Quantum mechanics insights into melatonin and analogs binding to melatonin MT1 and MT2 receptors.
Sci Rep
; 14(1): 10922, 2024 05 13.
Article
em En
| MEDLINE
| ID: mdl-38740789
ABSTRACT
Melatonin receptors MT1 and MT2 are G protein-coupled receptors that mediate the effects of melatonin, a hormone involved in circadian rhythms and other physiological functions. Understanding the molecular interactions between these receptors and their ligands is crucial for developing novel therapeutic agents. In this study, we used molecular docking, molecular dynamics simulations, and quantum mechanics calculation to investigate the binding modes and affinities of three ligands melatonin (MLT), ramelteon (RMT), and 2-phenylmelatonin (2-PMT) with both receptors. Based on the results, we identified key amino acids that contributed to the receptor-ligand interactions, such as Gln181/194, Phe179/192, and Asn162/175, which are conserved in both receptors. Additionally, we described new meaningful interactions with Gly108/Gly121, Val111/Val124, and Val191/Val204. Our results provide insights into receptor-ligand recognition's structural and energetic determinants and suggest potential strategies for designing more optimized molecules. This study enhances our understanding of receptor-ligand interactions and offers implications for future drug development.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ligação Proteica
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Receptor MT1 de Melatonina
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Receptor MT2 de Melatonina
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Simulação de Dinâmica Molecular
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Simulação de Acoplamento Molecular
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Melatonina
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article