ArticleJournal of the American Chemical Society2008
Atomistic insights into rhodopsin activation from a dynamic model.
Article in Journal of the American Chemical Society, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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
14 citing papers in PubMed, 34 citations in OpenAlex.
- Simulating the distance distribution between spin-labels attached to proteins.The journal of physical chemistry. B · 2015Article
- Differential light-induced responses in sectorial inherited retinal degeneration.The Journal of biological chemistry · 2014Article
- Novel insights on thyroid-stimulating hormone receptor signal transduction.Endocrine reviews · 2013Review
- Deconstructing activation events in rhodopsin.Journal of the American Chemical Society · 2013Article
- Structural refinement from restrained-ensemble simulations based on EPR/DEER data: application to T4 lysozyme.The journal of physical chemistry. B · 2013Article
- Activation mechanism of the β2-adrenergic receptor.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Showcasing modern molecular dynamics simulations of membrane proteins through G protein-coupled receptors.Current opinion in structural biology · 2011Review
- From molecular details of the interplay between transmembrane helices of the thyrotropin receptor to general aspects of signal transduction in family a G-protein-coupled receptors (GPCRs).The Journal of biological chemistry · 2011Article
- Docking-based virtual screening for ligands of G protein-coupled receptors: not only crystal structures but also in silico models.Journal of molecular graphics & modelling · 2011Article
- Light activation of rhodopsin: insights from molecular dynamics simulations guided by solid-state NMR distance restraints.Journal of molecular biology · 2010Article
- Article
- A Comparison of Three Perturbation Molecular Dynamics Methods for Modeling Conformational Transitions.Journal of chemical theory and computation · 2009Article
- Identification of two distinct inactive conformations of the beta2-adrenergic receptor reconciles structural and biochemical observations.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Unraveling the structure and function of G protein-coupled receptors through NMR spectroscopy.Current pharmaceutical design · 2009Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Rhodopsin, the light sensitive receptor responsible for blue-green vision, serves as a prototypical G protein-coupled receptor (GPCR). Upon light absorption, it undergoes a series of conformational changes that lead to the active form, metarhodopsin II (META II), initiating a signaling cascade through binding to the G protein transducin (G(t)). Here, we first develop a structural model of META II by applying experimental distance restraints to the structure of lumi-rhodopsin (LUMI), an earlier intermediate. The restraints are imposed by using a combination of biased molecular dynamics simulations and perturbations to an elastic network model. We characterize the motions of the transmembrane helices in the LUMI-to-META II transition and the rearrangement of interhelical hydrogen bonds. We then simulate rhodopsin activation in a dynamic model to study the path leading from LUMI to our META II model for wild-type rhodopsin and a series of mutants. The simulations show a strong correlation between the transition dynamics and the pharmacological phenotypes of the mutants. These results help identify the molecular mechanisms of activation in both wild type and mutant rhodopsin. While static models can provide insights into the mechanisms of ligand recognition and predict ligand affinity, a dynamic model of activation could be applicable to study the pharmacology of other GPCRs and their ligands, offering a key to predictions of basal activity and ligand efficacy.
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.