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

Research output: Contribution in Book/Catalog/Report/Conference proceedingConference contribution

Abstract

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.
LanguageEnglish
Title of host publicationAbstracts of the 255th Annual Meeting and Exposition of the American Chemical Society
PublisherACS
Publication statusPublished - 2018
Event255th ACS National Meeting & Exposition - New Orleans, LA, United States
Duration: 18 Mar 201822 Mar 2018

Meeting

Meeting255th ACS National Meeting & Exposition
CountryUnited States
CityNew Orleans, LA
Period18/03/1822/03/18

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flexibility
plastic properties
helices
atoms
simulation
molecular dynamics
proteins
ligands

Cite this

Vercauteren, D., Fossepre, M., Leherte, L., & Laaksonen, A. (2018). Intrinsic Flexibility of the μ Opioid Receptor through Multiscale Modelling Approaches - COMP403. In Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society ACS.
Vercauteren, Daniel ; Fossepre, Mathieu ; Leherte, Laurence ; Laaksonen, Aatto. / Intrinsic Flexibility of the μ Opioid Receptor through Multiscale Modelling Approaches - COMP403. Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society. ACS, 2018.
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title = "Intrinsic Flexibility of the μ Opioid Receptor through Multiscale Modelling Approaches - COMP403",
abstract = "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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booktitle = "Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society",
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Vercauteren, D, Fossepre, M, Leherte, L & Laaksonen, A 2018, Intrinsic Flexibility of the μ Opioid Receptor through Multiscale Modelling Approaches - COMP403. in Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society. ACS, 255th ACS National Meeting & Exposition, New Orleans, LA, United States, 18/03/18.

Intrinsic Flexibility of the μ Opioid Receptor through Multiscale Modelling Approaches - COMP403. / Vercauteren, Daniel; Fossepre, Mathieu; Leherte, Laurence; Laaksonen, Aatto.

Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society. ACS, 2018.

Research output: Contribution in Book/Catalog/Report/Conference proceedingConference contribution

TY - GEN

T1 - Intrinsic Flexibility of the μ Opioid Receptor through Multiscale Modelling Approaches - COMP403

AU - Vercauteren, Daniel

AU - Fossepre, Mathieu

AU - Leherte, Laurence

AU - Laaksonen, Aatto

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

M3 - Conference contribution

BT - Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society

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Vercauteren D, Fossepre M, Leherte L, Laaksonen A. Intrinsic Flexibility of the μ Opioid Receptor through Multiscale Modelling Approaches - COMP403. In Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society. ACS. 2018