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Prediction of the Interaction of HIV-1 Integrase and Inhibitor Aurintricarboxylic Acid Using Docking
Song Wei,Chen Weizu,Zhang Xiaoyi,Wang Cunxin*
Author NameAffiliationE-mail
Song Wei College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022  
Chen Weizu College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022  
Zhang Xiaoyi College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022  
Wang Cunxin* College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100022 cxwang@bjpu.edu.cn 
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.
Key words:  HIV-1 integrase, Aurintricarboxylic acid, Binding free energy, Docking
FundProject:国家自然科学基金资助项目(29992590-2, 30170230,10174005) 和北京市自然科学基金项目(5032002) .
用分子对接方法预测HIV-1整合酶与金精三羧酸抑制剂的相互作用
宋伟,陈慰祖,张小轶,王存新*
摘要:
用分子对接方法(Docking)研究了HIV-1整合酶与其抑制剂金精三羧酸的结合过程.为弄清金属离子在结合中所起的作用,选择含有一个Mg+2或不含Mg+2的两种不同的整合酶受体分别与金精三羧酸对接.结果表明, Mg+2对稳定配体与受体的结合起了重要作用. 金精三羧酸配体与含有一个金属Mg+2的整合酶受体对接,最优结合自由能为-45.19 kJ/mol. 当Mg+2失去后,整合酶的活性中心构象将发生变化,使金精三羧酸抑制剂与整合酶的结合自由能(-24.35 kJ/mol)明显增加. 预测了未知的HIV-1整
关键词:  HIV-1整合酶  金精三羧酸  结合自由能  分子对接
DOI:10.1088/1674-0068/16/4/257-260
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