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

Journal of Receptor and Signal Transduction Research
Jiale PengZhili Zuo

Abstract

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 mor...Continue Reading

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Citations

Sep 29, 2020·Frontiers in Cell and Developmental Biology·Ting XinFang Hu
Nov 5, 2020·Journal of Biomolecular Structure & Dynamics·Khedidja BenarousLuciano Saso
Jan 10, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wolfgang Sippl, Fidele Ntie-Kang
May 7, 2021·Molecular and Cellular Probes·Leila Bou-SalahMohamed Yousfi

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