ArticleNature chemistry2014
Cloud-based simulations on Google Exacycle reveal ligand modulation of GPCR activation pathways.
Article in Nature chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 204 papers.
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Who cites it
204 citing papers in PubMed.
- A Minimalist Model for Navigating Conformational Landscape Uncovers the Activation Mechanism of βACS physical chemistry Au · 2026Article
- Agonist Binding Reshapes the Kinetic Landscape and Allosteric Communication of APLNR Toward Activation-Competent States.International journal of molecular sciences · 2026Article
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- An Expanded Markov State Model-Transition Path Theory Framework for Ion Conduction Reactive Pathways through Membrane Channels.The journal of physical chemistry letters · 2026Article
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- Functional Analysis of a Novel Pathogenic Glycine Amidinotransferase Mutant in Hereditary Fanconi Syndrome.Kidney medicine · 2026Article
- Sequence constraints predispose Class D GPCRs to follow an atypical activation mechanism.bioRxiv : the preprint server for biology · 2026Article
- All roads lead to Rome: Emergence of Mechanistic Divergence Shapes Activation of Class B1 G-Protein Coupled Receptors.bioRxiv : the preprint server for biology · 2026Article
- Exploring the distinct activation mechanisms of neuromedin B receptor through multiple replica molecular dynamics simulations and Markov state modeling.Acta pharmacologica Sinica · 2025Article
- Protein Structure-Function Relationship: A Kernel-PCA Approach for Reaction Coordinate Identification.Journal of chemical theory and computation · 2025Article
- Unveiling the Conformational Dynamics of the Histone Tails Using Markov State Modeling.Journal of chemical theory and computation · 2025Article
- Visualizing agonist-induced M2 receptor activation regulated by aromatic ring dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exploring transition states of protein conformational changes via out-of-distribution detection in the hyperspherical latent space.Nature communications · 2025Article
- Minute-timescale free-energy calculations reveal a pseudo-active state in the adenosine AChem · 2024Article
- Cyclopamine modulates smoothened receptor activity in a binding position dependent manner.Communications biology · 2024Article
- Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5.Nature communications · 2024Article
- Article
- A Study on the Robustness and Stability of Explainable Deep Learning in an Imbalanced Setting: The Exploration of the Conformational Space of G Protein-Coupled Receptors.International journal of molecular sciences · 2024Article
- Tutorial on how to build non-Markovian dynamic models from molecular dynamics simulations for studying protein conformational changes.The Journal of chemical physics · 2024Article
144 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
Simulations can provide tremendous insight into the atomistic details of biological mechanisms, but micro- to millisecond timescales are historically only accessible on dedicated supercomputers. We demonstrate that cloud computing is a viable alternative that brings long-timescale processes within reach of a broader community. We used Google's Exacycle cloud-computing platform to simulate two milliseconds of dynamics of a major drug target, the G-protein-coupled receptor β2AR. Markov state models aggregate independent simulations into a single statistical model that is validated by previous computational and experimental results. Moreover, our models provide an atomistic description of the activation of a G-protein-coupled receptor and reveal multiple activation pathways. Agonists and inverse agonists interact differentially with these pathways, with profound implications for drug design.
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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.