Molecular Interactions of Purinoceptor Subtype (P2Y12) with its Agonist Adenosine Diphosphate - An in silico Approach

Abstract

The P2Y12 receptor is a member of the family of rhodopsin like G-protein coupled receptors (GPCRs) and represents an interesting new therapeutical target since it is involved in the platelet aggregation and the disorders related to thrombosis. In order to shed light on the molecular basis of the interactions of the P2Y12 with its agonists, the interactions of receptor and the ligands were examined by molecular modeling methods. The 3D models of the P2Y12 receptor were constructed by using homology-modeling method using the crystal structure of bovine rhodopsin as template. Among the modeled structures, the one with appropriate stereochemical quality was selected by using PROCHECK. The docking software HEX 4.0 was used to dock the natural ligand, adenosine diphosphate (ADP) into the model of P2Y12.The amino acid residue Thr-264 of P2Y12 model served as an important residue for nonbonded interaction with ADP.