续基于抑制剂结构的抗HIV-1药物分子设计提供指导.
The molecular docking method was used to study the recognition and interaction between a series of aromatic diketonic acid inhibitors and HIV-1 integrase. The results showed that the inhibitors bind to Asp64 ~ Leu68, Thr115 ~ Phe121, Gln148 ~ Lys159 and Mg2 + And the inhibitory mechanism was similar to that of 5CITEP.The free energy of binding between aromatic diketonic acid inhibitors and integrase was calculated by molecular dynamics simulation and MM / PBSA method.The calculated results were in good agreement with the experimental data, and the average absolute The non-polar term of van der Waals interactions and solvation effect of the system is the main factor contributing to the formation of the complex.The correlation analysis shows that there is a strong linear correlation between the binding free energy and hydrophobic interaction R = 0.61). Based on this, a predictive model of binding free energy of aromatic diketonic acid inhibitors and HIV-1 integrase was proposed by using the multiple linear regression method. -1 drug molecule design to provide guidance.