期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

HIV-1整合酶与抑制剂金精三羧酸复合物的分子动力学模拟 被引量：1

Molecular Dynamics Simulation on the Complex of HIV-1 Integrase and the Inhibitor Aurintricarboxylic Acid
下载PDF
导出
摘要 用分子对接程序 (Autodock)将含有一个Mg2 + 的HIV 1整合酶核心区 (以下简称IN A)与抑制剂小分子金精三羧酸(简称Aurin)进行对接 ,预测其未知的复合物结构 ,然后用分子动力学 (MD)方法对IN A与Aurin的对接结果进行了 95 0ps的模拟 .MD模拟结果发现 ,IN A与Aurin形成了两个稳定的氢键 ,Mg2 + 也与Aurin上的氧原子形成了稳定的配键 ,IN A与Aurin之间的静电相互作用能和范德华相互作用能的平均值分别为 -2 0 5 8和 -162 7kJ/mol .根据MD模拟得到的IN A与Aurin相互作用后的构象变化信息 ,我们对对接复合物结构进行了修正 ,给出了更加合理和稳定的复合物预测结构 .本工作得到的HIV 1整合酶与抑制剂Aurin的结合模式信息将有助于设计和改造出效果更好的抗HIV 1整合酶的先导化合物 . Molecular dynamics simulation method was used to study the complex structure of HIV-1 integrase and its inhibitor aurintricarboxylic acid (Aurin). The HIV-1 integrase core domain (IN-A) with a Mg2+ and inhibitor Aurin molecule are docked as a complex with the program Autodock. A 950 ps molecular dynamics simulation was carried out on the complex system. The simulation shows the stability of the complex. It was found that there are two stable hydrogen bonds between IN-A and Aurin in the predicted complex structure. The Mg2+ is also chelated with an oxygen atom of Aurin. The mean electrostatic interaction and the mean van der Waals interaction between IN-A and Aurin are -205.8 and -162.7 kJ/mol, respectively. The result of our simulation and the predicted complex structure will be useful in designing anti HIV-1 integrase inhibitor.
作者 朱海梅 陈慰祖 王存新
机构地区 北京工业大学生命科学与生物工程学院
出处 《化学学报》 SCIE CAS CSCD 北大核心 2004年第8期745-749,共5页 Acta Chimica Sinica
基金 北京市自然科学基金 (Nos .5 0 32 0 0 2 5 0 4 2 0 0 3) 国家自然科学基金 (Nos .30 170 2 30 10 174 0 0 5 )资助项目
关键词 艾滋病 病毒复制 HIV-1整合酶 抑制剂 金精三羧酸复合物 分子动力学 药物设计 分子对接程序 HIV-1 integruse aurintricarboxylic acid docking melocular dynamics
分类号 TQ463 [化学工程—制药化工]
  • 相关文献

参考文献2

二级参考文献39

  • 1[1]Pommier Y, Marchand C, Neamati N. Retroviral integrase inhibit ors year 2000: update and perspectives[J]. Antiviral Res,2000,47:139-148.
  • 2[2]Esposito D, Craigie R. HIV integrase structure and function[A]. In : Skalka A M (Ed.). Advances in Virus Research[M], San Diego: Acad emic Press, 1999,Vol.52 pp:319-333.
  • 3[3]Craigie R. HIV integrase, a brief overview from chemistry to therapeu tics[J]. J Biol Chem, 2001,276(26):23213-23216.
  • 4[4]Drake R, Neamati N, Hong H, et al. Identification of a nucleotide b inding site in HIV-1 integrase[J]. Proc Natl Acad Sci USA, 1993,95:4170- 4175.
  • 5[5]Goldgur Y, Craigie R, Cohen C H, et al. Structure of the HIV-integra se catalytic domain complexed with an inhibitor:a platform for antiviral drug de sign[J]. Proc Natl Acad Sci USA, 1999,96:13040-13043.
  • 6[6]Jing N, Marchad C, Liu J, et al. Mechanism of inhibition of HIV-1 in teg rase by G-tetra forming oligonucleotides[J]. J Biol Chem, 2000,275:21460 -21467.
  • 7[7]Caumont A, Jamieson G, Soultrait V R, et al. High affinityinteraction of HIV-1 integrase with specific and non-specific single-stranded short oli gonucleotides[J]. FEBS Lett, 1999,455:154-158.
  • 8[8]Daria J, Hazuda P F, Witmer M, et al. Inhibitors of strand transfer t hat prevent integration and inhibit HIV-1 replication in cells[J]. Science, 2000,287:646-650.
  • 9[9]Goldgur Y, Craigie R, Cohen G H, et al. Structure of the HIV-integr ase catalytic domain complexed with an inhibitorf a pIatform for antiviral drug design[J]. Proc Natl Acad Sci USA,1999,96:13040-13043.
  • 10[10]Neamati N, Turpin J A, Winslow H E, et al. Thiazolothiazepine inhibitors of HIV-1 integrase[J]. J Med Chem, 1999,42:3334-3341.

共引文献11

同被引文献23

  • 1马晓慧,陈慰祖,王存新.用从头药物设计方法合理设计HIV-1整合酶抑制剂[J].军事医学科学院院刊,2005,29(4):355-358. 被引量：1
  • 2Lepesheva G, Hargrove T, Kleshchenko Y, et al. CYP51: A major drug target in the cytochrome P450 superfamily. Lipids, 2008, 43(12): 1117-1125.
  • 3Lamb D C, Kelly D E, Venkateswarlu K, et ol. Generation of a complete, soluble, and catalytically active sterol 14 alpha- demethylase-reductase complex. Biochemistry, 1999, 38 (27): 8733-8738.
  • 4Sheng C, Miao Z, Ji H, et al. Three-dimensional model of lanosterol 14 alpha-demethylase from cryptococcus neoformans: active-site characterization and insights into azole binding. Antimicrob Agents Chemother, 2009, 53(8): 3487-3495.
  • 5Zhao L, Liu D L, Zhang Q Y, et al. Expression and homology modeling of sterol 14 alpha-demethylase from Penicillium digitatum. FEMS Microbiol Lett, 2007, 277(1): 37-43.
  • 6Lepesheva G I, Park H W, Hargrove T Y, et al. Crystal structures of Trypanosoma brucei sterol 14alpha-demethylase and implicationsfor selective treatment of human infections. J Biol Chem, 2010, 285(3): 1773-1780.
  • 7Strushkevich N, Usanov S A, Park H W. Structural basis of human CYP51 inhibition by antifungal azoles. J Mol Biol, 2010, 397(4): 1067-1078.
  • 8Thompson J D, Higgins D G, Gibson T J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research, 1994, 22(22): 4673-4680.
  • 9Eswar N, Webb B, Marti-renom M A, et al. Comparative protein structure modeling using MODELLER. Curr Protoc Protein Sci, 2007, 2(12): 15-32.
  • 10Lindahl E, Hess B, Vander S D. GROMACS 3.0: a package for molecular simulation and trajectory analysis. J Mol Model, 2001, 7(8): 306-317.

引证文献1

二级引证文献3

化学学报
2004年 第8期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部