Activation of G-protein-coupled receptors is thermodynamically linked to lipid solvation.

ABSTRACT: Preferential lipid solvation of the G-protein-coupled A_2A adenosine receptor (A_2AR) is evaluated from 35 μs 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 G-protein-coupled receptor 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 A_2AR's first solvation she

SUBMITTER: Leonard AN 

PROVIDER: S-EPMC8204388 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature