Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs

No abstract is available for this paper.

• Publication year

  2013

• Venue

  Nature

• Publication date

  2013-10-13

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1038/nature12595PMID 24121438
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Structure-based drug screening for G-protein-coupled receptors.

  2012cited by this paper
• Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions

  2012cited by this paper
• Structure and Dynamics of the M3 Muscarinic Acetylcholine Receptor

  2012cited by this paper
• The allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling

  2012cited by this paper
• Crystal Structure of the β2Adrenergic Receptor-Gs protein complex

  2011cited by this paper
• Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations

  2011cited by this paper
• Crystal structure of metarhodopsin II

  2011cited by this paper
• How does a drug molecule find its target binding site?

  2011cited by this paper
• Allosteric modulation of G protein-coupled receptors: a pharmacological perspective.

  2011cited by this paper
• How robust are protein folding simulations with respect to force field parameterization?

  2011cited by this paper
• Pathway and mechanism of drug binding to G-protein-coupled receptors

  2011cited by this paper
• Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist

  2011cited by this paper
• Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types.

  2010cited by this paper
• Allosteric Modulation of Muscarinic Acetylcholine Receptors

  2010cited by this paper
• Atomic-Level Characterization of the Structural Dynamics of Proteins

  2010cited by this paper
• The Tetrahydroisoquinoline Derivative SB269,652 Is an Allosteric Antagonist at Dopamine D3 and D2 Receptors

  2010cited by this paper
• Structure and Function of an Irreversible Agonist-β2 Adrenoceptor complex

  2010cited by this paper
• Allosteric Modulation of G Protein Coupled Receptors by Cytoplasmic, Transmembrane and Extracellular Ligands

  2010cited by this paper
• Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation

  2009cited by this paper
• Millisecond-scale molecular dynamics simulations on Anton

  2009cited by this paper
• Identification of two distinct inactive conformations of the β2-adrenergic receptor reconciles structural and biochemical observations

  2009cited by this paper
• Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders.

  2009cited by this paper
• CHARMM general force field: A force field for drug‐like molecules compatible with the CHARMM all‐atom additive biological force fields

  2009cited by this paper
• Flexible ligand docking to multiple receptor conformations: a practical alternative.

  2008cited by this paper
• Structure-Function Studies of Allosteric Agonism at M2 Muscarinic Acetylcholine Receptors

  2007cited by this paper
• Critical Role for the Second Extracellular Loop in the Binding of Both Orthosteric and Allosteric G Protein-coupled Receptor Ligands*

  2007cited by this paper
• Allosteric Interactions with Muscarinic Acetylcholine Receptors: Complex Role of the Conserved Tryptophan M2422Trp in a Critical Cluster of Amino Acids for Baseline Affinity, Subtype Selectivity, and Cooperativity

  2006cited by this paper
• Gaussian split Ewald: A fast Ewald mesh method for molecular simulation.

  2005cited by this paper
• Critical Amino Acid Residues of the Common Allosteric Site on the M2 Muscarinic Acetylcholine Receptor: More Similarities than Differences between the Structurally Divergent Agents Gallamine and Bis(ammonio)alkane-Type Hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)ammonium]dibromide

  2005cited by this paper
• Extending the treatment of backbone energetics in protein force fields: Limitations of gas‐phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations

  2004cited by this paper
• Application of a Kinetic Model to the Apparently Complex Behavior of Negative and Positive Allosteric Modulators of Muscarinic Acetylcholine Receptors

  2004cited by this paper
• Identification of essential residues involved in the allosteric modulation of the human A(3) adenosine receptor.

  2003cited by this paper
• Interactions of orthosteric and allosteric ligands with [3H]dimethyl-W84 at the common allosteric site of muscarinic M2 receptors.

  2003cited by this paper
• Allosteric site on muscarinic acetylcholine receptors: identification of two amino acids in the muscarinic M2 receptor that account entirely for the M2/M5 subtype selectivities of some structurally diverse allosteric ligands in N-methylscopolamine-occupied receptors.

  2003cited by this paper
• N+/Si replacement as a tool for probing the pharmacophore of allosteric modulators of muscarinic M2 receptors: Synthesis, allosteric potency, and positive cooperativity of silicon-based W84 derivatives

  2002cited by this paper
• The PyMOL Molecular Graphics System

  2002cited by this paper
• Analogs of WIN 62,577 define a second allosteric site on muscarinic receptors.

