Fossepre, Mathieu

Laaksonen, Aatto

Leherte, Laurence

Vercauteren, Daniel

English

Recent releases of numerous G protein-coupled receptors crystalline structures created the opportunity for computational methods to widely explore their dynamics. Here, we study the biological implication of the intrinsic flexibility properties of µ opioid receptor (µOR). First, one performed classical all-atom (AA) Molecular Dynamics (MD) simulations of µOR in its apo-form. We highlighted that the various degrees of bendability of the α-helices present important consequences on the plasticity of the µOR binding site. Hence, this latter adopts a wide diversity of shape and volume, explaining why µOR interacts with very diverse ligands. Then, one introduces a new strategy for parameterizing purely mechanical but precise coarse-grained (CG) elastic network models (ENMs). Those CG ENMs reproduced in a high accurate way the flexibility properties of µOR as observed with the AA simulations. At last, ones uses network modularization to design multi-grained (MG) models. They represent a novel type of low resolution models, different in nature versus CG models as being true multi-resolution models, i.e., each MG grouping a different number of residues. The three parts of our work constitute an integrated hierarchical and multiscale approach for tackling the flexibility of µOR

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RESEARCH OUTPUTS / RÉSULTATS DE RECHERCHEAuthor(s) - Auteur(s) :Publication date - Date de publication :Permanent link - Permalien :Rights / License - Licence de droit d’auteur :Bibliothèque Universitaire Moretus PlantinInstitutional Repository - Research PortalDépôt Institutionnel - Portail de la Rechercheresearchportal.unamur.beIntrinsic Flexibility of the  Opioid Receptor through Multiscale Modelling Approaches -COMP403Vercauteren, Daniel; Fossepre, Mathieu; Leherte, Laurence; Laaksonen, AattoPublished in:Abstracts of the 255th Annual Meeting and Exposition of the American Chemical SocietyPublication date:2018Document VersionPublisher's PDF, also known as Version of recordLink to publicationCitation for pulished version (HARVARD):Vercauteren, D, Fossepre, M, Leherte, L & Laaksonen, A 2018, Intrinsic Flexibility of the  Opioid Receptorthrough Multiscale Modelling Approaches - COMP403. in Abstracts of the 255th Annual Meeting and Expositionof the American Chemical Society. ACS, 255th ACS National Meeting & Exposition, New Orleans, LA, UnitedStates, 18/03/18.General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.            • Users may download and print one copy of any publication from the public portal for the purpose of private study or research.            • You may not further distribute the material or use it for any profit-making activity or commercial gain            • You may freely distribute the URL identifying the publication in the public portal ?Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Download date: 23. Jun. 2020

Intrinsic Flexibility of the μ Opioid Receptor through Multiscale Modelling Approaches - COMP403

https://pure.unamur.be/ws/files/37009185/acs255_COMP403.pdf

Intrinsic Flexibility of the μ Opioid Receptor through Multiscale Modelling Approaches - COMP403

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