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.
|titre||Abstracts of the 255th Annual Meeting and Exposition of the American Chemical Society|
|Etat de la publication||Publié - 2018|
|Evénement||255th ACS National Meeting & Exposition - New Orleans, LA, États-Unis|
Durée: 18 mars 2018 → 22 mars 2018
|Réunion||255th ACS National Meeting & Exposition|
|La ville||New Orleans, LA|
|période||18/03/18 → 22/03/18|