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April 2022 Ono Enters into Collaboration Agreement with Domain Therapeutics and Université de Montréal (Strasbourg, France; CEO: Pascal Neuville; “Domain”) and Université de Montréal (Québec, Canada; “UdM

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the kinetic factors that enhance in vivo efficacy beyond traditional potency metrics, as presented by Dr Dr. That's exactly what Dr. Dr. Submit your paper today to secure your work in Volume II ➤ Why Dr.

🌟The Dr. GPCR event of the year is the 3rd edition of the Summit. Become a Dr. GPCR Ecosystem site member to attend the Summit, it’s free!

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July 2022 "I’m happy to share that I’m starting a new position as Scientific co-founder LASEREDD Therapeutics" Ross Bathgate Read more at the source #DrGPCR #GPCR #IndustryNews

A Broader Lens: Dr. GPCR As the co-founder of Dr.

Dr. Learn how to transform your program from a series of disconnected efforts into a predictable, de-risked Register and join your colleagues in September ➤ Why Dr. GPCR Premium Membership Gives You an Edge In a world filled with noise, Dr. ” - DrGPCR University Course Attendee Get a competitive advantage—Join Dr.

Tomorrow is the day for another Dr. GPCR Virtual Cafe. This time with none other than Dr. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

June 2022 "We’re delighted to welcome Dr Ed Brennan as our new Vice President, Head of Clinical Development Dr Brennan has extensive experience across all phases of clinical development, and across multiple therapeutic

November 2021 Read more at the source #DrGPCR #GPCR #IndustryNews

Excited to hear Dr. Register here (FREE) https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe #drgpcr #gpcr #virtualcafe

Excited to hear Dr. automated micro-plate-based methods for quantifying #GPCR activation. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe

Come attend this month's virtual café talk to see the awesome work of Dr. Register here (FREE) https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

Join us and learn how to quantify your kinetic GPCR signaling from the expert himself: Dr. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

November 2021 "So proud and grateful to receive honorary doctorate yesterday from Karolinska Institute and celebrate with my family in Stockholm." Read more at the source #DrGPCR #GPCR #IndustryNews

Be sure to signup for the next Virtual Cafe of Dr. GPCR on the 24th of June! This time, the GPCRdb team ( Dr. David Gloriam , Dr. Reserve your spot for free at: https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #GPCR #GPCRs #DrGPCR

Join us for a fantastic introduction to GPCRdb with Dr. David Gloriam and Dr. Albert Kooistra. Register today: https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

April 2022 Read more at the source #DrGPCR #GPCR #IndustryNews

Did you register for our next Dr. GPCR Virtual Cafe? Register today! Addgene's Dr. research or you want to share your materials, this is the place to go. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe

Join us for the first virtual cafe talk to hear about the amazing work that Dr. Brian Arey is doing. https://www.ecosystem.drgpcr.com/dr-gpcr-virtual-cafe/ #gpcr #drgpcr #virtualcafe

the Department of Biochemistry and Molecular Medicine of the Faculty of Medicine of the Université de

September 2022 "Morphine, the most widely used analgesic, relieves severe pain by activating the μ-opioid receptor (MOR), whereas naloxone, with only slight structural changes compared to morphine, exhibits inhibitory effect, and is used to treat opioid abuse. The mechanism by which the MOR distinguishes between the two is unclear. Molecular dynamics (MD) simulations on a 1-μs time scale and metadynamics-enhanced conformational sampling are used here to determine the different interactions of these two ligands with MOR: morphine adjusted its pose by continuously flipping deeper into the pocket, whereas naloxone failed to penetrate deeper because its allyl group conflicts with several residues of MOR. The endogenous peptide ligand endomorphin-1 (EM-1) underwent almost no significant conformational changes during the MD simulations. To validate these processes, we employed GIRK4S143T, a MOR-activated Gβγ-protein effector, in combination with mutagenesis and electrophysiological recordings. We verified the role of some key residues in the dynamic recognition of naloxone and morphine and identified the key residue I322, which leads to differential recognition of morphine and naloxone while assisting EM-1 in activating MOR. Reducing the side chain size of I322 (MORI322A) transformed naloxone from an inhibitor directly into an agonist of MOR, and I322A also significantly attenuated the potency of MOR on EM-1, confirming that binding deep in the pocket is critical for the agonistic effect of MOR. This finding reveals a dynamic mechanism for the response of MOR to different ligands and provides a basis for the discovery of new ligands for MOR at the atomic level." Read more at the source #DrGPCR #GPCR #IndustryNews

