Abstract: Melatonin exerts many of its actions through the activation of two G protein-coupled receptors (GPCRs), named MT1 and MT2. So far, a number of different MT1 and MT2 receptor homology models, built either from the prototypic structure of rhodopsin or from recently solved X-ray structures of druggable GPCRs, have been proposed. These receptor models differ in the binding modes hypothesized for melatonin and melatonergic ligands, with distinct patterns of ligand-receptor interactions and putative bioactive conformations of ligands. The receptor models will be described, and they will be discussed in light of the available information from mutagenesis experiments and ligand-based pharmacophore models. The ability of these ligand-receptor complexes to rationalize structure-activity relationships of known series of melatonergic compounds will be commented upon.
Keywords: melatonin receptors; MT1; MT2; homology modeling; structure-activity relationships; docking; molecular dynamics simulations
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Pala, D.; Lodola, A.; Bedini, A.; Spadoni, G.; Rivara, S. Homology Models of Melatonin Receptors: Challenges and Recent Advances. Int. J. Mol. Sci. 2013, 14, 8093-8121.
Pala D, Lodola A, Bedini A, Spadoni G, Rivara S. Homology Models of Melatonin Receptors: Challenges and Recent Advances. International Journal of Molecular Sciences. 2013; 14(4):8093-8121.
Pala, Daniele; Lodola, Alessio; Bedini, Annalida; Spadoni, Gilberto; Rivara, Silvia. 2013. "Homology Models of Melatonin Receptors: Challenges and Recent Advances." Int. J. Mol. Sci. 14, no. 4: 8093-8121.