Computational systems pharmacology analysis of cannabidiol

a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation

Yue min Bian, Xi bing He, Yan kang Jing, Li rong Wang, Jun mei Wang, Xiang Qun Xie

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

With treatment benefits in both the central nervous system and the peripheral system, the medical use of cannabidiol (CBD) has gained increasing popularity. Given that the therapeutic mechanisms of CBD are still vague, the systematic identification of its potential targets, signaling pathways, and their associations with corresponding diseases is of great interest for researchers. In the present work, chemogenomics-knowledgebase systems pharmacology analysis was applied for systematic network studies to generate CBD-target, target-pathway, and target-disease networks by combining both the results from the in silico analysis and the reported experimental validations. Based on the network analysis, three human neuro-related rhodopsin-like GPCRs, i.e., 5-hydroxytryptamine receptor 1 A (5HT1A), delta-type opioid receptor (OPRD) and G protein-coupled receptor 55 (GPR55), were selected for close evaluation. Integrated computational methodologies, including homology modeling, molecular docking, and molecular dynamics simulation, were used to evaluate the protein-CBD binding modes. A CBD-preferred pocket consisting of a hydrophobic cavity and backbone hinges was proposed and tested for CBD-class A GPCR binding. Finally, the neurophysiological effects of CBD were illustrated at the molecular level, and dopamine receptor 3 (DRD3) was further predicted to be an active target for CBD.

Original languageEnglish (US)
JournalActa Pharmacologica Sinica
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Cannabidiol
Knowledge Bases
Computer Simulation
Pharmacology
delta Opioid Receptor
Rhodopsin
Serotonin Receptors
Dopamine Receptors
Molecular Dynamics Simulation
G-Protein-Coupled Receptors
Protein Binding
Central Nervous System
Research Personnel

Keywords

  • 5HT
  • cannabidiol (CBD)
  • cannabinoid
  • D
  • homology modeling
  • molecular docking
  • molecular dynamics simulation
  • systems pharmacology

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Computational systems pharmacology analysis of cannabidiol : a combination of chemogenomics-knowledgebase network analysis and integrated in silico modeling and simulation. / Bian, Yue min; He, Xi bing; Jing, Yan kang; Wang, Li rong; Wang, Jun mei; Xie, Xiang Qun.

In: Acta Pharmacologica Sinica, 01.01.2018.

Research output: Contribution to journalArticle

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