Knowledge Management System of Northwest Institute of Plateau Biology, CAS
| Docking and molecular dynamics study on the inhibitory activity of coumarins on aldose reductase | |
| Wang, Zhiguo1; Ling, Baoping2; Zhang, Rui1; Liu, Yongjun1,2 | |
| 2008-08-14 | |
| 发表期刊 | JOURNAL OF PHYSICAL CHEMISTRY B
 |
| 卷号 | 112期号:32页码:10033-10040 |
| 文章类型 | Article |
| 摘要 | In order to explore the inhibitory mechanism of coumarins toward aldose reductase (ALR2), AutoDock and Gromacs software were used for docking and molecular dynamics studies on 14 coumarins (CM) and ALR2 protease. The docking results indicate that residues TYR48, HIS110, and TRP111 construct the active pocket of ALR2 and, besides van der Waals and hydrophobic interaction, CM mainly interact with ALR2 by forming hydrogen bonds to cause inhibitory behavior. Except for CM1, all the other coumarins take the lactone part as acceptor to build up the hydrogen bond network with active-pocket residues. Unlike CM3, which has two comparable binding modes with ALR2, most coumarins only have one dominant orientation in their binding sites. The molecular dynamics calculation, based on the docking results, implies that the orientations of CM in the active pocket show different stabilities. Orientation of CM1 and CM3a take an unstable binding mode with ALR2; their conformations and RMSDs relative to ALR2 change a lot with the dynamic process. While the remaining CM are always hydrogen-bonded with residues TYR48 and HIS110 through the carbonyl O atom of the lactone group during the whole process, they retain the original binding mode and gradually reach dynamic equilibrium.; In order to explore the inhibitory mechanism of coumarins toward aldose reductase (ALR2), AutoDock and Gromacs software were used for docking and molecular dynamics studies on 14 coumarins (CM) and ALR2 protease. The docking results indicate that residues TYR48, HIS110, and TRP111 construct the active pocket of ALR2 and, besides van der Waals and hydrophobic interaction, CM mainly interact with ALR2 by forming hydrogen bonds to cause inhibitory behavior. Except for CM1, all the other coumarins take the lactone part as acceptor to build up the hydrogen bond network with active-pocket residues. Unlike CM3, which has two comparable binding modes with ALR2, most coumarins only have one dominant orientation in their binding sites. The molecular dynamics calculation, based on the docking results, implies that the orientations of CM in the active pocket show different stabilities. Orientation of CM1 and CM3a take an unstable binding mode with ALR2; their conformations and RMSDs relative to ALR2 change a lot with the dynamic process. While the remaining CM are always hydrogen-bonded with residues TYR48 and HIS110 through the carbonyl O atom of the lactone group during the whole process, they retain the original binding mode and gradually reach dynamic equilibrium. |
| 关键词 | Diabetic Complications |
| WOS标题词 | Science & Technology ; Physical Sciences |
| 学科领域 | 生物科学 |
| 关键词[WOS] | DIABETIC COMPLICATIONS ; FLAVONOID DERIVATIVES ; RAT ; DECURSIN ; SERIES ; ACID |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS研究方向 | Chemistry |
| WOS类目 | Chemistry, Physical |
| WOS记录号 | WOS:000258290000057 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://210.75.249.4/handle/363003/1199 |
| 专题 | 中国科学院西北高原生物研究所 |
| 作者单位 | 1.Chinese Acad Sci, NW Inst Plateau Biol, Xining 810001, Qinghai, Peoples R China 2.Shandong Univ, Sch Chem & Chem Engn, Jinan 250100, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Zhiguo,Ling, Baoping,Zhang, Rui,et al. Docking and molecular dynamics study on the inhibitory activity of coumarins on aldose reductase[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2008,112(32):10033-10040. |
| APA | Wang, Zhiguo,Ling, Baoping,Zhang, Rui,&Liu, Yongjun.(2008).Docking and molecular dynamics study on the inhibitory activity of coumarins on aldose reductase.JOURNAL OF PHYSICAL CHEMISTRY B,112(32),10033-10040. |
| MLA | Wang, Zhiguo,et al."Docking and molecular dynamics study on the inhibitory activity of coumarins on aldose reductase".JOURNAL OF PHYSICAL CHEMISTRY B 112.32(2008):10033-10040. |
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