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Insight into HIV-1 reverse transcriptase–aptamer interaction from molecular dynamics simulations

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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.

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Acknowledgments

This work was supported by the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, Faculty of Science at Kasetsart University, Kasersart University Research and Development Institute. We wish to express our gratitude for the use of high-performance computer clusters from The National Center for Genetic Engineering and Biotechnology (BIOTEC) and the National Science and Technology Development Agency (NSTDA).

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Authors and Affiliations

  1. Interdisciplinary Program in Genetic Engineering, Graduate School, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand

    Niran Aeksiri

  2. Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Chatuchak, Bangkok, Thailand

    Napat Songtawee

  3. Department of Chemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand

    M. Paul Gleeson & Supa Hannongbua

  4. Department of Biochemistry, Faculty of Science, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand

    Kiattawee Choowongkomon

  5. Center for Advanced Studies in Tropical Natural Resources, NRU-KU, Kasetsart University, Chatuchak, Bangkok, 10900, Thailand

    Kiattawee Choowongkomon

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  1. Niran Aeksiri
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  2. Napat Songtawee
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  5. Kiattawee Choowongkomon
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Correspondence to Kiattawee Choowongkomon.

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Aeksiri, N., Songtawee, N., Gleeson, M.P. et al. Insight into HIV-1 reverse transcriptase–aptamer interaction from molecular dynamics simulations. J Mol Model 20, 2380 (2014). https://doi.org/10.1007/s00894-014-2380-8

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  • DOI: https://doi.org/10.1007/s00894-014-2380-8

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