title: Insight into HIV-1 reverse transcriptase-aptamer interaction from molecular dynamics simulations.
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.
authors: Interdisciplinary Program in Genetic Engineering, Graduate School, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand.
authors: Niran
authors: N
authors: Aeksiri
authors: Napat
authors: N
authors: Songtawee
authors: M Paul
authors: MP
authors: Gleeson
authors: Supa
authors: S
authors: Hannongbua
authors: Kiattawee
authors: K
authors: Choowongkomon
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D025341:Principal Component Analysis; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D052157:Aptamers, Nucleotide; D004247:DNA; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase