Molecular simulation study on the recognition between hydroxy isoindolin ketone derivatives and HIV-1 integrase
10.11665/j.issn.1000-5048.20160508
- VernacularTitle:羟基异吲哚酮类衍生物与HIV-1整合酶的分子模拟研究
- Author:
Wenyi DU
1
;
Jianping HU
;
Ke ZUO
;
Wei LIU
;
Li LIANG
;
Tianyang DAI
Author Information
1. 成都大学，四川抗菌素工业研究所，药食同源植物资源开发四川省高校重点实验室
- Publication Type:Journal Article
- Keywords:
hydroxy isoindol ketone derivatives;
molecular;
docking;
molecular dynamics simulation;
HIV-1 integrase;
conformation analysis
- From:
Journal of China Pharmaceutical University
2016;47(5):551-559
- CountryChina
- Language:Chinese
-
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.
