The recognitions and interactions of a series of aryl diketoacid (ADK) inhibitors with HIV-1 integrase (IN) were studied via molecular docking method. The results indicate that the inhibitors bind to the pocket (formed by Asp64～Leu68, Thr115～Phe121, Gln148～Lys159 and Mg2＋ ion) of IN, and the inhibiting mechanism is similar to that of 5CITEP. Molecular dynamics simulation and MM/PBSA methods were used to calculate the binding free energy between ADK inhibitors and IN. The calculated binding free energy agrees well with experimental data, and the average absolute deviation is 3.6 kJ/mol. It was also found that the formation of the complex was mainly driven by the favorable van der Waals’(VDW) interactions in the system and the favorable non-polar item of the solvent effect. Correlation analysis shows that the binding free energy has obvious linear correlation with the hydrophobic interaction (R＝0.61), from which a good model predicting the binding free energy of ADK inhibitors with HIV-1 IN has been obtained through a multiple linear regression method. All the above simulation results provide us with some helpful instruction for the anti-HIV drug design based on the structures of inhibitors.

Key words: aryl diketoacid, integrase, binding free energy, correlation, molecular design