ArticleeLife2018
Simulation of spontaneous G protein activation reveals a new intermediate driving GDP unbinding.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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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
42 citing papers in PubMed.
- Ligand-dependent G protein dynamics underlying opioid efficacy.Nature structural & molecular biology · 2026Article
- Structural basis of stepwise G protein activation by the viral chemokine receptor US28.bioRxiv : the preprint server for biology · 2026Article
- A programmable lipid-triggered allosteric site modulates LC3 LIR receptor binding activity.Nature communications · 2026Article
- Tyrosine kinases sample unique activation ensembles.bioRxiv : the preprint server for biology · 2026Article
- Conserved residues in the Gα interface show subtype specificity in Gβγ coupling.The Journal of biological chemistry · 2026Article
- More protein-ligand data are needed for AlphaFold-like models to enable drug discovery.Current opinion in structural biology · 2026Review
- Conserved Residues in the Gα interface show subtype specificity in Gβγ coupling.bioRxiv : the preprint server for biology · 2026Article
- Article
- The G Protein Inhibitor YM-254890 is an Allosteric Glue.Journal of molecular biology · 2025Article
- Non-canonical GScientific reports · 2025Article
- Ligand-dependent G protein dynamics underlying opioid signaling efficacy.bioRxiv : the preprint server for biology · 2025Article
- Hidden GPCR structural transitions addressed by multiple walker supervised molecular dynamics (mwSuMD).eLife · 2025Article
- Prospective Evaluation of Structure-Based Simulations Reveal Their Ability to Predict the Impact of Kinase Mutations on Inhibitor Binding.The journal of physical chemistry. B · 2025Article
- Prospective evaluation of structure-based simulations reveal their ability to predict the impact of kinase mutations on inhibitor binding.bioRxiv : the preprint server for biology · 2025Article
- Minute-timescale free-energy calculations reveal a pseudo-active state in the adenosine AChem · 2024Article
- The G protein inhibitor YM-254890 is an allosteric glue.bioRxiv : the preprint server for biology · 2024Article
- Mechanistic insights into G-protein coupling with an agonist-bound G-protein-coupled receptor.Nature structural & molecular biology · 2024Article
- Ligand-induced conformational changes in the β1-adrenergic receptor revealed by hydrogen-deuterium exchange mass spectrometry.Nature communications · 2024Article
- G Protein Activation Occurs via a Largely Universal Mechanism.The journal of physical chemistry. B · 2024Article
- Folding@home: Achievements from over 20 years of citizen science herald the exascale era.Biophysical journal · 2023Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Activation of heterotrimeric G proteins is a key step in many signaling cascades. However, a complete mechanism for this process, which requires allosteric communication between binding sites that are ~30 Å apart, remains elusive. We construct an atomically detailed model of G protein activation by combining three powerful computational methods: metadynamics, Markov state models (MSMs), and CARDS analysis of correlated motions. We uncover a mechanism that is consistent with a wide variety of structural and biochemical data. Surprisingly, the rate-limiting step for GDP release correlates with tilting rather than translation of the GPCR-binding helix 5. β-Strands 1 - 3 and helix 1 emerge as hubs in the allosteric network that links conformational changes in the GPCR-binding site to disordering of the distal nucleotide-binding site and consequent GDP release. Our approach and insights provide foundations for understanding disease-implicated G protein mutants, illuminating slow events in allosteric networks, and examining unbinding processes with slow off-rates.
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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.