Docking and molecular dynamics study on the inhibitory activity of coumarins on aldose reductase

NWIPB OpenIR

	Docking and molecular dynamics study on the inhibitory activity of coumarins on aldose reductase
	Wang, Zhiguo ; Ling, Baoping ; Zhang, Rui ; Liu, Yongjun
	2008-08-14
发表期刊	JOURNAL OF PHYSICAL CHEMISTRY B ; Wang Zhiguo,Ling Baoping,Zhang Rui,Liu Yongjun.Docking and molecular dynamics study on the inhibitory activity of coumarins on aldose reductase.JOURNAL OF PHYSICAL CHEMISTRY B,2008,112(32):10033-10040
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.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/15035
专题	中国科学院西北高原生物研究所
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, Wang Zhiguo,Ling Baoping,Zhang Rui,Liu Yongjun.Docking and molecular dynamics study on the inhibitory activity of coumarins on aldose reductase.JOURNAL OF PHYSICAL CHEMISTRY B,2008,112(32):10033-10040,2008.
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.
MLA	Wang, Zhiguo,et al."Docking and molecular dynamics study on the inhibitory activity of coumarins on aldose reductase".JOURNAL OF PHYSICAL CHEMISTRY B (2008).