Quantum mechanics insights into melatonin and analogs binding to melatonin MT₁ and MT₂ receptors

Author(s)

Menezes, Gabriela de Lima ; Bezerra, Katyanna Sales ; Oliveira, Jonas Ivan Nobre ; Araujo, John Fontenele ; Galvao, Douglas Soares ; da Silva, Roosevelt Alves ; Saivish, Marielena Vogel ; Fulco, Umberto Laino

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 14, n. 1, p. 17-pg., 2024-05-13.

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. (AU)

• FAPESP's process: 13/08293-7 - CCES - Center for Computational Engineering and Sciences
• Grantee: Munir Salomao Skaf
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC