Best poster prize for NARILIS PhD student Marie-Ange Angladon at the Doctoral Interdisciplinary Training School 2016
From May 17 to 19, Marie-Ange Angladon took part to the Doctoral Interdisciplinary Training School at the UNamur, and presented her research work during the poster session. Her poster entitled “Comparison of coarse-grain and all-atom methods for the study of the μ opioid receptor” was awarded with the prize from the academic jury and doctoral student jury.
ABSTRACT
Comparison of coarse-grain and all-atom methods for the study of the μ opioid receptor
M.-A. Angladon, L. Leherte, D. P. Vercauteren
Laboratoire de Physico-Chimie Informatique (PCI), Namedic center, Narilis Institute, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium
Opioid receptor, whose structure was revealed in 2012, are part of the G-protein coupled receptor (GPCRs), target of 50 % of drugs on the market today [1]. The structural and functional properties of transmembrane proteins are affected by the lipid environment [2]. To understand these processes, classical molecular dynamics (MD) simulations can provide numerous
clarifications. We compare the results of CG (coarsegrained, 1 μs) and AA (all-atom, 17 ns) simulations for a patch of membranes with POPC (1-palmitoyl-2-oleoyl-sn-glycero 3-phosphocholin) including the μ receptor using NAMD (NAnoscale Molecular Dynamic). CG simulations are quick but less accurate than AA simulations. We need them to demonstrate the role of lipids in μ conformations changes. For details and evidences, AA simulations are necessary.
Firstly, we examine the adaptation of the lipids to the receptor and vice versa. To do so, we determine precisely the interactions between the amino acids and lipids by calculating the distance between each other and the tilt of the helices of the μ protein during the MD simulation. Then, we study, via POCASA, the possible pockets at the surface of the protein to accomodate lipids and determine differents key conformations through clustering of the pockets.
Ultimately, our goal is to perform MD simulations with the most realistic lipid composition, the simplest and most significant in terms of protein/lipid interactions, in order to guide further docking experiments and show the importance of the various interactions of the protein with a lipid towards its structural and functional properties.
Bibliography:
[1] Manglik A., Kruse A, Kobilka T., Thian E, Mathiesen J., Sunahara R., Pardo L., Weis W., Kobilka B., Granier S. (2012) Crystal structure of the mu-opioid receptor bound to a morphinan
antagonist Nature 485: 321-7
[2] Jastrzebska B., Debinski A, Filipek S., Palczewski K. (2011) Role of membrane integrity on G protein-coupled receptors: rhodopsin stability and function Progress in Lipid Research 50: 267-77
M.-A. A. is grateful to the Fund for Scientific Research (F.R.S.-FNRS) for her doctoral position. This research used resources of the «Plateforme Technologique de Calcul Intensif (PTCI)» located at the University of Namur, Belgium, which is supported by the F.R.S.-FNRS. PTCI is a member of the «Consortium des Equipements de Calcul Intensif (CÉCI)».