Virtual screening using docking and molecular dynamics of cannabinoid analogs against CB1 and CB2 receptors |
| |
| Institution: | 1. Pharmacology and Therapeutic Group, Faculty of Pharmaceutical Sciences, University of Cartagena, Cartagena, Colombia;2. GINUMED, Faculty of Medicine, Rafael Nuñez University Corporation, Cartagena, Colombia;3. Faculty of Pharmaceutical Sciences, University of Cartagena, Cartagena, Colombia;1. Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, 136119, India;2. Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, 125001, India;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Egypt;2. Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Research Site Leipzig, Leipzig 04318, Germany;1. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan;2. Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, 616, Oman;3. Jamil-ur-Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan;4. Department of Chemistry, University of Karachi, Karachi, 75270, Pakistan;1. Institute of Legal Medicine, University of Frankfurt/Main, Kennedyallee 104, D-60596 Frankfurt/Main, Germany;2. Institute of Pharmaceutical Chemistry, University of Frankfurt/Main, Max-von-Laue Straße 9, D-60438 Frankfurt/Main, Germany |
| |
| Abstract: | BackgroundCannabis sativa has been attributed to different pharmacological properties. A number of secondary metabolites such as tetrahydrocannabinol (THC), cannabinol (CBD), and different analogs, with highly promising biological activity on CB1 and CB2 receptors, have been identified.MethodsThus, this study aimed was to evaluate the activity of THC, CBD, and their analogs using molecular docking and molecular dynamics simulations (MD) methods. Initially, the molecules (ligands) were selected by bioinformatics searches in databases. Subsequently, CB1 and CB2 receptors were retrieved from the protein data bank database. Afterward, each receptor and its ligands were optimized to perform molecular docking. Then, MD Simulation was performed with the most stable ligand-receptor complexes. Finally, the Molecular Mechanics-Generalized Born Surface Area (MM-PBSA) method was applied to analyze the binding free energy between ligands and cannabinoid receptors.ResultsThe results obtained showed that ligand LS-61176 presented the best affinity in the molecular docking analysis. Also, this analog could be a CB1 negative allosteric modulator like CBD and probably an agonist in CB2 like THC and CBD according to their dynamic behavior in silico. The possibility of having a THC and a CBD analog (LS-61176) as a promising molecule for experimental evaluation since it could have no central side-effects on CB1 and have effects of CB2 useful in pain, inflammation, and some immunological disorders. Docking results were validate using ROC curve for both cannabinoids receptor where AUC for CB1 receptor was 0.894±0.024, and for CB2 receptor AUC was 0.832±0032, indicating good affinity prediction. |
| |
| Keywords: | Cannabis THC CBD Molecular docking Molecular dynamics |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
