Exploring G-protein coupled receptor activation with multiscale molecular simulations

by Stefano Vanni (EPF-Lausanne, Switzerland)

Monday 24 Oct 2011, 16:00 → 17:00 Europe/Rome

Aula Conversi (Dip. di Fisica - Edificio G. Marconi)

G protein coupled receptors (GPCRs) are a large family of integral membrane proteins involved in many signal transduction pathways. Recently crystallized structures of several GPCRs have opened new avenues for the understanding of the molecular mechanisms of action of GPCRs, but they also generated some controversy on the proposed mechanism of GPCR activation. To understand the molecular details of GPCR activation, we carried out submicrosecond classical molecular dynamics simulations of beta adrenergic receptors and of the rhodopsin dimer in explicit lipid bilayer under physiological conditions, together with multiscale QM/MM molecular dynamics simulations. Our results reconcile structural and biophysical experiments concerning GPCR activation while suggesting a molecular origin of this complex mechanism at atomic resolution.