Local Enrichment of Unsaturated Chains Around the A2A Adenosine Receptor.

Abstract

Two 15 μsec all-atom simulations of the A2A adenosine receptor were obtained in a ternary mixture of cholesterol, saturated, and unsaturated phosphatidyl choline lipids. An analysis of local lipid solvation is reported on the basis of a Voronoi tessellation of the upper and lower leaflets, identifying first and second solvation shells. The local environment of both the inactive state and the partially active state of the receptor are significantly enriched in unsaturated chains but depleted in cholesterol and saturated chains, relative to the bulk membrane composition. In spite of the local depletion of cholesterol, the partially active receptor binds cholesterol at three locations during the entire simulation trajectory. These long-lived interactions represent the extreme of a very broad distribution of first solvation shell lipid lifetimes, confounding sharp distinctions between lipid interactions. The broad distribution of lifetimes also make equilibrating the local lipid environment difficult, necessitating long simulation times.