ABSTRACT Platelet-activating factor receptor
(PAFR) is a member of G-protein coupled receptor
(GPCR) superfamily. Understanding the regulation
mechanisms of PAFR by its agonists and antagonists
at the atomic level is essential for designing
PAFR antagonists as drug candidates for treating
PAF-mediated diseases. In this study, a 3D model of
PAFR was constructed by a hierarchical approach
integrating homology modeling, molecular docking
and molecular dynamics (MD) simulations. Based
on the 3D model, regulation mechanisms of PAFR
by agonists and antagonists were investigated via
three 8-ns MD simulations on the systems of apo-
PAFR, PAFR-PAF and PAFR-GB. The simulations
revealed that binding of PAF to PAFR triggers the
straightening process of the kinked helix VI, leading
to its activated state. In contrast, binding of GB
to PAFR locks PAFR in its inactive state.