Identification of a Different Agonist-Binding Site and Activation Mechanism of the Human P2Y₁ Receptor.

ABSTRACT: The human P2Y₁ receptor (P2Y₁R) is a purinergic G-protein-coupled receptor (GPCR) that functions as a receptor for adenosine 5'-diphosphate (ADP). An antagonist of P2Y₁R might potentially have antithrombotic effects, whereas agonists might serve as antidiabetic agents. On the basis of the antagonist-bound MRS2500-P2Y₁R crystal structure, we constructed computational models of apo-P2Y₁R and the agonist-receptor complex 2MeSADP-P2Y₁R. We then performed conventional molecular dynamics (cMD) and accelerated molecular dynamics (aMD) simulations to study the conformational dynamics after binding with agonist/antagonist as well as the P2Y₁R activation mechanism. We identified a new agonist-binding site of P2Y₁

SUBMITTER: Li Y 

PROVIDER: S-EPMC5653743 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature