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Additionally, pull-down experiments demonstrated that YM promotes similar conformational changes in both

December 2021 "30/11/2021 Confo will work together with Regeneron to apply its GPCR drug discovery VIB spin-off Confo Therapeutics today announced that it has entered into a collaborative agreement with Regeneron Pharmaceuticals, Inc. whereby Confo’s technology platform, which uses conformationally selective VHH antibodies – ConfoBodies® – to stabilize GPCRs (G protein-coupled receptors) in disease-relevant conformations

October 2022 "Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP" Read more at the source #DrGPCR #GPCR #IndustryNews

April 2022 Sosei Heptares Confirms Senior Leadership Changes to Drive the Company Through the Next Stage , Japan and Cambridge, UK, 24 March 2022 – Sosei Group Corporation (“the Company”; TSE: 4565) today confirms

September 2022 "Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP." Read more at the source #DrGPCR #GPCR #IndustryNews

Mark Connor! Learn more about #GPCRs and life as an academic wearing different hats.

Here, molecular dynamics simulations are employed to explore the implied mechanism of the enhanced sensitivity

GPCR activation typically occurs through the binding of agonists which stabilize receptor conformations GPCRs are present in a range of conformations, and the binding of a ligand, as well as interactions with signaling molecules like G proteins, can selectively stabilize specific conformations (Gether 2000). , preventing access to others, or allowing previously inaccessible conformations. To understand how ligands or drugs affect GPCRs is crucial to grasp the dynamics of these conformational

September 2022 Lysine 101 in the CRAC Motif in Transmembrane Helix 2 Confers Cholesterol-Induced Thermal experimental and simulation approaches, that membrane cholesterol acts as a key regulator of organization, dynamics a cholesterol recognition/interaction amino acid consensus (CRAC) motif in transmembrane helix 2 in conferring

Nbs are useful tools for dynamic biological systems; they have been used to crystallize flexible membrane They have also been used as biosensors to monitor conformational changes of GPCRs in living cells. Binding to cryptic epitopes and conformational selection: Nanobodies have a unique shape that allows Nbs can stabilize specific conformations of proteins, including unstable structural intermediates and This allows for correlating structural or dynamic features observed in vitro with functional observations

that the structures of GPCRs bound to these interaction partners available today do not reveal a clear conformational In view of this, three possibilities are conceivable: (i) there are no generalizable GPCR conformations easily detectable in the receptor-transducer structures determine partner preference; or (iii) the dynamics

2022 "Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) lipids have been shown to stabilize an active conformation For class B GPCRs, previous molecular dynamics (MD) simulation studies have shown PI(4,5)P2 interacting Specifically, we find the PI(4,5)P2 lipids to have a higher affinity toward the inactive conformation Interestingly, we find that in contrast to class A GPCRs, PI(4,5)P2 appear to stabilize the inactive conformation

Here, we investigate the conformational changes induced by the binding of a nanobody (Nb80) on the active-like β2 adrenergic receptor (β2AR) via enhanced sampling molecular dynamics simulations. helix 6 and a close proximity of transmembrane (TM) helices 5 and 7, and favors the fully active-like conformation Besides, ligand-specific subtle differences in the conformations assumed by intracellular loop 2 and Dynamic network analysis further reveals that Nb80 binding triggers tighter and stronger local communication

and a middle sized flexible molecule "A GA-guided multidimensional virtual-system coupled molecular dynamics Then sampling was conducted from conformations where bosentan was distant from the binding site in the The deepest basin in the resultant free-energy landscape was assigned to native-like complex conformation The bosentan-captured conformations by the tip-region and root-region of the N-terminal tail correspond

March 2022 " Geneva, Switzerland, March 7, 2022 – Addex Therapeutics (SIX: ADXN, Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, announced today that it will issue its full-year 2021 financial results on Thursday, March 10, 2022. Tim Dyer , CEO, Roger Mills , CMO and Robert Lütjens , Head of Discovery Biology, will provide a business update and review its pipeline during a teleconference and webcast for investors, analysts and media at 16:00 CET (15:00 GMT / 10:00 EST / 07:00 PST) the same day. " Read more at the source #DrGPCR #GPCR #IndustryNews

