BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Memento EPFL// BEGIN:VEVENT SUMMARY:G protein-coupled receptors functional dynamics revealed by experi mental and computational structural data DTSTART;VALUE=DATE:20261007 DTSTAMP:20260501T024518Z UID:ec72d6c5fc497777ab50e572766c4b21da3df62e525193d253dfff81 CATEGORIES:Conferences - Seminars DESCRIPTION:You can apply to participate and find all the relevant informa tion (speakers\, abstracts\, program\,...) on the event website: https:// www.cecam.org/workshop-details/g-protein-coupled-receptors-functional-dyna mics-revealed-by-experimental-and-computational-structural-data-1488.\n\nR egistration is required to attend the full event\, take part in the social activities and present a poster at the poster session (if any).  However \, the EPFL community is welcome to attend specific lectures without registration if the topic is of interest to their research. Do not hesitat e to contact the CECAM Event Manager if you have any question.\n\nDescri ption\n\nG protein-coupled receptors (GPCRs) represent a vast and diverse class of transmembrane proteins that orchestrate a wide range of physiolog ical processes by responding to both endogenous and exogenous ligands [1\, 2]. These receptors are essential to critical functions such as metabolism \, immune regulation\, neuronal signaling\, and sensory perception - inclu ding vision and olfaction. Due to their physiological relevance and membra ne accessibility\, GPCRs are the targets of approximately 34% of all presc ribed medications\, accounting for nearly 27% of the global pharmaceutical market [3]. \nDespite their pharmaceutical importance\, key aspects of G PCR function remain elusive. The canonical activation model posits that ag onist binding to the extracellular orthosteric site triggers allosteric ch anges - most notably\, the outward displacement of transmembrane helices 5 (TM5) and 6 (TM6) on the intracellular side - ultimately leading to recep tor activation [2-4]. However\, recent evidence suggests a more nuanced me chanism. In several GPCRs\, activation appears to involve cooperative enga gement between the agonist and the G protein. For example\, the G protein may disrupt an "inactivating ionic lock" - a salt bridge between TM3 and T M6 - while the agonist stabilizes the active conformation. In some recepto rs\, this is complemented by the formation of an “activating ionic lock ” between TM5 and TM6 [5-8]. These dual contributions are considered the rmodynamically essential for full activation [7].\nAdding further complexi ty\, GPCR activity is regulated by conformational microswitches and finely tuned intra-protein interaction networks. These dynamic rearrangements ar e difficult to capture and often elude direct correlation with functional outcomes. Moreover\, allosteric ligands - which bind sites distinct from t he orthosteric pocket - are being increasingly identified [9-12]\, along w ith small molecules capable of biased signaling\, i.e.\, preferential acti vation of specific intracellular pathways [11-13\, 16\, 17]. These finding s reveal a rich and underexplored conformational landscape that governs GP CR signaling. In addition\, native membrane components—such as lipids an d interacting proteins\, including GPCR oligomers—are known to significa ntly modulate receptor function [11\, 18-22].\nTo disentangle these intric acies\, computational modeling has become indispensable\, offering atomist ic insight into GPCR conformational dynamics and mechanistic understanding [1-2\, 7\, 11\, 14\, 16–21\, 23]. Nevertheless\, key questions remain - particularly regarding the structural basis of biased signaling\, strateg ies for leveraging allosteric networks in pharmacology\, and the modulator y role of the lipid environment. Addressing these gaps is crucial for both fundamental biology and the rational design of next-generation GPCR-targe ting drugs with improved selectivity and safety profiles. \nThese scienti fic challenges form the foundation of our upcoming workshop\, which will f ocus on the latest experimental and computational approaches for studying the functional dynamics of GPCRs. Given the profound health\, economic\, a nd societal implications of modulating these receptors with precision\, we aim to strengthen the interdisciplinary nature of the event by increasing the representation of experimental research and integrating cutting-edge artificial intelligence applications into the program.\nBuilding upon the success of the 2022 and 2024 editions - which led to new collaborations an d a landmark publication in Nature Reviews Drug Discovery [24] - our goa l is to further enhance communication and collaboration between experiment alists and theoreticians. The workshop will serve as a reference point for young scientists and students\, offering a platform to interact with lead ing international experts. We are confident that this initiative will fost er insightful discussions and contribute meaningfully to advancing the fie ld of GPCR pharmacology.\n\nReferences\n\n[1] J. Smith\, R. Lefkowitz\, S. Rajagopal\, Nat. Rev. Drug. Discov.\, 17\, 243-260 (2018)\n[2] P. 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Christopoulos\, Nature\, 559\, 45-53 (2018)\n[16] L. Slosky\, M. Caron\, L. Barak\, Trend s in Pharmacological Sciences\, 42\, 283-299 (2021)\n[17] C. Zhu\, X. Lan \, Z. Wei\, J. Yu\, J. Zhang\, Acta Pharmaceutica Sinica B\, 14\, 67-86 ( 2024)\n[18] V. D’Amore\, P. Conflitti\, L. Marinelli\, V. Limongelli\, C hem\, 10\, 3678-3698 (2024)\n[19] A. Mafi\, S. Kim\, W. Goddard\, Nat. Ch em.\, 15\, 1127-1137 (2023)\n[20] H. Batebi\, G. Pérez-Hernández\, S. R ahman\, B. Lan\, A. Kamprad\, M. Shi\, D. Speck\, J. Tiemann\, R. Guixà-G onzález\, F. Reinhardt\, P. Stadler\, M. Papasergi-Scott\, G. Skiniotis\, P. Scheerer\, B. Kobilka\, J. Mathiesen\, X. Liu\, P. Hildebrand\, Nat. S truct. Mol. Biol.\, 31\, 1692-1701 (2024)\n[21] A. Manglik\, T. Kim\, M. Masureel\, C. Altenbach\, Z. Yang\, D. Hilger\, M. Lerch\, T. Kobilka\, F. Thian\, W. Hubbell\, R. Prosser\, B. Kobilka\, Cell\, 161\, 1101-1111 (2 015)\n[22] M. Congreve\, C. de Graaf\, N. Swain\, C. Tate\, Cell\, 181\, 81-91 (2020)\n[23] J. Lorente\, A. Sokolov\, G. Ferguson\, H. Schiöth\, A . Hauser\, D. Gloriam\, Nat. Rev. Drug. Discov.\, 24\, 458-479 (2025)\n[2 4] M. Lopez‐Balastegui\, T. Stepniewski\, M. Kogut‐Günthel\, A. Di Pi zio\, M. Rosenkilde\, J. Mao\, J. Selent\, British. J. Pharmacology.\, 18 2\, 3211-3224 (2024)\n  LOCATION:Aula Magna\, USI Lugano https://www.desk.usi.ch/en/lugano-campus- map-access-facilities STATUS:CONFIRMED END:VEVENT END:VCALENDAR