  2002cited by this paper
• A fast SHAKE algorithm to solve distance constraint equations for small molecules in molecular dynamics simulations

  2001cited by this paper
• Electrostatics of nanosystems: Application to microtubules and the ribosome

  2001cited by this paper
• Site-directed mutagenesis reveals two epitopes involved in the subtype selectivity of the allosteric interactions of gallamine at muscarinic acetylcholine receptors.

  1999cited by this paper
• All-atom empirical potential for molecular modeling and dynamics studies of proteins.

  1998cited by this paper
• VMD: visual molecular dynamics.

  1996cited by this paper
• Cation-.pi. Interactions: Nonadditive Effects Are Critical in Their Accurate Representation

  1995cited by this paper
• Detection, quantitation, and verification of allosteric interactions of agents with labeled and unlabeled ligands at G protein-coupled receptors: interactions of strychnine and acetylcholine at muscarinic receptors.

  1995cited by this paper
• [19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors

  1995cited by this paper
• Probing of the location of the allosteric site on m1 muscarinic receptors by site-directed mutagenesis.

  1995cited by this paper
• Protonation states of membrane-embedded carboxylic acid groups in rhodopsin and metarhodopsin II: a Fourier-transform infrared spectroscopy study of site-directed mutants.

  1993cited by this paper
• Host-guest supramolecular chemistry. 34. The incremental approach to noncovalent interactions: coulomb and van der Waals effects in organic ion pairs

  1992cited by this paper
• Reversible multiple time scale molecular dynamics

  1992cited by this paper
• Structure of a potent neuromuscular blocking agent: Caracurine-II dimethochloride octahydrate, [C40H44N4O2]2+·2CI−·8H2O

  1985cited by this paper
• 221. The constitution of aspidospermine. Part III. Reactivity at the nitrogen atoms, and biogenetic considerations

  1957cited by this paper
• The constitution of aspidospermine

  1948cited by this paper

• Nanobodies unlock new mechanisms to target G protein-coupled receptors.

  2026cites this paper
• Dualsteric and dual-acting modulation of muscarinic receptors by antagonist KH-5

  2026cites this paper
• A Review of In Silico Approaches for Discovering Natural Viral Protein Inhibitors in Aquaculture Disease Control.

  2025cites this paper
• Cryo-EM reveals a new allosteric binding site at the M5 mAChR

  2025cites this paper
• Agonism and Biased Signaling.

  2025cites this paper
• Beyond the 1:1 Ligand–Protein Paradigm: An In Silico Assay for Competitive Ligand Binding

  2025cites this paper
• A Transferable and Robust Computational Framework for Class A GPCR Activation Free Energies

  2025cites this paper
• Identification of allosteric sites and ligand-induced modulation in the dopamine receptor through large-scale alchemical mutation scan

  2025cites this paper
• Resistance to Allosteric Inhibitors.

  2025cites this paper
• Enhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation

  2025cites this paper
• Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery

  2025cites this paper
• Development of Shell-Space Electrostatic Potential Fitting Charges in a United-Atom Model for Amino Acids Simulations.

  2025cites this paper
• Cryo-EM reveals an extrahelical allosteric binding site at the M5 mAChR

  2025cites this paper
• Positive allosteric modulation of a GPCR ternary complex

  2024cites this paper
• MEF-AlloSite: an accurate and robust Multimodel Ensemble Feature selection for the Allosteric Site identification model

  2024cites this paper
• Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode

  2024cites this paper
• Exploring novel Kokumi peptides in Agaricus bisporus: selection, identification, and tasting mechanism investigation through sensory evaluation and computer simulation analysis.

  2024cites this paper
• AlloPool: An Adaptive Graph Neural Network for Dynamic Allosteric Network Prediction in Protein Systems

  2024cites this paper
• Identification of a Novel Subtype-Selective α1B-Adrenoceptor Antagonist

  2024cites this paper
• Exploring Conformational Landscapes Along Anharmonic Low-Frequency Vibrations.

  2024cites this paper
• The Art and Science of Molecular Docking.

  2024cites this paper
• Molecular dynamics-based identification of binding pathways and two distinct high-affinity sites for succinate in succinate receptor 1/GPR91.

