Docking and molecular dynamics studies toward the binding of new natural phenolic marine inhibitors and aldose reductase

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	Docking and molecular dynamics studies toward the binding of new natural phenolic marine inhibitors and aldose reductase
	Wang, Zhiguo ; Ling, Baoping ; Zhang, Rui ; Suo, Yourui ; Liu, Yongjun ; Yu, Zhangyu ; Liu, Chengbu
	2009-09-01
发表期刊	JOURNAL OF MOLECULAR GRAPHICS & MODELLING ; Wang Zhiguo,Ling Baoping,Zhang Rui,Suo Yourui,Liu Yongjun,Yu Zhangyu,Liu Chengbu.Docking and molecular dynamics studies toward the binding of new natural phenolic marine inhibitors and aldose reductase.Journal of Molecular Graphics and Modelling,2009,28:162-169
摘要	Phenolic marine natural product is a kind of new potential aldose reductase inhibitors (ARIs). In order to investigate the binding mode and inhibition mechanism, molecular docking and dynamics studies were performed to explore the interactions of six phenolic inhibitors with human aldose reductase (hALR2). Considering physiological environment, all the neutral and other two ionized states of each phenolic inhibitor were adopted in the simulation. The calculations indicate that all the inhibitors are able to form stable hydrogen bonds with the hALR2 active pocket which is mainly constructed by residues TYR48, HIS110 and TRP111, and they impose the inhibition effect by occupying the active space. In all inhibitors, only La and its two ionized derivatives La_ion1 and La_ion2, in which neither of the ortho-hydrogens of 3-hydroxyl is substituted by Br, bind with hALR2 active residues using the terminal 3-hydroxyl. While, all the other inhibitors, at least one of whose ortho-sites of 3- and 6-hydroxyls are substituted by Br substituent which take much electron-withdrawing effect and steric hindrance, bind with hALR2 through the lactone group. This means that the Br substituent can effectively regulate the binding modes of phenolic inhibitors. Although the lactone bound inhibitors have relatively high RMSD values, our dynamics study shows that both binding modes are of high stability. For each inhibitor molecule, the ionization does not change its original binding mode, but it does gradually increase the binding free energy, which reveals that besides hydrogen bonds, the electrostatic effect is also important to the inhibitor–hALR2 interaction.; Phenolic marine natural product is a kind of new potential aldose reductase inhibitors (ARIs). In order to investigate the binding mode and inhibition mechanism, molecular docking and dynamics studies were performed to explore the interactions of six phenolic inhibitors with human aldose reductase (hALR2). Considering physiological environment, all the neutral and other two ionized states of each phenolic inhibitor were adopted in the simulation. The calculations indicate that all the inhibitors are able to form stable hydrogen bonds with the hALR2 active pocket which is mainly constructed by residues TYR48, HIS110 and TRP111, and they impose the inhibition effect by occupying the active space. In all inhibitors, only La and its two ionized derivatives La_ion1 and La_ion2, in which neither of the ortho-hydrogens of 3-hydroxyl is substituted by Br, bind with hALR2 active residues using the terminal 3-hydroxyl. While, all the other inhibitors, at least one of whose ortho-sites of 3- and 6-hydroxyls are substituted by Br substituent which take much electron-withdrawing effect and steric hindrance, bind with hALR2 through the lactone group. This means that the Br substituent can effectively regulate the binding modes of phenolic inhibitors. Although the lactone bound inhibitors have relatively high RMSD values, our dynamics study shows that both binding modes are of high stability. For each inhibitor molecule, the ionization does not change its original binding mode, but it does gradually increase the binding free energy, which reveals that besides hydrogen bonds, the electrostatic effect is also important to the inhibitor-hALR2 interaction. (C) 2009 Elsevier Inc. All rights reserved.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/45841
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 studies toward the binding of new natural phenolic marine inhibitors and aldose reductase[J]. JOURNAL OF MOLECULAR GRAPHICS & MODELLING, Wang Zhiguo,Ling Baoping,Zhang Rui,Suo Yourui,Liu Yongjun,Yu Zhangyu,Liu Chengbu.Docking and molecular dynamics studies toward the binding of new natural phenolic marine inhibitors and aldose reductase.Journal of Molecular Graphics and Modelling,2009,28:162-169,2009.
APA	Wang, Zhiguo.,Ling, Baoping.,Zhang, Rui.,Suo, Yourui.,Liu, Yongjun.,...&Liu, Chengbu.(2009).Docking and molecular dynamics studies toward the binding of new natural phenolic marine inhibitors and aldose reductase.JOURNAL OF MOLECULAR GRAPHICS & MODELLING.
MLA	Wang, Zhiguo,et al."Docking and molecular dynamics studies toward the binding of new natural phenolic marine inhibitors and aldose reductase".JOURNAL OF MOLECULAR GRAPHICS & MODELLING (2009).