Projects per year
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.
|Title of host publication||Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society|
|Publication status||Published - 2018|
|Event||255th ACS National Meeting & Exposition - New Orleans, LA, United States|
Duration: 18 Mar 2018 → 22 Mar 2018
|Meeting||255th ACS National Meeting & Exposition|
|City||New Orleans, LA|
|Period||18/03/18 → 22/03/18|
Activities per year
21 Mar 2018
Activity: Talk or presentation types › Invited talk
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.