  2024cites this paper
• Synthesis, Spectroscopic Analysis, Molecular Docking and DFT Study of Novel 1,2,3-Triazole Derivatives Incorporating paramethoxythymol and Salicylaldehyde Moieties

  2024cites this paper
• Bivalent and bitopic ligands of the opioid receptors: The prospects of a dual approach

  2024cites this paper
• Differential Behavior of Conformational Dynamics in Active and Inactive States of Cannabinoid Receptor 1

  2024cites this paper
• The Inferential Binding Sites of GCGR for Small Molecules Using Protein Dynamic Conformations and Crystal Structures

  2024cites this paper
• Molecular Dynamics and Docking Investigation of Flavonol Aglycones against Sulfonylurea Receptor 1 (SUR1) for Anti–diabetic Drug Design

  2024cites this paper
• Potential allosteric pockets identification of glucagon receptor based on molecular dynamics simulations.

  2024cites this paper
• M1/M4 receptors as potential therapeutic treatments for schizophrenia: A comprehensive study.

  2024cites this paper
• Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Muscarinic M3 Receptor‐Positive Allosteric Modulator ASP8302 Following Single and Multiple Ascending Oral Doses in Healthy Volunteers

  2024cites this paper
• The value of protein allostery in rational anticancer drug design: an update

  2024cites this paper
• Comparative in-silico analysis of vitexin and orientin as potential antiphotoaging agents against MMP enzymes

  2024cites this paper
• Reaction Coordinates Are Optimal Channels of Energy Flow.

  2024cites this paper
• Alchemical Transformations and Beyond: Recent Advances and Real-World Applications of Free Energy Calculations in Drug Discovery

  2024cites this paper
• A non-canonical mechanism of GPCR activation

  2024cites this paper
• Differential Behavior of Conformational Dynamics in Active and Inactive States of Cannabinoid Receptor 1

  2024cites this paper
• Molecular docking-based interaction studies on imidazo[1,2-a] pyridine ethers and squaramides as anti-tubercular agents

  2023cites this paper
• Specifics of Metabolite-Protein Interactions and Their Computational Analysis and Prediction.

  2023cites this paper
• Allosteric Sites and Allosteric Regulators of G Protein-Coupled Receptors: Gray Cardinals of Signal Transduction

  2023cites this paper
• Deep Learning Dynamic Allostery of G-Protein-Coupled Receptors

  2023cites this paper
• Deep Learning Dynamic Allostery of G-Protein-Coupled Receptors

  2023cites this paper
• Ligand selectivity hotspots in serotonin GPCRs.

  2023cites this paper
• Is the Functional Response of a Receptor Determined by the Thermodynamics of Ligand Binding?

  2023cites this paper
• Machine Learning in Transition State Searching for Complex Biomolecules

  2023cites this paper
• Allosteric modulation of gonadotropin receptors

  2023cites this paper
• GPCR Allostery: a View from Computational Biology.

  2023cites this paper
• A non-canonical mechanism of GPCR activation

  2023cites this paper
• Structure and Molecular Mechanism of Signaling for the Glucagon-like Peptide-1 Receptor Bound to Gs Protein and Exendin-P5 Biased Agonist.

  2023cites this paper
• Long Time Scale Ensemble Methods in Molecular Dynamics: Ligand–Protein Interactions and Allostery in SARS-CoV-2 Targets

  2023cites this paper
• Exploring the Role of Molecular Dynamics Simulations in Most Recent Cancer Research: Insights into Treatment Strategies

  2023cites this paper
• Recessive CHRM5 variant as a potential cause of neurogenic bladder

  2023cites this paper
• Deep Learning Dynamic Allostery of G-Protein-Coupled Receptors

  2023cites this paper
• Role of Conserved Tyrosine Lid Residues in the Activation of the M2 Muscarinic Acetylcholine Receptor

  2023cites this paper
• Structural and dynamic insights into supra-physiological activation and allosteric modulation of a muscarinic acetylcholine receptor

  2023cites this paper
• Stability Analysis of the Asiatic Acid-COX-2 Complex Using 100 ns Molecular Dynamic Simulations and Its Selectivity against COX-2 as a Potential Anti-Inflammatory Candidate

  2023cites this paper
• A Sleep‐Specific Midbrain Target for Sevoflurane Anesthesia

  2023cites this paper
• Opportunities and challenges for the development of M1 muscarinic receptor positive allosteric modulators in the treatment for neurocognitive deficits

  2022cites this paper
• Development of enhanced conformational sampling methods to probe the activation landscape of GPCRs.

  2022cites this paper
• Allosteric Modulators of Dopamine D2 Receptors for Fine-Tuning of Dopaminergic Neurotransmission in CNS Diseases: Overview, Pharmacology, Structural Aspects and Synthesis

  2022cites this paper
• ES-Screen: A Novel Electrostatics-Driven Method for Drug Discovery Virtual Screening

  2022cites this paper
• Predictive Molecular Models for Charged Materials Systems: From Energy Materials to Biomacromolecules

  2022cites this paper
• Systematic analysis of biomolecular conformational ensembles with PENSA.

