Structural and Energetic Analysis on the Complexes of Clinically Isolated Subtype C HIV-1 Proteases and Approved Inhibitors by Molecular Dynamics Simulation
Structural and Energetic Analysis on the Complexes of Clinically Isolated Subtype C HIV-1 Proteases and Approved Inhibitors by Molecular Dynamics Simulation
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DOI：
10.1021/jp908314f
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发表时间：
2010-01-14
影响因子：
3.3
通讯作者：
Hoshino, Tyuji
中科院分区：
文献类型：
--
作者：
Matsuyama, Shou;Aydan, Ay;Hoshino, Tyuji
HIV-1具有很大的遗传多样性。亚型13 HIV-1在发达国家的患者中很常见。与此相反，在发展中国家，感染非B亚型病毒，特别是C亚型HIV-1的患者人数不断增加。非B亚型HIV-1中的突变或多态性如何影响已批准的抑制剂的疗效仍有待澄清。在这项研究中，我们进行了分子动力学模拟的临床分离的C亚型HIV-1蛋白酶与三种批准的抑制剂的复合物。从结构和能量的角度，我们确定了影响油的抑制剂的结合的多态性。从HIV-1蛋白酶残基几何构型的改变，讨论了V821突变油的作用、与化学物质的关系以及C亚型HIV-1中罕见的D30 N突变的原因。
HIV-1 has a large genetic diversity. Subtype 13 HIV-1 is commonly found in patients in developed countries. In contrast, all increasing number of patients are infected with the non-B Subtype Viruses, especially with Subtype C HIV-1, in developing Countries. It remains to be clarified how mutations or polymorphisms in non-B Subtype HIV-1 influence the efficacy of the approved inhibitors. In this Study, we have performed molecular dynamics Simulations on clinically isolated subtype C HIV-1 proteases in complex with three kinds of approved inhibitors. From the structural and energetic viewpoints, we identified the polymorphisms influencing oil the binding of the inhibitors. The effect of the V821 Mutation Oil the association with chemicals and the reason for rare appearance of the D30N mutation in subtype C HIV-1 were discussed in terms of the change of geometry of the residues in HIV-1 protease.