ArticleNature chemical biology2020
Computational design of G Protein-Coupled Receptor allosteric signal transductions.
Article in Nature chemical biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 79 citations in OpenAlex.
- Molecular mechanisms of native ligand selectivity in catecholamine G protein-coupled receptors.Nature communications · 2026Article
- Accelerated Combinatorial Drug Design for Human Immunodeficiency Virus Resistance through Seeded Multisite λ-Dynamics.Journal of chemical theory and computation · 2026Article
- Computational design of synthetic receptors with programmable signalling activity for enhanced cancer T cell therapy.Nature biomedical engineering · 2026Article
- Transient ligand contacts of the intrinsically disordered N-terminus of neuropeptide YNature communications · 2025Article
- Generative Landscapes and Dynamics to Design Functional Multidomain Artificial Transmembrane Transporters.ACS central science · 2025Article
- Deep learning-guided design of dynamic proteins.Science (New York, N.Y.) · 2025Article
- Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.Nature reviews. Drug discovery · 2025Review
- Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.Nature chemistry · 2025Article
- Computational design of de novo bioenergetic membrane proteins.Biochemical Society transactions · 2024Review
- Taste Sensor Assessment of Bitterness in Medicines: Overview and Recent Topics.Sensors (Basel, Switzerland) · 2024Review
- Assessment of Bitterness in Non-Charged Pharmaceuticals with a Taste Sensor: A Study on Substances with Xanthine Scaffold and Allopurinol.Molecules (Basel, Switzerland) · 2024Article
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- Structure-based engineering of Tor complexes reveals that two types of yeast TORC1 produce distinct phenotypes.Journal of cell science · 2024Article
- Development of Taste Sensor with Lipid/Polymer Membranes for Detection of Umami Substances Using Surface Modification.Biosensors · 2024Article
- Review
- Molecular determinants of ligand efficacy and potency in GPCR signaling.Science (New York, N.Y.) · 2023Article
- Advances in ligand-specific biosensing for structurally similar molecules.Cell systems · 2023Review
- Computational design of dynamic receptor-peptide signaling complexes applied to chemotaxis.Nature communications · 2023Article
- Exploiting conformational dynamics to modulate the function of designed proteins.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Prediction of dynamic allostery for the transmembrane domain of the sweet taste receptor subunit, TAS1R3.Communications biology · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Membrane receptors sense and transduce extracellular stimuli into intracellular signaling responses but the molecular underpinnings remain poorly understood. We report a computational approach for designing protein allosteric signaling functions. By combining molecular dynamics simulations and design calculations, the method engineers amino-acid 'microswitches' at allosteric sites that modulate receptor stability or long-range coupling, to reprogram specific signaling properties. We designed 36 dopamine D2 receptor variants, whose constitutive and ligand-induced signaling agreed well with our predictions, repurposed the D2 receptor into a serotonin biosensor and predicted the signaling effects of more than 100 known G-protein-coupled receptor (GPCR) mutations. Our results reveal the existence of distinct classes of allosteric microswitches and pathways that define an unforeseen molecular mechanism of regulation and evolution of GPCR signaling. Our approach enables the rational design of allosteric receptors with enhanced stability and function to facilitate structural characterization, and reprogram cellular signaling in synthetic biology and cell engineering applications.
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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.