Molecular simulation study on the recognition between hydroxy isoindolin ketone derivatives and HIV-1 integrase

DU Wenyi; HU Jianping; ZUO Ke; LIU Wei; LIANG Li; DAI Tianyang

doi:10.11665/j.issn.1000-5048.20160508

Journal of China Pharmaceutical University > 2016 > 47(5): 551-559. > DOI: 10.11665/j.issn.1000-5048.20160508

DU Wenyi, HU Jianping, ZUO Ke, LIU Wei, LIANG Li, DAI Tianyang. Molecular simulation study on the recognition between hydroxy isoindolin ketone derivatives and HIV-1 integrase[J]. Journal of China Pharmaceutical University, 2016, 47(5): 551-559. DOI: 10.11665/j.issn.1000-5048.20160508

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Molecular simulation study on the recognition between hydroxy isoindolin ketone derivatives and HIV-1 integrase

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Abstract

To discuss the conformational change and the recognition mechanism of hydroxy isoindol ketone derivatives with HIV-1 integrase, fifty-eight hydroxy isoindol ketone derivatives were docked to the integrase using AutoDock program. Molecular dynamics simulation with 16 ns was carried out for the two complex modes, respectively, in which the corresponding small molecules exhibited strong inhibition ability. Main force acting on the association of small molecules with integrase was explored based on the docking complex model. After analyzing the hydrogen-bond and conformational changes, it was found that the hydrogen-bond between N155 and D64 was the key factor maintaining the DDE motif stability. Furthermore, the hydrophobic interactions between the loop region where Y143 located and the hydroxy isoindol ketone derivatives were found to play an important role for their recognition.
- hydroxy isoindol ketone derivatives,
- molecular docking,
- molecular dynamics simulation,
- HIV-1 integrase,
- conformation analysis

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Molecular simulation study on the recognition between hydroxy isoindolin ketone derivatives and HIV-1 integrase

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