Membrane Environment Modulates Ligand-Binding Propensity of P2Y12 Receptor.

ABSTRACT: The binding of natural ligands and synthetic drugs to the P2Y12 receptor is of great interest because of its crucial role in platelets activation and the therapy of arterial thrombosis. Up to now, all computational studies of P2Y12 concentrated on the available crystal structures, while the role of intrinsic protein dynamics and the membrane environment in the functioning of P2Y12 was not clear. In this work, we performed all-atom molecular dynamics simulations of the full-length P2Y₁₂ receptor in three different membrane environments and in two possible conformations derived from available crystal structures. The binding of ticagrelor, its two major metabolites, adenosine diphosphate (ADP) and 2-Methylthioadenosine diphosphate (2MeS-ADP) as agonist, and ethyl 6-[4-(benzylsulfon

SUBMITTER: Haghighi F 

PROVIDER: S-EPMC8069422 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature