Discovery of Potential Orthosteric and Allosteric Antagonists of P2Y1R from Chinese Herbs by Molecular Simulation Methods
Joint Authors
Luo, Ganggang
Lu, Fang
Zhang, Yanling
Zhang, Xu
Chen, Yan-kun
Jiang, Lu-di
Qiao, Lian-sheng
Xiang, Yu-hong
Source
Evidence-Based Complementary and Alternative Medicine
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-08-21
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
P2Y1 receptor (P2Y1R), which belongs to G protein-coupled receptors (GPCRs), is an important target in ADP-induced platelet aggregation.
The crystal structure of P2Y1R has been solved recently, which revealed orthosteric and allosteric ligand-binding sites with the details of ligand-protein binding modes.
And it suggests that P2Y1R antagonists, which recognize two distinct sites, could potentially provide an efficacious and safe antithrombotic profile.
In present paper, 2D similarity search, pharmacophore based screening, and molecular docking were used to explore the potential natural P2Y1R antagonists.
2D similarity search was used to classify orthosteric and allosteric antagonists of P2Y1R.
Based on the result, pharmacophore models were constructed and validated by the test set.
Optimal models were selected to discover potential P2Y1R antagonists of orthosteric and allosteric sites from Traditional Chinese Medicine (TCM).
And the hits were filtered by Lipinski’s rule.
Then molecular docking was used to refine the results of pharmacophore based screening and analyze the binding mode of the hits and P2Y1R.
Finally, two orthosteric and one allosteric potential compounds were obtained, which might be used in future P2Y1R antagonists design.
This work provides a reliable guide for discovering natural P2Y1R antagonists acting on two distinct sites from TCM.
American Psychological Association (APA)
Zhang, Xu& Lu, Fang& Chen, Yan-kun& Luo, Ganggang& Jiang, Lu-di& Qiao, Lian-sheng…[et al.]. 2016. Discovery of Potential Orthosteric and Allosteric Antagonists of P2Y1R from Chinese Herbs by Molecular Simulation Methods. Evidence-Based Complementary and Alternative Medicine،Vol. 2016, no. 2016, pp.1-12.
https://search.emarefa.net/detail/BIM-1104141
Modern Language Association (MLA)
Zhang, Xu…[et al.]. Discovery of Potential Orthosteric and Allosteric Antagonists of P2Y1R from Chinese Herbs by Molecular Simulation Methods. Evidence-Based Complementary and Alternative Medicine No. 2016 (2016), pp.1-12.
https://search.emarefa.net/detail/BIM-1104141
American Medical Association (AMA)
Zhang, Xu& Lu, Fang& Chen, Yan-kun& Luo, Ganggang& Jiang, Lu-di& Qiao, Lian-sheng…[et al.]. Discovery of Potential Orthosteric and Allosteric Antagonists of P2Y1R from Chinese Herbs by Molecular Simulation Methods. Evidence-Based Complementary and Alternative Medicine. 2016. Vol. 2016, no. 2016, pp.1-12.
https://search.emarefa.net/detail/BIM-1104141
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1104141