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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]

Blood pressure and fluid balance are regulated hormonally by renin-angiotensin system (RAS). Influence on this system could be achieved by different compounds that act as angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers and renin inhibitors. The purpose of the present study is to predict the structures of the potent ACE inhibitors on the base of His-Leu peptide structural element of angiotensine I using computational methods. Different modifications were made in the structure of this dipeptide and the energy of binding with the enzyme were calculated. The docking results were analyzed and it was found that along with the important amino acid residue of the receptor molecule Arg167, the Tyr residues (35, 87, 88 and 92) as well as Cys180 are extremely important for the strong binding to the receptor and, accordingly, the manifestation of antagonistic action by the analogues. To block the receptor, the ligand molecule must have an intact terminal carboxyl group and an imidazole nucleus to participate in appropriate interactions. The inclusion of functional groups in the side chains of the amino acid residues of the dipeptide create an additional site for binding to the receptor. With the help of docking, the ligand molecule can be optimized, and this process is fast, saving the synthesis of many compounds and their biological testing. And finally, the most potent analogues will be synthesized and biologically tested. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the structure-activity relationship between cannabinoid and opioid ligands with models of cannabinoid and opioid receptors. There are differences in the mechanisms of pain control for these two types of receptors, but targeting the creation of compounds that bind to both opioid and cannabinoid receptors lead to more effective solving of this problem. This will lead to the development of new and improved strategies to prevent opiate addiction and its consequences. [ABSTRACT FROM AUTHOR]

Proctolin (RYLPT) has been the first invertebrate neuropeptide to be fully sequenced (already in 1975). Its structure is identical in both crustaceans and insects, where it has myo- and neurostimulatory actions. The Drosophila receptor has been the first invertebrate proctolin receptor to be identified. Over the years, a large number of agonists and antagonists have been synthesized to find the structure-activity relationship. Computer methods now enable the quick analyses of various analogs. The aim of the present study is to model the proctolin receptor and to perform docking with known analogues, both agonist and antagonist. The new model of a proctolin receptor is modeled and a significant correlation between the results of docking and in vitro experiments (Pearson's r = 0.8627 and P value = 0.0270) is found. The results obtained are promising and open an area of a further profound investigation aiming to optimize the receptor structure and to design new agonists and antagonists of proctolin. [ABSTRACT FROM AUTHOR]

The bioactive peptides are specific protein fragments which have a positive effect on the body functions and conditions. These peptides have a hormone- or a drug like activity and play an important role. The antihypertensive peptides are a significant group of these peptides, which are used as angiotensin-converting enzymes inhibitors, because they are associated with the high blood pressure decrease and play an important role in cardiovascular diseases. Angiotensin-I Converting Enzyme (ACE) is one of the major components of the so-called Renin-Angiotensin System (RAS). Renin is responsible for the release of Angiotensin I (AI) in blood because of its catalytic action on angiotensinogen. The role of ACE connected with the inhibition of ACE enzymatic activity against AI is considered one of the major challenges in case of a hypertensive disease and a congestive heart failure. The present investigation is focused on the synthesis of His-Leu and Val-Trp peptide analogues using well know procedures. The intermediates and the dipeptide analogues are characterized by TLC and spectral methods. The computer modeling and the docking studies are performed to determine the structure-activity relationship and to synthesize new potential ACE inhibitors. [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]

The somatostatin receptors (SSTRs) are a very important class of receptors that attract the attention of a great number of scientists. The development of effective and selective ligands of each somatostatin receptor type is a time consuming process, which involves the knowledge and the skills of different researchers: chemists, biologists, medics, pharmacologists, etc. A large number of compounds is synthesized, characterized and biologically tested, but just some of them have the desired efficacy and selectivity to a respective somatostatin receptor type. The aims of the present study are: (1) to choose templates, among the recently published crystallographic structures, for homology modelling of all five types of SSTRs; (2) to evaluate the models by different computational tools (Procheck, MolProbity, docking). The structures of SSTRs are modelled using the Chimera software and their characteristics are evaluated on the ground of different methods. The best models are used for docking with recently synthesized and biologically tested somatostatin analogues selective to certain SSTR. The data, especially from docking, shows that the newly generated model of SSTRs could be further used for in silico experiments providing a faster and a better design of selective and effective ligands of SSTRs. [ABSTRACT FROM AUTHOR]