Pharmacophore modeling, molecular docking and molecular dynamics studies on natural products database to discover novel skeleton as non-puricie xanthine oxidase inhibitors

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	Pharmacophore modeling, molecular docking and molecular dynamics studies on natural products database to discover novel skeleton as non-puricie xanthine oxidase inhibitors
	Peng, Jiale; Li, Yaping; Zhou, Yeheng; Zhang, Li; Liu, Xingyong; Zuo, Zhili
	2018
发表期刊	JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
ISSN	1079-9893
卷号	38 期号:3 页码:246-255
摘要	Gout is a common inflammatory arthritis caused by the deposition of urate crystals within joints. It is increasingly in prevalence during the past few decades as shown by the epidemiological survey results. Xanthine oxidase (XO) is a key enzyme to transfer hypoxanthine and xanthine to uric acid, whose overproduction leads to gout. Therefore, inhibiting the activity of xanthine oxidase is an important way to reduce the production of urate. In the study, in order to identify the potential natural products targeting XO, pharmacophore modeling was employed to filter databases. Here, two methods, pharmacophore based on ligand and pharmacophore based on receptor-ligand, were constructed by Discovery Studio. Then GOLD was used to refine the potential compounds with higher fitness scores. Finally, molecular docking and dynamics simulations were employed to analyze the interactions between compounds and protein. The best hypothesis was set as a 3D query to screen database, returning 785 and 297 compounds respectively. A merged set of the above 1082 molecules was subjected to molecular docking, which returned 144 hits with high-fitness scores. These molecules were clustered in four main kinds depending on different backbones. What is more, molecular docking showed that the representative compounds established key interactions with the amino acid residues in the protein, and the RMSD and RMSF of molecular dynamics results showed that these compounds can stabilize the protein. The information represented in the study confirmed previous reports. And it may assist to discover and design new backbones as potential XO inhibitors based on natural products.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/64761
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Peng, Jiale,Li, Yaping,Zhou, Yeheng,et al. Pharmacophore modeling, molecular docking and molecular dynamics studies on natural products database to discover novel skeleton as non-puricie xanthine oxidase inhibitors[J]. JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION,2018,38(3):246-255.
APA	Peng, Jiale,Li, Yaping,Zhou, Yeheng,Zhang, Li,Liu, Xingyong,&Zuo, Zhili.(2018).Pharmacophore modeling, molecular docking and molecular dynamics studies on natural products database to discover novel skeleton as non-puricie xanthine oxidase inhibitors.JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION,38(3),246-255.
MLA	Peng, Jiale,et al."Pharmacophore modeling, molecular docking and molecular dynamics studies on natural products database to discover novel skeleton as non-puricie xanthine oxidase inhibitors".JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION 38.3(2018):246-255.