ArticleBiochemistry2013
Simulations of biased agonists in the β(2) adrenergic receptor with accelerated molecular dynamics.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Agonist-specific conformational dynamics at the βBritish journal of pharmacology · 2026Article
- Cancer Immunotherapy via Disruption of Integrin αvβ3 and CD47 Costabilization on Cancer Cell Surface.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches.Molecules (Basel, Switzerland) · 2025Review
- Early Events in βThe Journal of membrane biology · 2024Article
- Coevolution-Driven Method for Efficiently Simulating Conformational Changes in Proteins Reveals Molecular Details of Ligand Effects in the β2AR Receptor.The journal of physical chemistry. B · 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
- Elucidation of a dynamic interplay between a beta-2 adrenergic receptor, its agonist, and stimulatory G protein.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mechanistic insight into the impact of a bivalent ligand on the structure and dynamics of a GPCR oligomer.Computational and structural biotechnology journal · 2022Article
- Article
- Deciphering collaborative sidechain motions in proteins during molecular dynamics simulations.Scientific reports · 2020Article
- Energy Landscapes Reveal Agonist Control of G Protein-Coupled Receptor Activation via Microswitches.Biochemistry · 2020Article
- Quantum Mechanical and Molecular Mechanics Modeling of Membrane-Embedded Rhodopsins.The Journal of membrane biology · 2019Review
- Cell-based assays and molecular dynamics analysis of a boron-containing agonist with different profiles of binding to human and guinea pig beta2 adrenoceptors.European biophysics journal : EBJ · 2019Article
- Structural insights into positive and negative allosteric regulation of a G protein-coupled receptor through protein-lipid interactions.Scientific reports · 2018Article
- Evaluation of variability in high-resolution protein structures by global distance scoring.Heliyon · 2018Article
- Structural Features and Ligand Selectivity for 10 Intermediates in the Activation Process of βACS omega · 2017Article
- Improving virtual screening of G protein-coupled receptors via ligand-directed modeling.PLoS computational biology · 2017Article
- Identification of a Different Agonist-Binding Site and Activation Mechanism of the Human P2YScientific reports · 2017Article
- Activation-Induced Conformational Changes of Dopamine D3 Receptor Promote the Formation of the Internal Water Channel.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The biased agonism of the G protein-coupled receptors (GPCRs), where in addition to a traditional G protein-signaling pathway a GPCR promotes intracellular signals though β-arrestin, is a novel paradigm in pharmacology. Biochemical and biophysical studies have suggested that a GPCR forms a distinct ensemble of conformations signaling through the G protein and β-arrestin. Here we report on the dynamics of the β2 adrenergic receptor bound to the β-arrestin and G protein-biased agonists and the empty receptor to further characterize the receptor conformational changes caused by biased agonists. We use conventional and accelerated molecular dynamics (aMD) simulations to explore the conformational transitions of the GPCR from the active state to the inactive state. We found that aMD simulations enable monitoring of the transition within the nanosecond time scale while capturing the known microscopic characteristics of the inactive states, such as the ionic lock, the inward position of F6.44, and water clusters. Distinct conformational states are shown to be stabilized by each biased agonist. In particular, in simulations of the receptor with the β-arrestin-biased agonist N-cyclopentylbutanepherine, we observe a different pattern of motions in helix 7 when compared to simulations with the G protein-biased agonist salbutamol that involves perturbations of the network of interactions within the NPxxY motif. Understanding the network of interactions induced by biased ligands and the subsequent receptor conformational shifts will lead to development of more efficient drugs.
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Registered trials
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.