Receptor Mechanisms and Signaling

This paper identifies a helix 8-proximate allosteric site in GPR84 and shows how it enables Gi-biased signalling through structural and dynamic mechanisms.

This paper introduces MGS, a computational method to detect ligand signaling bias in GPCR systems by analyzing conformational changes linked to specific signaling pathways.

This study investigates β2AR signaling through Gs and G15 in macrophages, showing differential activation and effects on polarization and repair-related gene expression.

The paper presents a dynamic pocketome analysis of TAAR receptors using simulations, revealing receptor-specific ligand-receptor interplay and plasticity in binding sites.

This study designs a chimeric adenylyl cyclase (AC95) to investigate isoform-specific regulation, revealing structural insights and drug target possibilities.

The paper shows that FFA2R modulates NADPH oxidase activity induced by FPR agonists, revealing distinct signaling pathways activated by FPRs.

The paper introduces the GPCR Evolution Database, which provides evolutionary analysis of GPCRs to study their function and conservation across species.

The paper investigates how mutations in the hA2AR receptor affect ZM241385 dissociation by altering the interaction network involving water and membrane lipids.

The paper uses computational and experimental methods to identify transition intermediates in the μ-opioid receptor-Gi protein complex that encode ligand efficacy.

The paper identifies ligands with varying steric profiles that exhibit different β-arrestin recruitment capacities at GPR84, revealing a mechanism for controlling signaling bias.

The paper reports cryo-EM structures of melanocortin receptors bound to endogenous inverse agonists, revealing mechanisms of inverse agonism and subtype selectivity.

The paper annotates neuropeptides and GPCRs in Gryllus bimaculatus and predicts ligand-receptor pairs using AlphaFold3 and Boltz-2, providing a resource for studying insect endocrinology.

The paper identifies allosteric pathways that determine G protein coupling selectivity in promiscuous GPCRs using a combination of mutagenesis, simulations, and machine learning.

The paper uses molecular dynamics simulations to study how ligand binding at two sites of TAS2R14 affects receptor dynamics and chloride ion behavior.

The paper shows that intra-cluster receptor density (IRD) regulates TNFR1 signaling, with higher IRD activating and lower IRD impairing signaling.

This study shows that hormone oscillations maintain cellular responsiveness and coordination across cell types by allowing receptor resensitization and buffering kinetic variation.

The paper presents cryo-EM structures of GPR119 bound to OEA and G proteins, revealing structural basis for G protein selectivity and lipid recognition.

This study examines CBD interactions with fentanyl-bound MOR1 conformations using molecular dynamics simulations, finding state-dependent effects but limited inferential power due to small trajectory numbers.

This study identifies thermodynamic and kinetic factors that determine ligand selectivity between A2A and A2B adenosine receptors using computational simulations.

The paper presents cryo-EM structures of the delta opioid receptor with PAMs, identifies a novel allosteric site, and describes a mechanism for enhanced binding and activation.

The paper constructs an atlas of opioid receptor structures across ligands and transducers, revealing rewiring patterns and hydration features without identifying causal mechanisms.

The paper identifies microbial GAIN domains (MAIN) that undergo autoproteolysis, enabling release of surface-associated proteins in response to shear force.

This study determines the cryo-EM structure of GPR30 with bicarbonate ions, identifies key residues for activation, and provides insights into G-protein coupling and drug development.

This study investigates how lithocholic acid modulates GPBAR1 activation and G protein engagement through molecular dynamics simulations and structural analysis.

The paper shows that GPR27 mediates L-lactate-induced increases in intracellular calcium and cAMP in 3T3 cells, suggesting L-lactate may act as an endogenous ligand for GPR27.

This study compares the conformational diversity of α1A-Adrenoceptor in different membrane mimetics using NMR, showing that SNPs reduce conformational dynamics compared to detergents.

This paper develops a NanoBiT-based platform to systematically study multiple layers of GPCR signaling in living cells.

This study uses hydrogen-deuterium exchange mass spectrometry to analyze how non-peptide agonists and endogenous ligands modulate structural dynamics in a pre-coupled GLP-1R-Gs complex, revealing patterns linked to receptor activation.

This paper discovers NHAP, a fungal metabolite that selectively inhibits Gi-signaling, demonstrating functional blockade in cardiomyocytes without cytotoxicity.

The paper develops an interpretable machine learning model to identify allosteric modulators of the AT1R receptor and discovers a negative allosteric modulator.