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Virtual Screening of C. Sativa Constituents for the Identification of Selective Ligands for Cannabinoid Receptor 2
- Source :
- International Journal of Molecular Sciences, Vol 21, Iss 5308, p 5308 (2020), International Journal of Molecular Sciences, Volume 21, Issue 15
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- The selective targeting of the cannabinoid receptor 2 (CB2) is crucial for the development of peripheral system-acting cannabinoid analgesics. This work aimed at computer-assisted identification of prospective CB2-selective compounds among the constituents of Cannabis Sativa. The molecular structures and corresponding binding affinities to CB1 and CB2 receptors were collected from ChEMBL. The molecular structures of Cannabis Sativa constituents were collected from a phytochemical database. The collected records were curated and applied for the development of quantitative structure-activity relationship (QSAR) models with a machine learning approach. The validated models predicted the affinities of Cannabis Sativa constituents. Four structures of CB2 were acquired from the Protein Data Bank (PDB) and the discriminatory ability of CB2-selective ligands and two sets of decoys were tested. We succeeded in developing the QSAR model by achieving Q2 5-CV &gt<br />0.62. The QSAR models helped to identify three prospective CB2-selective molecules that are dissimilar to already tested compounds. In a complementary structure-based virtual screening study that used available PDB structures of CB2, the agonist-bound, Cryogenic Electron Microscopy structure of CB2 showed the best statistical performance in discriminating between CB2-active and non-active ligands. The same structure also performed best in discriminating between CB2-selective ligands from non-selective ligands.
- Subjects :
- 0301 basic medicine
Quantitative structure–activity relationship
Cannabinoid receptor
medicine.medical_treatment
Protein Data Bank (RCSB PDB)
Computational biology
Catalysis
Inorganic Chemistry
lcsh:Chemistry
03 medical and health sciences
0302 clinical medicine
medicine
Cannabinoid receptor type 2
Physical and Theoretical Chemistry
endocannabinoid system
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Virtual screening
Chemistry
QSAR
Organic Chemistry
General Medicine
computer.file_format
chEMBL
Protein Data Bank
Computer Science Applications
Cannabis Sativa
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
lipids (amino acids, peptides, and proteins)
Cannabinoid
computer
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 21
- Issue :
- 5308
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....b69baf0da980dbdee6b46953d75bbce6