Binding Difference of Fipronil with GABAARs in Fruitfly and Zebrafish: Insights from Homology Modeling, Docking, and Molecular Dynamics Simulation Studies

2014 ◽  
Vol 62 (44) ◽  
pp. 10646-10653 ◽  
Author(s):  
Nan Zheng ◽  
Jiagao Cheng ◽  
Wei Zhang ◽  
Weihua Li ◽  
Xusheng Shao ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Homology Modeling ◽  
Dynamics Simulation ◽  
Simulation Studies

scholarly journals Homology Modeling and Molecular Dynamics Simulation Studies of the human resistin protein

2009 ◽  
Vol 96 (3) ◽  
pp. 652a-653a
Author(s):  
Chilamakuri C. Sekhar Reddy ◽  
Ramanathan Sowdhamini ◽  
Bernard Offmann
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Homology Modeling ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Human Resistin

scholarly journals Homology Modeling and Molecular Dynamics Simulation Studies of an Inward Rectifier Potassium Channel

2000 ◽  
Vol 78 (6) ◽  
pp. 2929-2942 ◽  
Author(s):  
Charlotte E. Capener ◽  
Indira H. Shrivastava ◽  
Kishani M. Ranatunga ◽  
Lucy R. Forrest ◽  
Graham R. Smith ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Homology Modeling ◽  
Potassium Channel ◽  
Inward Rectifier ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Inward Rectifier Potassium Channel ◽  
Rectifier Potassium Channel

scholarly journals Computational Investigations on the Binding Mode of Ligands for the Cannabinoid-Activated G Protein-Coupled Receptor GPR18

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 686 ◽  
Author(s):  
Alexander Neumann ◽  
Viktor Engel ◽  
Andhika B. Mahardhika ◽  
Clara T. Schoeder ◽  
Vigneshwaran Namasivayam ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
G Protein ◽  
Phenyl Ring ◽  
Binding Mode ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Binding Modes ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

GPR18 is an orphan G protein-coupled receptor (GPCR) expressed in cells of the immune system. It is activated by the cannabinoid receptor (CB) agonist ∆9-tetrahydrocannabinol (THC). Several further lipids have been proposed to act as GPR18 agonists, but these results still require unambiguous confirmation. In the present study, we constructed a homology model of the human GPR18 based on an ensemble of three GPCR crystal structures to investigate the binding modes of the agonist THC and the recently reported antagonists which feature an imidazothiazinone core to which a (substituted) phenyl ring is connected via a lipophilic linker. Docking and molecular dynamics simulation studies were performed. As a result, a hydrophobic binding pocket is predicted to accommodate the imidazothiazinone core, while the terminal phenyl ring projects towards an aromatic pocket. Hydrophobic interaction of Cys251 with substituents on the phenyl ring could explain the high potency of the most potent derivatives. Molecular dynamics simulation studies suggest that the binding of imidazothiazinone antagonists stabilizes transmembrane regions TM1, TM6 and TM7 of the receptor through a salt bridge between Asp118 and Lys133. The agonist THC is presumed to bind differently to GPR18 than to the distantly related CB receptors. This study provides insights into the binding mode of GPR18 agonists and antagonists which will facilitate future drug design for this promising potential drug target.

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