  Water molecules inside G-protein coupled receptor have recently been
spotlighted in a series of crystal structures. To decipher the dynamics and
functional roles of internal waters in GPCR activity, we studied
A$_{\text{2A}}$ adenosine receptor using $\mu$sec-molecular dynamics
simulations. Our study finds that the amount of water flux across the
transmembrane (TM) domain varies depending on the receptor state, and that the
water molecules of the TM channel in the active state flow three times slower
than those in the inactive state. Depending on the location in solvent-protein
interface as well as the receptor state, the average residence time of water in
each residue varies from $\sim\mathcal{O}(10^2)$ psec to
$\sim\mathcal{O}(10^2)$ nsec. Especially, water molecules, exhibiting ultraslow
relaxation ($\sim\mathcal{O}(10^2)$ nsec) in the active state, are found around
the microswitch residues that are considered activity hotspots for GPCR
function. A continuous allosteric network spanning the TM domain, arising from
water-mediated contacts, is unique in the active state, underscoring the
importance of slow waters in the GPCR activation.
