Academic Journal
Nicotinic receptors: From protein allostery to computational neuropharmacology
| العنوان: | Nicotinic receptors: From protein allostery to computational neuropharmacology |
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| المؤلفون: | Cecchini, Marco, Changeux, Jean-Pierre |
| المساهمون: | Institut de Chimie de Strasbourg (IC), Université de Strasbourg (UNISTRA)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS), Récepteurs Canaux - Channel Receptors, Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Récepteurs-Canaux, Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS), Kavli Institute for Brain and Mind San Diego, University of California San Diego (UC San Diego), University of California (UC)-University of California (UC), Collège de France (CdF (institution)), This project has received funding from the European Union's Horizon 2020 Framework Programme for Research and Innovation under Specific Grant Agreement No. 945539 (Human Brain Project SGA3). This work received funding from the French National Research Agency (ANR-18-CE11-0015)., ANR-18-CE11-0015,PENTA_CONTROL,Étude de la dynamique structurale d'un canal ionique pentamérique pour la conception rationnelle des médicaments(2018), European Project: 945539,H2020,H2020-SGA-FETFLAG-HBP-2019,HBP SGA3(2020) |
| المصدر: | ISSN: 0098-2997. |
| بيانات النشر: | CCSD Elsevier |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | MWC theory, Allosteric regulation, Synaptic receptors, Nicotinic acetylcholine receptor, Neuropharmacology, Brain disease, Thermodynamic modeling, Potency, Efficacy, Selectivity, Modeling, Molecular dynamics, Binding affinity calculations, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; We propose an extension and further development of the Monod-Wyman-Changeux model for allosteric transi- tions of regulatory proteins to brain communications and specifically to neurotransmitters receptors, with the nicotinic acetylcholine receptor (nAChR) as a model of ligand-gated ion channels. The present development of- fers an expression of the change of the gating isomerization constant caused by pharmacological ligand binding in terms of its value in the absence of ligands and several “modulation factors”, which vary with orthosteric lig- and binding (agonists/antagonists), allosteric ligand binding (positive allosteric modulators/negative allosteric modulators) and receptor desensitization. The new – explicit – formulation of such “modulation factors”, pro- vides expressions for the pharmacological attributes of potency, efficacy, and selectivity for the modulatory lig- ands (including endogenous neurotransmitters) in terms of their binding affinity for the active, resting, and de- sensitized states of the receptor. The current formulation provides ways to design neuroactive compounds with a controlled pharmacological profile, opening the field of computational neuro-pharmacology. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/34656371; info:eu-repo/grantAgreement//945539/EU/Human Brain Project Specific Grant Agreement 3/HBP SGA3; PUBMED: 34656371 |
| DOI: | 10.1016/j.mam.2021.101044 |
| الاتاحة: | https://pasteur.hal.science/pasteur-03576129 https://pasteur.hal.science/pasteur-03576129v1/document https://pasteur.hal.science/pasteur-03576129v1/file/S0098299721001047.pdf https://doi.org/10.1016/j.mam.2021.101044 |
| Rights: | http://creativecommons.org/licenses/by-nc/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.31A6E33D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.mam.2021.101044 |
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