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- Title
Insight into HIV-1 reverse transcriptase-aptamer interaction from molecular dynamics simulations.
- Authors
Choowongkomon, Kiattawee; Aeksiri, Niran; Songtawee, Napat; Gleeson, M.; Hannongbua, Supa
- Abstract
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.
- Subjects
HIV; REVERSE transcriptase; APTAMERS; MOLECULAR dynamics; ANTIVIRAL agents; DRUG therapy
- Publication
Journal of Molecular Modeling, 2014, Vol 20, Issue 8, p1
- ISSN
1610-2940
- Publication type
Article
- DOI
10.1007/s00894-014-2380-8