ArticleBiochemistry2013
Toward an understanding of agonist binding to human Orexin-1 and Orexin-2 receptors with G-protein-coupled receptor modeling and site-directed mutagenesis.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Molecular Dynamics (MD) Simulation of GPR87-LPA Binding: Therapeutic Implications for Targeted Cancer Treatment.Anti-cancer agents in medicinal chemistry · 2025Article
- Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation.British journal of pharmacology · 2024Review
- In vivo photocontrol of orexin receptors with a nanomolar light-regulated analogue of orexin-B.Cellular and molecular life sciences : CMLS · 2024Article
- Synthesis of Pyrrolo[3,4-Pharmaceuticals (Basel, Switzerland) · 2023Article
- Identification of a β-arrestin-biased negative allosteric modulator for the βProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Correlated evolution of social organization and lifespan in mammals.Nature communications · 2023Article
- Characteristic structural difference between inactive and active states of orexin 2 receptor determined using molecular dynamics simulations.Biophysical reviews · 2022Review
- The Orexin receptors: Structural and anti-tumoral properties.Frontiers in endocrinology · 2022Review
- Structures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation.Nature communications · 2021Article
- Hypocretin (Orexin) Replacement Therapies.Medicine in drug discovery · 2020Article
- Understanding Peptide Binding in Class A G Protein-Coupled Receptors.Molecular pharmacology · 2019Review
- Determinants of Orexin Receptor Binding and Activation-A Molecular Dynamics Study.The journal of physical chemistry. B · 2019Article
- Investigation of New Orexin 2 Receptor Modulators UsingMolecules (Basel, Switzerland) · 2018Article
- In-silico guided discovery of novel CCR9 antagonists.Journal of computer-aided molecular design · 2018Article
- Ligand binding modes from low resolution GPCR models and mutagenesis: chicken bitter taste receptor as a test-case.Scientific reports · 2017Article
- Using the fragment molecular orbital method to investigate agonist-orexin-2 receptor interactions.Biochemical Society transactions · 2016Review
- Crucial role of the orexin-B C-terminus in the induction of OX1 receptor-mediated apoptosis: analysis by alanine scanning, molecular modelling and site-directed mutagenesis.British journal of pharmacology · 2015Article
- GPCR structure, function, drug discovery and crystallography: report from Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1-2 September 2014.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Modeling of the OX1R-orexin-A complex suggests two alternative binding modes.BMC structural biology · 2015Article
- What can we learn from molecular dynamics simulations for GPCR drug design?Computational and structural biotechnology journal · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The class A G-protein-coupled receptors (GPCRs) Orexin-1 (OX1) and Orexin-2 (OX2) are located predominantly in the brain and are linked to a range of different physiological functions, including the control of feeding, energy metabolism, modulation of neuro-endocrine function, and regulation of the sleep-wake cycle. The natural agonists for OX1 and OX2 are two neuropeptides, Orexin-A and Orexin-B, which have activity at both receptors. Site-directed mutagenesis (SDM) has been reported on both the receptors and the peptides and has provided important insight into key features responsible for agonist activity. However, the structural interpretation of how these data are linked together is still lacking. In this work, we produced and used SDM data, homology modeling followed by MD simulation, and ensemble-flexible docking to generate binding poses of the Orexin peptides in the OX receptors to rationalize the SDM data. We also developed a protein pairwise similarity comparing method (ProS) and a GPCR-likeness assessment score (GLAS) to explore the structural data generated within a molecular dynamics simulation and to help distinguish between different GPCR substates. The results demonstrate how these newly developed methods of structural assessment for GPCRs can be used to provide a working model of neuropeptide-Orexin receptor interaction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.