Song Wei, Chen Weizu, Zhang Xiaoyi, Wang Cunxin. Prediction of the Interaction of HIV-1 Integrase and Inhibitor Aurintricarboxylic Acid Using Docking[J]. Chinese Journal of Chemical Physics , 2003, 16(4): 257-260. doi: 10.1088/1674-0068/16/4/257-260
Citation: Song Wei, Chen Weizu, Zhang Xiaoyi, Wang Cunxin. Prediction of the Interaction of HIV-1 Integrase and Inhibitor Aurintricarboxylic Acid Using Docking[J]. Chinese Journal of Chemical Physics , 2003, 16(4): 257-260. doi: 10.1088/1674-0068/16/4/257-260

Prediction of the Interaction of HIV-1 Integrase and Inhibitor Aurintricarboxylic Acid Using Docking

doi: 10.1088/1674-0068/16/4/257-260
  • Received Date: 2002-07-25
  • A docking approach is proposed for the prediction of the interaction of HIV-1 integrase(IN) and inhibitor aurintricarboxylic acid. In order to clarify the function of metal ions on the binding process, we chose two kinds of integrase receptors (one with an Mg+2and another without Mg+2) and performed docking with aurintricarboxylic acid respectively. The receptor structure used for docking was made by the following processes. Because there is no report on the three-dimensional structure of IN/aurintricarboxylic acid complex, the only known crystals structure of the complex of the HIV-1 integrase core domain with an inhibitor 5CITEP(PDB code 1QS4) was referenced, and the monomer coordinate(chain A) was selected. Then, the lacked residues from number 141 to 144 were added by using Insight II. The final structure after 200 ps molecular dynamics simulation was used as the receptor structure for docking. The flexibility of the small molecule was allowed through rotating its dihedrals. The genetic algorithm was used and the empirical potential was taken as an energy score function when docking was being done. All possible conformations were searched throughout the full configuration space. The results of our study illustrate that the ion Mg+2 is important for the stability of the binding of the ligand and receptor. In the case of ligand aurintricarboxylic acid docked with integrase with an Mg+2, the minimized binding free energy is -45.19 kJ/mol. It is found that the water molecules located in the active site are substituted by the carbonyl oxygen atoms of aurintricarboxylic acid,and the two oxygen atoms in the carboxy group of aurintricarboxylic acid can form a hexahedral ligand structure with the two oxygen atoms of Asp64 and Asp116. Thus, the complex has a much more stable structure with low energy due to a salt bond interaction between aurintricarboxylic acid and Mg+2. When the Mg+2 is lost, the configuration of integrase in the active site will be changed, which makes the binding free energy (-24.35 kJ/mol) increase distinctly. In the present study the unknown complex structure of HIV-1 integrase and its inhibitor aurintricarboxylic acid has been predicted, which may offer significant information on the drug design of the anti HIV-1 integrase based on structure.
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Prediction of the Interaction of HIV-1 Integrase and Inhibitor Aurintricarboxylic Acid Using Docking

doi: 10.1088/1674-0068/16/4/257-260

Abstract: A docking approach is proposed for the prediction of the interaction of HIV-1 integrase(IN) and inhibitor aurintricarboxylic acid. In order to clarify the function of metal ions on the binding process, we chose two kinds of integrase receptors (one with an Mg+2and another without Mg+2) and performed docking with aurintricarboxylic acid respectively. The receptor structure used for docking was made by the following processes. Because there is no report on the three-dimensional structure of IN/aurintricarboxylic acid complex, the only known crystals structure of the complex of the HIV-1 integrase core domain with an inhibitor 5CITEP(PDB code 1QS4) was referenced, and the monomer coordinate(chain A) was selected. Then, the lacked residues from number 141 to 144 were added by using Insight II. The final structure after 200 ps molecular dynamics simulation was used as the receptor structure for docking. The flexibility of the small molecule was allowed through rotating its dihedrals. The genetic algorithm was used and the empirical potential was taken as an energy score function when docking was being done. All possible conformations were searched throughout the full configuration space. The results of our study illustrate that the ion Mg+2 is important for the stability of the binding of the ligand and receptor. In the case of ligand aurintricarboxylic acid docked with integrase with an Mg+2, the minimized binding free energy is -45.19 kJ/mol. It is found that the water molecules located in the active site are substituted by the carbonyl oxygen atoms of aurintricarboxylic acid,and the two oxygen atoms in the carboxy group of aurintricarboxylic acid can form a hexahedral ligand structure with the two oxygen atoms of Asp64 and Asp116. Thus, the complex has a much more stable structure with low energy due to a salt bond interaction between aurintricarboxylic acid and Mg+2. When the Mg+2 is lost, the configuration of integrase in the active site will be changed, which makes the binding free energy (-24.35 kJ/mol) increase distinctly. In the present study the unknown complex structure of HIV-1 integrase and its inhibitor aurintricarboxylic acid has been predicted, which may offer significant information on the drug design of the anti HIV-1 integrase based on structure.

Song Wei, Chen Weizu, Zhang Xiaoyi, Wang Cunxin. Prediction of the Interaction of HIV-1 Integrase and Inhibitor Aurintricarboxylic Acid Using Docking[J]. Chinese Journal of Chemical Physics , 2003, 16(4): 257-260. doi: 10.1088/1674-0068/16/4/257-260
Citation: Song Wei, Chen Weizu, Zhang Xiaoyi, Wang Cunxin. Prediction of the Interaction of HIV-1 Integrase and Inhibitor Aurintricarboxylic Acid Using Docking[J]. Chinese Journal of Chemical Physics , 2003, 16(4): 257-260. doi: 10.1088/1674-0068/16/4/257-260

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