Insight into HIV-1 reverse transcriptase-aptamer interaction from molecular dynamics simulations
Insight into HIV-1 reverse transcriptase-aptamer interaction from molecular dynamics simulations
复制标题
DOI：
10.1007/s00894-014-2380-8
复制
发表时间：
2014-08-01
影响因子：
2.2
通讯作者：
Choowongkomon, Kiattawee
中科院分区：
文献类型：
--
作者：
Aeksiri, Niran;Songtawee, Napat;Choowongkomon, Kiattawee
人类免疫缺陷病毒1逆转录酶（HIV-1 RT）被认为是抗病毒药物治疗的关键靶点之一。适体作为潜在的HIV-1逆转录酶抑制剂的出现引起了科学界的关注，因为这些大分子可以在微摩尔至皮摩尔浓度之间有效抑制HIV-1逆转录酶。然而，目前尚不清楚适体如何与 HIV-1 RT 相互作用。我们进行了分子动力学 (MD) 研究，以便深入了解 HIV-1 RT 在与适体或 DNA 底物形成复合物时的构象动力学。因此，我们采用了三种不同的模型：apo HIV-1 RT、结合 RNA 适体的 HIV-1 RT 和结合 DNA 底物的 HIV-1 RT。结果表明，带有适体的HIV-1 RT复合物比带有DNA底物的HIV-1 RT复合物更稳定。研究发现，适体在核酸底物结合位点处以手指和拇指闭合构象与 HIV-1 RT 相互作用。我们鉴定了 HIV-1 RT 适体复合物中的关键残基，以帮助设计、开发和测试基于未来疗法的新适体。
Human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT) is considered to be one of the key targets for antiviral drug therapy. The emergence of the aptamers as potential inhibitors against HIV-1 reverse transcriptase has attracted the attention of the scientific community because these macromolecules can effectively inhibit HIV-1 RT with between micromolar to picomolar concentrations. However, it is not clear how aptamers interact with HIV-1 RT. We have undertaken a molecular dynamics (MD) study in order to gain a keen insight into the conformational dynamics of HIV-1 RT on the formation of a complex with an aptamer or DNA substrate. We have therefore employed three separate models: apo HIV-1 RT, HIV-1 RT with a bound RNA aptamer, and HIV-1 RT with a bound DNA substrate. The results show that HIV-1 RT complex with an aptamer was more stable than that with DNA substrate. It was found that the aptamer interacted with HIV-1 RT in a fingers-and-thumb-closed conformation, at the bound at the nucleic acid substrate binding site. We identified key residues within the HIV-1 RT-aptamer complex in order to help design, develop, and test a new aptamer based on therapies in the future.