Molecular mechanism of action for reversible P2Y12 antagonists

► A homology model for P2Y12 receptor was created based on a consensus approach following with molecular dynamics simulations. ► The mechanisms of binding for the reversible antagonists of the P2Y12 receptor are elucidated. ► For the agonist, the Arg256, Lys280, and Phe252 were found as “hot” residues. ► For the antagonists, the Lys280 and Phe252 had hydrogen bonding contacts and π-π interactions.