Analyses reveal similar overall complex architecture, with local conformational differences. Molecular dynamics simulations support the local conformational flexibilities and different stabilities

glutamate receptors Molecular Basis of MC1R Activation: Mutation-Induced Alterations in Structural Dynamics SNX25 as a novel regulator of GPCR-G protein signaling from endosomes Cellular lipids regulate the conformational cancer Distinct Activation Mechanisms of CXCR4 and ACKR3 Revealed by Single-Molecule Analysis of their Conformational anterograde transport of nascent G protein-coupled receptors Effects of an external static EF on the conformational transition of 5-HT1A receptor: A molecular dynamics simulation study Monitoring norepinephrine release

July 2022 Confo Therapeutics receives €1.7 million VLAIO grant for further research on GPCR modulators for rare diseases "29/06/2022 Confo Therapeutics , founded in 2015 as a spin-off from VIB and VUB, announced The grant should help expand Confo Therapeutic ’s research on G protein-coupled receptor (GPCR) drug

study Xin Cai et al. highlight the importance of GPCR dimers in drug discovery referring to important conformational But what are the conformation changes that drive GPCR dimerization? The interaction between two receptors in a dimer involves a conformational change in the transmembrane Interestingly, the amplitude of the conformational changes due to ligand binding is limited at these How dynamic are GPCRs dimer interfaces?

Atomistic molecular dynamics simulations of opsin in a lipid membrane reveal conformational transitions Conformational changes that facilitate scrambling are distinct from those associated with GPCR signaling

how various factors, such as lipid composition, osmotic stress, and allosteric ligands, modulate the conformational dynamics of GPCRs remains crude. The Nobel Prize in Chemistry 2012 - Popular information - NobelPrize.org. https://www.nobelprize.org /prizes/chemistry/2012/popular-information/. 66. /prizes/chemistry/2012/advanced-information/. 67.

., for their research on Intracellular pocket conformations, determine signaling through the μ opioid preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage Intracellular pocket conformations Taste Dissecting a Brake for Airway Smooth Muscle Cell Movement Hepatic extracellular ATP/adenosine dynamics Modulator Therapeutics for Neurological Disorders Aelis Farma Reports Its 2023 Annual Financial Resultsand Confirms 20th Annual PEGS Boston Summit May 16 - 19, 2024 | ASPET 2024 May 27 - 29, 2024 | SLAS Europe 2024 Conference

Conformational changes between inactive and active states are facilitated by a "microswitch network" All CKRs studied show the canonical active conformation, except CX3CR1 which displays a significantly As a result of the unique active conformation, the residues in the microswitch network show non-canonical Comparison between the active and inactive structures reveal conformational shifts that mirror the activation crucial binding feature is the E19845.51–NH2 salt bridge (Nelson, Boyd et al. 2001), with molecular dynamics

March 2022 Confo Therapeutics Doses First Subjects In Phase 1 Clinical Trial Of CFTX-1554 For The Treatment Of Neuropathic Pain " — Confo’s first drug candidate moves into clinical development — Ghent, Belgium – March 10, 2022 – Confo Therapeutics , a leader in the discovery of medicines targeting G-protein coupled

Through (un)biased molecular dynamics simulations and mutagenesis experiments, we show that TM2 rearrangement rearrangement in favor of receptor activation and increasing the population of receptors that adopt an active conformation

hormone type 1 receptor (PTHR) as a prototypic class B GPCR target, and a combination of molecular dynamics Here we found a key mechanical site that modulates the collective dynamics of the receptor and used this ensemble of PTHR conformers to identify selective small molecules with strong negative allosteric and

Let’s dive into the Classified GPCR News from January 8th to 14th, 2024 Adhesion GPCRs Conformational and Signaling Biased Signaling in Mutated Variants of β2-Adrenergic Receptor: Insights from Molecular Dynamics analysis, engineering, and targeting Structural and Molecular Insights into GPCR Function Characterizing conformational Predictive Modelling NanoImaging Services Appoints John Rigg as Chief Executive Officer Unraveling GPCRs Conformations Webinars January 16 - 19, 2024 | 23rd Annual PEP Talk February 3 - 7, 2024 | SLAS2024 International Conference