title: Molecular mechanism of action for reversible P2Y12 antagonists.
abstract: Recently, reversible antagonists of the P2Y(12) receptor have been reported. However, the mechanisms of binding have not been elucidated. To this end, a number of homology models were built by means of three programs from four templates. A consensus model was derived from those initial models. The final model was created by refining the consensus model with molecular dynamics simulations. The agonist and antagonists of P2Y(12) have been docked in the final model. For the agonist, the Arg256, Lys280, and Phe252 are "hot" residues. For the antagonists, the Lys280 and Phe252 are "hot" residues that have hydrogen bonding contacts and π-π interactions, respectively. These results can explain the observations of mutation experiments and can guide the design of new inhibitors.
authors: Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100194, PR China.
authors: Haibo
authors: H
authors: Liu
authors: Hu
authors: H
authors: Ge
authors: Yong
authors: Y
authors: Peng
authors: Peigen
authors: P
authors: Xiao
authors: Jun
authors: J
authors: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D058912:Purinergic P2Y Receptor Agonists / Q000737:chemistry / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D058925:Receptors, Purinergic P2Y12 / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: C548576:P2RY12 protein, human; D058912:Purinergic P2Y Receptor Agonists; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12