Homology Models of Melatonin Receptors: Challenges and Recent Advances

International Journal of Molecular Sciences

Daniele Pala²  Alessio Lodola²  Annalida Bedini¹  Gilberto Spadoni¹ 

[1] Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino “Carlo Bo”, Piazza Rinascimento 6, I-61029 Urbino, Italy; E-Mails:;Dipartimento di Farmacia, Università degli Studi di Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy; E-Mails:

关键词: melatonin receptors;    MT₁;    MT₂;    homology modeling;    structure-activity relationships;    docking;    molecular dynamics simulations;   

DOI  :  10.3390/ijms14048093

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland