Projects per year
To understand these properties, classical molecular dynamics (MD) simulations can provide numerous clarifications. Therein, we modelize a coarse-grained patch of a membrane with two phospholipids and µOR by NAMD (NAnoscale Molecular Dynamics) for 1 µs.
The two lipids considered to study the influence of the membrane rigidity on the µOR conformations are: DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholin) and an unsaturated one, POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin). More particularly, to study protein conformations, we examine the tilt of the seven transmembrane helices of µOR during the MD simulations for both types of membranes. As the DPPC is saturated, µOR is constrained in a rigid membrane and protein/lipid interactions are forced. The number of contacts between amino acids and lipids was calculated to highlight specific interaction sites for DPPC and POPC on the receptor. Our work demonstrates the crucial choice of lipids to perform MD by their impact on protein conformations .
Ultimately, our goal is to perform MD simulations with the most realistic lipid composition in order to guide docking experiments and explain the roles of lipids towards structural and functional properties of membrane proteins.
 Manglik A., Kruse A., Kobilka T., Thian F., Mathiesen J., Sunahara R., Pardo L., Weis W., Kobilka B., Granier S., Crystal structure of the mu-opioid receptor bound to a morphinan antagonist, Nature, 2012, 485: 321-7.
 Jastrzebska B., Debinski A., Filipek S., Palczewski K., Role of membrane integrity on G protein-coupled receptors: rhodopsin stability and function, Progress in Lipid Research, 2011, 50: 267-77.
 Shang Y., Filizola M., Opioid receptors: structural and mechanistic insight into pharmacology and signaling, European Journal of Pharmacology, 2015, doi: 10.1016.
 Angladon M.A., Fossépré M., Leherte L., Vercauteren, D. P., How POPC, DPPC, and POPE interact with the µ opioid receptor: a coarse-grained molecular dynamics answer, in preparation.
|Publication status||Published - 6 Nov 2015|
|Event||Understanding function of proteins in membrane by atomistic and multiscale simulations - CECAM USI-Lugano, Lugano, Switzerland|
Duration: 10 Nov 2015 → 12 Nov 2015
|Symposium||Understanding function of proteins in membrane by atomistic and multiscale simulations|
|Period||10/11/15 → 12/11/15|
Etude de l'influence de la membrane plasmique sur les propriétés structurales et fonctionnelles du récepteur opïoide µ
Angladon, M. & Vercauteren, D.
1/10/13 → 30/09/17
Marie-Ange Angladon (Poster)10 Nov 2015 → 12 Nov 2015
Activity: Participating in or organising an event types › Participation in conference