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March 2022 Crinetics Pharmaceuticals Expands Executive Team With Appointment Of James Hassard As Chief therapeutics for rare endocrine diseases and endocrine-related tumors, today announced the appointment of James Hassard as chief commercial officer. Hassard is a commercial leader with more than three decades of experience leading sales and marketing

Watch Episode 171 What happens when your protein has no known ligands, no structure, and very little data? For most researchers, that’s a dead end. For Alessandro Nicoli, it’s an opportunity. In this post, we explore how computational tools—especially AlphaFold —are helping crack the mystery of olfactory GPCRs , one of the most elusive receptor families in the human body. The Problem: Hundreds of Receptors, Almost No Ligands Alessandro’s work focuses on olfactory GPCRs—nearly 400 distinct receptors that play key roles in smell but remain largely uncharacterized . Most have only one known ligand, if any. Their structures are hard to determine experimentally due to poor expression and the volatility of odorant molecules. That’s where computational chemistry steps in. Enter AlphaFold: Predicting the “Face” of a Receptor When Alessandro began his PhD, structural models of olfactory GPCRs were essentially nonexistent. The main challenge was simple but daunting: “The challenge was to get a face to those proteins—the structure. AlphaFold has, of course, as we know, revolutionized the world.”  —Alessandro Nicoli For the first time, researchers had a reliable set of predicted structures to work from. That meant simulations, ligand screening, and experimental design could move forward with confidence. “When they released the first structure of the odorant receptors… AlphaFold already had it, without any prior information, and the match was very close to experimental error.”  —Alessandro Nicoli A New Era of GPCR Research AlphaFold didn’t just fill a gap—it shifted the focus of computational biology. Instead of struggling to predict structures from scratch, Alessandro and others could now use AI-generated models as starting points  for deeper questions. “…now you have a plethora of 400 models that you can start with molecular dynamics, docking, virtual screening.”  —Alessandro Nicoli The result? More accurate hypotheses, faster ligand discovery, and new strategies to tackle one of biology’s most complex receptor families. From Prediction to Discovery One of Alessandro’s projects focused on receptor R5VK1 , where his team tested computational models against a set of experimentally validated active and inactive ligands. By iteratively refining the models with docking and mutagenesis data, they developed predictive pipelines that can help identify new odorant ligands . This case study highlights why computational chemistry is no longer a side tool—it’s a driver of discovery , especially when experimental data is scarce. Want to level up your modeling skills? Start with our GPCR training program and get hands-on with virtual tools shaping the future of drug discovery. ________ Keyword Cloud: # AlphaFold #GPCRdata #DrugDiscovery #OlfactoryReceptors #StructuralBiology #ArtificialIntelligence #MolecularDynamics #ComputationalBiology #MolecularModeling

Biology, Vlaams Instituut Biotechnologie, at the Vrije Universiteit Brusle, Brussels, Belgium, has been named

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

Clark, Paul Ehrlich, Sir James Black, and more—sharing the stories and setbacks that shaped today’s scientific

signaling.[19–23] The 1988 Nobel Prize in Physiology or Medicine went to George Herbert Hitchings, Sir James Nobel Prize: Three Named for Medicine, Physiology Award. Sir James W. Sir James W. Sir James Whyte Black OM. 14 June 192422 March 2010.

time, the neurexins, another family of adhesion molecules that also happened to be targeted by the same The excitement I felt when I first attended back in Boston is the same one I feel now that I am the organizer Of course, there is the famous parade popularized by the James Bond movie Spectre.

For his postdoctoral training at Boston Children’s Hospital and Harvard Medical School, he joined the But the core is still the same: solve a hard problem that matters.

For Hodson, that moment came early. For Hodson, that moment came with a protein he’d been tracking for a decade: vitamin D binding protein The turning point came when the cryo-EM data arrived — a structure solved through the same collaborative

Eric Trinquet and his team at Revvity, that moment came when they watched GPCRs internalize in native Instead, the signal came clean, scalable, and unmistakably real. It wasn’t luck. That’s where collaboration came in. Access this week’s full Premium Edition here ➤ What our members say "This came at just the most perfect

But then came the industry shift. “Companies started shutting down neuroscience and GPCR programs.

The story behind how Dr.GPCR came to be, the people behind the process, the great anecdotes, and what

“The first time I wore my lucky cactus shirt to a major meeting... and it led to a game-changing collaboration

Kenakin’s latest lecture delivers a game-changing framework for teams grappling with the gap between permeability using modern, cost-effective pharmacokinetic assays   Why Intracellular GPCR Drugs Change the Game Same Affinity, Different Outcomes: Why Residence Time Matters More Two ligands. In a traditional assay, they look the same. But in vivo?

The turning point came from an unexpected source: a letter of recommendation. His introduction came through a practical suggestion: explore a new protein family that was gaining traction He came to see that effective GPCR research requires true interdisciplinary integration.

The real pivot came during clinical rotations. The breakthrough finally came when imaging and structural studies revealed that this protein was interacting

peptide variants The Galien Foundation Announces 2023 Prix Galien UK Award Candidates Exscientia Appoints Harvard

The biological validation came from Jean-Philippe Pin’s group at the Genomic Functional Institute in pHSense with other HTRF assays for multi-pathway mapping—G protein, arrestin, internalization—on the same To hear the full story of how pHSense came to life—and why the GLP-1 data changed everything— 🎧 Listen

.” — Tom Sakmar Enter the Toolkit As the pilot data came together, rotation student Ilana Kotliar  joined

The turning point came during her master’s program in pharmacogenomics. Industry experience gave her perspective, but purpose came from aligning research with urgent, real-world

Once the first images came in, the scientific questions multiplied: Could the probe support super-resolution That same emotional imprint hit with the whole-islet image. And the most striking validation came from in vivo GPCR imaging.

December 2021 "Dame Carol Robinson DBE, FRS, FRSC, FMedSci, Oxford University’s first female Professor

When I came this morning to work this is how I found my desk.

disciplined structure of industry science helped her re-find purpose and build confidence for what came I came away from that job with just a whole new appreciation for immunology and for pregnancy.

Learning from COVID-19 One striking example came from his COVID-19 work during his PhD.

While early evidence for the role of oligomerization in receptor signaling came from ensemble biochemical

Instead of testing one compound at a time, they evaluated multiple probes in the same experimental conditions — same transfection, same cells, same humidity, same everything. JB emphasizes how much of their progress came from staying open, asking questions freely, and engaging Many of the connections that shaped the probes’ development came from simple conversations that began Berlin — chemists, theorists, biochemists, toxicologists, and cell biologists — all working toward the same

You’re no longer tracking the same protein species—and that changes everything. Allosteric Binding Is a Different Game. Learn the Rules. ability to vote on or suggest future topics Access to a community of fellow scientists solving the same

modulators with built-in selectivity and context sensitivity Why GPCR Allosteric Thinking Changes the Game What If the Same Site Behaves Differently Depending on the Ligand? The same modulator might enhance  one probe and inhibit  another, at the same site .

Day That Changed Everything: The Endogenous Receptor “Aha” Eric’s second “aha” moment with pHSense came