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Understanding the regulation mechanisms of PAF receptor by agonists and antagonists: Molecular modeling and molecular dynamics simulation studies
Author(s) -
Gui Chunshan,
Zhu Weiliang,
Chen Gang,
Luo Xiaomin,
Liew Oi W.,
Puah Chum M.,
Chen Kaixian,
Jiang Hualiang
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21213
Subject(s) - platelet activating factor receptor , homology modeling , molecular dynamics , molecular model , platelet activating factor , chemistry , g protein coupled receptor , receptor , docking (animal) , microbiology and biotechnology , computational biology , biophysics , biology , antagonist , stereochemistry , biochemistry , medicine , immunology , enzyme , computational chemistry , nursing
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. Proteins 2007. © 2007 Wiley‐Liss, Inc.