"Activity of G-protein coupled receptor is thermodynamically linked to lipid solvation" with Alison Leonard, Postdoctoral Fellow at University of Delaware (Online Seminar)

Title: Activity of G-protein coupled receptor is thermodynamically linked to lipid solvation

Speaker: Alison Leonard, Postdoctoral Fellow at University of Delaware

Hosted by: Jeffery Klauda

Abstract: 

Preferential lipid solvation of the G-protein coupled A2A adenosine receptor (A2AR) is evaluated from 35 sec of all-atom molecular dynamics simulation. A coarse-grained transition matrix algorithm is developed to overcome slow equilibration of the first solvation shell, obtaining estimates of the free energy of solvation by different lipids for the receptor in different activation states. Results indicate preference for solvation by unsaturated chains, which favors the active receptor. A model for lipid-dependent GPCR activity is proposed in which the chemical potential of lipids in the bulk membrane modulates receptor activity. The entropies associated with moving saturated and unsaturated lipids from bulk to A2AR's first solvation shell are evaluated. Overall, the acyl chains are more disordered (i.e., obtain a favorable entropic contribution) when partitioning to the receptor surface, and this effect is augmented for the saturated chains which are relatively more ordered in bulk.  

Seminars start at 4:00 pm and refreshments served at 3:45 pm. All seminars are held in the Conference Room (1116) of the Institute for Physical Science and Technology (IPST) Building, unless otherwise noted.