Evaluation of molecular modeling of agonist binding in light of the crystallographic structure of an agonist-bound A₂A adenosine receptor.

ABSTRACT: Molecular modeling of agonist binding to the human A(2A) adenosine receptor (AR) was assessed and extended in light of crystallographic structures. Heterocyclic adenine nitrogens of cocrystallized agonist overlaid corresponding positions of the heterocyclic base of a bound triazolotriazine antagonist, and ribose moiety was coordinated in a hydrophilic region, as previously predicted based on modeling using the inactive receptor. Automatic agonist docking of 20 known potent nucleoside agonists to agonist-bound A(2A)AR crystallographic structures predicted new stabilizing protein interactions to provide a structural basis for previous empirical structure activity relationships consistent with previous mutagenesis results. We predicted binding of novel C2 terminal amino acid conjugates of A(2

SUBMITTER: Deflorian F 

PROVIDER: S-EPMC3261785 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature