HIV-1 IN integrates viral DNA into host cells through two-steps metal ions-dependent reactions. The number of metal ions binding with HIV-1 IN has very important influence on interactions between HIV-1 IN and inhibitors. At present, two HIV-1 IN dimer core structures (1Mg-IN-Core and 2Mg-IN-Core models) having one or two Mg2+ icons in each catalytic core domain were built in homology modeling methods. Docking them respectively with inhibitor thiazolothiazepines using the program Autodock, complexes with low energy were found. The two kinds of complex structures were compared. Docking results indicate that if the number of Mg2+ binding with IN changed, the interactional modes of IN and thiazolothiazepines will also change; thiazolothiazepines have highly binding specialty and stability with IN; the Mg2+ chelated with ASP64 and GLU152 simultaneously has great influence on IN binding with thiazolothiazepines. A 2000 ps molecular dynamics simulation was carried out on the 2Mg-IN-Core and thiazolothiazepines complex system. Analyzing the MD result, it is found that the metal ions Mg2+ chelated with ASP64 and ASP116 at the same time can form four stable chelate bonds with residues of IN, and the Mg2+ chelated with ASP64 and GLU152 simultaneously can bind with IN, and can make stable coordinate bonds with the inhibition. The latter Mg2+ ion has strong influence on IN stably binding with thiazolothiazepines.

Key words: HIV-1 integrase, Metal ions, Thiazolothiazepines, Molecular simulation