Before the advent of AlphaFold, homology modeling was the most common method for predicting G protein-coupled receptor (GPCR) structures, especially when experimental data were limited. Homology modeling relies on using the known structure of a homologous protein as a template to model the target protein ( Carlsson, J. et al., 2011 ). However, this method has limitations: its accuracy is heavily dependent on the availability and quality of the template structure. For proteins with low sequence similarity to available templates, homology models tend to be less accurate, a notable challenge for GPCRs. GPCRs are dynamic, switching between multiple conformations, and many have only distant homologs with resolved structures, making accurate predictions difficult. The introduction of AlphaFold2 marked a major advancement in the field of GPCR structure prediction. AlphaFold2 uses an AI-driven approach that eliminates the need for structural templates, allowing it to predict structures for GPCRs that were previously difficult to model due to their low sequence homology to known structures. In a recent study on TAAR1, a GPCR linked to central nervous system disorders, researchers compared the performance of AlphaFold and homology models in virtual screening efforts (Diaz-Holguin, A. et al., 2024). The results were striking: AlphaFold2 outperformed homology models, achieving a 60% hit rate for compounds targeting TAAR1, more than double that of the homology models. The AlphaFold-predicted models revealed distinct ligand-binding site shapes, enabling the prioritization of different chemotypes during docking. One of the identified TAAR1 agonists demonstrated promising antipsychotic-like effects in rodent models, reinforcing the value of AlphaFold in drug discovery, especially when experimental structures are unavailable. While AlphaFold2’s ability to predict static structures was groundbreaking, however, GPCRs are highly dynamic proteins and continuously adopt different conformations based on their interactions with ligands and the cellular environment which are crucial for understanding how drugs can selectively target different receptor conformations to achieve therapeutic effects. AlphaFold3, the latest version, has improved on this by modeling interactions with various compounds, including natural ligands, ions, DNA, and RNA. However, AlphaFold3 faces challenges with synthetic ligands, which are central to pharmaceutical development. It excels in modeling interactions with natural ligands but struggles to generalize this accuracy to synthetic compounds, limiting its utility in drug discovery involving novel drug-like molecules. While AlphaFold provides an excellent foundation for generating hypotheses in drug discovery, it is not a standalone solution. To fully understand GPCR behavior and optimize drug targeting across multiple receptor states, experimental validation such as X-ray crystallography, cryo-EM or NMR are still essential for confirming predictions, refining models, and exploring the functional states of GPCRs. Additional kinetic validations must also be verified to comprehend the functions of the proteins. Future iterations of AlphaFold, or its integration with other computational techniques, could help overcome these limitations, leading to more comprehensive models that bridge the gap between computational predictions and real-world data. References: Carlsson, J.  et al.  Ligand discovery from a dopamine D3 receptor homology model and crystal structure. Nat Chem Biol   7 , 769-778 (2011).   https://doi.org/10.1038/nchembio.662 Diaz-Holguin, A.  et al.  AlphaFold accelerated discovery of psychotropic agonists targeting the trace amine-associated receptor 1. Sci Adv   10 , eadn1524 (2024).   https://doi.org/10.1126/sciadv.adn1524

For Dr. In this episode of the Dr. ” — Dr. Maria Majellaro Maria’s career didn’t start with a desire to launch a company. A postdoc in Santiago de Compostela introduced her to GPCRs, and from there, things escalated quickly Celtarys Research, now partnering with Dr.

This week at Dr. Dr. Led by Dr. Tom Sakmar and Dr. conversation dives deep into the tools now transforming receptor biology—and how they’re being used to de-orphanize

Dr. Save the date: February 8 - 29: Join Dr. GPCR University's live Zoom sessions hosted by Dr. GPCR Ecosystem group, where you can find Dr. Kenakin and Dr. GPCR Access to Dr. Receptor (GIPR) Revealed by Trapped-Ion-Mobility Spectrometry Coupled to Time-of-Flight Mass Spectrometry (TIMS-TOF

Secure Your Access Now ➤ 🗣️ “Thank you for bringing this (Principles of Pharmacology I) course with Dr I wish Dr. best for the sake of promoting more educational opportunities that are sorely needed in the field” — Dr GPCR University Learner Dr. GPCR Podcast - Surviving Discovery’s Gauntlet Dr. The Dr. GPCR Team Read Full Edition ➤

Explore 10 on-demand lessons by Dr. GPCR consulting that cuts through the noise, designing assay cascades, setting go/no-go points, and de-risking Visit Yamina’s Corner Now CELT-335 - Celtarys Validates New Assay for CB1/CB2 Screening Dr. Stay curious,   The Dr. GPCR Team Join Our Newsletter!