ArticleFrontiers in pharmacology2018
Binding, Thermodynamics, and Selectivity of a Non-peptide Antagonist to the Melanocortin-4 Receptor.
Article in Frontiers in pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Capturing Peptide-GPCR Interactions and Their Dynamics.Molecules (Basel, Switzerland) · 2020Review
- Structural Complexity and Plasticity of Signaling Regulation at the Melanocortin-4 Receptor.International journal of molecular sciences · 2020Review
- A Metadynamics-Based Protocol for the Determination of GPCR-Ligand Binding Modes.International journal of molecular sciences · 2019Article
- Signal Transduction and Pathogenic Modifications at the Melanocortin-4 Receptor: A Structural Perspective.Frontiers in endocrinology · 2019Article
- Binding of histamine to the H1 receptor-a molecular dynamics study.Journal of molecular modeling · 2018Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The melanocortin-4 receptor (MC4R) is a potential drug target for treatment of obesity, anxiety, depression, and sexual dysfunction. Crystal structures for MC4R are not yet available, which has hindered successful structure-based drug design. Using microsecond-scale molecular-dynamics simulations, we have investigated selective binding of the non-peptide antagonist MCL0129 to a homology model of human MC4R (hMC4R). This approach revealed that, at the end of a multi-step binding process, MCL0129 spontaneously adopts a binding mode in which it blocks the agonistic-binding site. This binding mode was confirmed in subsequent metadynamics simulations, which gave an affinity for human hMC4R that matches the experimentally determined value. Extending our simulations of MCL0129 binding to hMC1R and hMC3R, we find that receptor subtype selectivity for hMC4R depends on few amino acids located in various structural elements of the receptor. These insights may support rational drug design targeting the melanocortin systems.
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Registered trials
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