ArticlePLoS computational biology2011
Predicting novel binding modes of agonists to β adrenergic receptors using all-atom molecular dynamics simulations.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Activity Map and Transition Pathways of G Protein-Coupled Receptor Revealed by Machine Learning.Journal of chemical information and modeling · 2023Article
- In Silico Analyses of a Promising Drug Candidate for the Treatment of Amyotrophic Lateral Sclerosis Targeting Superoxide Dismutase I Protein.Pharmaceutics · 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
- Screening of β1- and β2-Adrenergic Receptor Modulators through Advanced Pharmacoinformatics and Machine Learning Approaches.International journal of molecular sciences · 2021Article
- Open-Boundary Molecular Mechanics/Coarse-Grained Framework for Simulations of Low-Resolution G-Protein-Coupled Receptor-Ligand Complexes.Journal of chemical theory and computation · 2019Article
- Understanding Ligand Binding to G-Protein Coupled Receptors Using Multiscale Simulations.Frontiers in molecular biosciences · 2019Review
- In Silico Adoption of an Orphan Nuclear Receptor NR4A1.PloS one · 2015Article
- In silico study of the structurally similar ORL1 receptor agonist and antagonist pairs reveal possible mechanism of receptor activation.The protein journal · 2014Article
- Article
- Cloud-based simulations on Google Exacycle reveal ligand modulation of GPCR activation pathways.Nature chemistry · 2014Article
- Article
- Computational study on the different ligands induced conformation change of β2 adrenergic receptor-Gs protein complex.PloS one · 2013Article
- Hybrid molecular mechanics/coarse-grained simulations for structural prediction of G-protein coupled receptor/ligand complexes.PloS one · 2012Article
- Article
- The role of water in activation mechanism of human N-formyl peptide receptor 1 (FPR1) based on molecular dynamics simulations.PloS one · 2012Article
- Beyond modeling: all-atom olfactory receptor model simulations.Frontiers in genetics · 2012Article
- GPCR agonist binding revealed by modeling and crystallography.Trends in pharmacological sciences · 2011Article
- Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the binding mode of agonists to adrenergic receptors is crucial to enabling improved rational design of new therapeutic agents. However, so far the high conformational flexibility of G protein-coupled receptors has been an obstacle to obtaining structural information on agonist binding at atomic resolution. In this study, we report microsecond classical molecular dynamics simulations of β(1) and β(2) adrenergic receptors bound to the full agonist isoprenaline and in their unliganded form. These simulations show a novel agonist binding mode that differs from the one found for antagonists in the crystal structures and from the docking poses reported by in silico docking studies performed on rigid receptors. Internal water molecules contribute to the stabilization of novel interactions between ligand and receptor, both at the interface of helices V and VI with the catechol group of isoprenaline as well as at the interface of helices III and VII with the ethanolamine moiety of the ligand. Despite the fact that the characteristic N-C-C-OH motif is identical in the co-crystallized ligands and in the full agonist isoprenaline, the interaction network between this group and the anchor site formed by Asp(3.32) and Asn(7.39) is substantially different between agonists and inverse agonists/antagonists due to two water molecules that enter the cavity and contribute to the stabilization of a novel network of interactions. These new binding poses, together with observed conformational changes in the extracellular loops, suggest possible determinants of receptor specificity.
Indexed as
Identifiers
What OpenQuestion holds
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.