Molecular pharmacophore selectivity studies, virtual screening, and in silico ADMET analysis of GPCR antagonists
作者： Hany Emary Ali Ahmed , Mohamed F Zayed , Saleh Ihmaid , None
DOI: 10.1007/S00044-015-1389-6
关键词: Molecular descriptor 、 G protein-coupled receptor 、 5-HT2A receptor 、 In silico 、 Virtual screening 、 Drug discovery 、 Pharmacophore 、 Chemistry 、 Combinatorial chemistry 、 Rational design
摘要: The G protein-coupled receptors (GPCRs), especially amine type, comprise the largest family of proteins targeted by drug discovery. One major hurdles in design safe and effective drugs targeting GPCRs is finding ligands that are highly selective for a specific receptor subtype. To gain insights into structural basis ligand subtype selectivity within (D1, D2, D3, D4, Alpha1, 5HT1a, 5HT2a), we generated 3D pharmacophore models all seven subtypes. performance molecular descriptors rational to maximize GPCR antagonists with different profile investigated this publication. Different family- target-specific were built applied searching evaluate their identifying target-selective hits. Five prediction obtained as potential hits using virtual screening protocol ZINC database. This study multiple mapping provided deep insight subtype-selectivity determinants can be used novel tool discovery potent which could treatment GPCR-linked diseases.
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