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Endogenous opioids produce the same effects as the chemicals known as classic alkaloid opiates, which include morphine and heroin. Endogenous opioid peptides function both as hormones and as neuromodulators. The aim of the present study was to analyze the results of docking of ligands with MOR to identify the key elements required for selectivity. Many of the ligands have been synthesized and biologically tested by our colleagues. The other part is compounds known in the literature. The analysis of the obtained ligand-receptor complexes makes it possible to determine the key structural elements associated with the manifestation of specificity with respect to the receptor. These results will assist in the design of new compounds with potential MOR agonistic or antagonistic effects. In order to be active and effective, a ligand must have certain properties. First, it must be stable in a biological environment so that it can reach the place where it will manifest its action. Second, be of a suitable structure to allow it to reach and interact with the receptor's binding site. Third, upon binding, the resulting ligand-receptor complex should be stable, i.e. its energy to be small. Fourth, the ligand induces the appropriate conformations in the receptor molecule upon interaction, i.e. to bind to precisely defined amino acid residues. Therefore, the present study aims to analyze the docking results of dalargine derivatives with MOR and determine the necessary conditions for the manifestation of the biological effect. [ABSTRACT FROM AUTHOR]

The endocannabinoid system consists of endocannabinoids, cannabinoid receptors and enzymes that synthesise and degrade the endocannabinoids. The cannabinoid receptors (CBR) are an important class of receptors participating in various physiological processes. Many of their effects are mediated by two G protein-coupled receptors (GPCRs), (CB1) and (CB2), although additional receptors may be involved. The purpose of this paper is to present a computer modelling of the CBR and several known cannabinoid ligands aiming to determine the structure-activity relationship by using molecular docking with GOLD software. Four scoring functions provided by GOLD are used for molecular docking of the models of CBR1, its crystal structure and the known cannabinoid ligands. Significant correlations between the biological activity of the ligands and the ChemScore optimization function are established. The results obtained could be further used for in silico experiments of the interaction between CBR and cannabinoid ligands. [ABSTRACT FROM AUTHOR]

Cannabinoid receptor type 2 (CB2) is a member of the G protein-coupled receptor superfamily. CB2 plays an important role in regulating receptor desensitization and internalization. It has protective effects in chronic degenerative diseases. 3D homology models of different templates in absence of CB2 receptor crystal structures are reported in the literature, but their wide use is limited. The aims of the present study are: 1) to choose among the published crystallographic structures templates for CB2 receptor homology modelling and to evaluate them with different computational tools; 2) to investigate the interaction between the developed model of CB2 and several known cannabinoid ligands aiming to determine the structure-activity relationship by molecular docking with GOLD 5.2 software. A significant correlation between the docking results (ChemScore function) and the ligands biological activity is found. The results obtained could be further used in silico experiments of the cannabinoid receptor-ligand interactions. [ABSTRACT FROM AUTHOR]

Mu-opioid receptor (MOR) is an attractive target for in silico docking experiments. Many potent analgesics currently in use act through the MOR. The main objective of the present work was to find the polynomial function for modelling of the structure-activity relationship of a series of MOR analogues and the results of the molecular docking with MOR (PDBid:4dkl). The relationship of the biological activity of the ligands with the ChemScore function and with the total energy (MolDock function) was modelled with first- to thirddegree polynomials and surface fitted method, assessed by least squares method. The finding, established in the paper, suggests that the third order polynomial could be successfully used for modelling of the relationship between the biological effect of the MOR analogues and results from docking procedure. Analysis and comparison of the data from in vitro tests and docking studies could help to understand better the relationship between in vitro biological effects and docking studies and to answer whether the models of the biological macromolecules (in our case MOR) correspond to the real 3D structure. [ABSTRACT FROM AUTHOR]