  2022cites this paper
• MISPR: an open-source package for high-throughput multiscale molecular simulations

  2022cites this paper
• Molecular simulations of proteins: From simplified physical interactions to complex biological phenomena.

  2022cites this paper
• Allosteric modulation of GPCRs: From structural insights to in silico drug discovery.

  2022cites this paper
• Challenges and frontiers of computational modelling of biomolecular recognition

  2022cites this paper
• Pre‐Training of Equivariant Graph Matching Networks with Conformation Flexibility for Drug Binding

  2022cites this paper
• Inhibition of Biotin Carboxylase by Three Antibacterial Compounds

  2022cites this paper
• Subsets of Slow Dynamic Modes Reveal Global Information Sources as Allosteric Sites.

  2022cites this paper
• Applications of Molecular Dynamics Simulation in Protein Study

  2022cites this paper
• Muscarinic M3 positive allosteric modulator ASP8302 enhances bladder contraction and improves voiding dysfunction in rats

  2022cites this paper
• Fly casting with ligand sliding and orientational selection supporting complex formation of a GPCR and a middle sized flexible molecule

  2022cites this paper
• Mechanistic insight into the impact of a bivalent ligand on the structure and dynamics of a GPCR oligomer

  2022cites this paper
• Pre-training Protein Models with Molecular Dynamics Simulations for Drug Binding

  2022cites this paper
• Computational Medicinal Chemistry to Target GPCRs

  2022cites this paper
• Drug specificity and affinity are encoded in the probability of cryptic pocket opening in myosin motor domains

  2022cites this paper
• Rational design of allosteric modulators: Challenges and successes

  2021cites this paper
• Symmetric and Asymmetric Models for the Arabidopsis thaliana Plasma Membrane: A Simulation Study.

  2021cites this paper
• Temperature artifacts in protein structures bias ligand-binding predictions

  2021cites this paper
• Identification of a Novel Allosteric Site at the M5 Muscarinic Acetylcholine Receptor

  2021cites this paper
• Neurosteroids and steroid hormones are allosteric modulators of muscarinic receptors.

  2021cites this paper
• Along the allostery stream: Recent advances in computational methods for allosteric drug discovery

  2021cites this paper
• Protein Structure, Dynamics and Assembly: Implications for Drug Discovery

  2021cites this paper
• Fundamentals of molecular modeling

  2021cites this paper
• Potentiation of Muscarinic M3 Receptor Activation through a New Allosteric Site with a Novel Positive Allosteric Modulator ASP8302

  2021influential citation
• Cation-π interactions and their functional roles in membrane proteins.

  2021cites this paper
• A lysine–cysteine redox switch with an NOS bridge regulates enzyme function

  2021cites this paper
• Membrane-Facilitated Receptor Access and Binding Mechanisms of Long-Acting β2-Adrenergic Receptor Agonists

  2021cites this paper
• Lean-Docking: Exploiting Ligands' Predicted Docking Scores to Accelerate Molecular Docking

  2021cites this paper
• Observing spontaneous, accelerated substrate binding in molecular dynamics simulations of glutamate transporters

  2021cites this paper
• Multisite Model of Allosterism for the Adenosine A1 Receptor

  2021cites this paper
• Biomolecular Modeling and Simulation: A Prospering Multidisciplinary Field.

  2021cites this paper
• An allosteric ligand stabilizes distinct conformations in the M2 muscarinic acetylcholine receptor

  2021cites this paper
• Allosteric coupling and biased agonism in G protein‐coupled receptors

  2021cites this paper
• Pathways and Mechanism of Caffeine Binding to Human Adenosine A2A Receptor

  2021cites this paper
• Trends in application of advancing computational approaches in GPCR ligand discovery

  2021cites this paper
• Dynamic Coupling of Tyrosine 185 with the Bacteriorhodopsin Photocycle, as Revealed by Chemical Shift Assisted AF-QM/MM Calculations and Molecular Dynamic Simulations

  2021cites this paper
• Allostery of atypical modulators at oligomeric G protein-coupled receptors

  2021cites this paper
• Tetracycline Derivatives Inhibit Plasmodial Cysteine Protease Falcipain-2 through Binding to a Distal Allosteric Site

  2021cites this paper
• Current Advances in Allosteric Modulation of Muscarinic Receptors

  2020cites this paper