作者
Heba Abdel‐Halim, Jane R Hanrahan, David E Hibbs, Graham AR Johnston, Mary Chebib
发表日期
2008/4
期刊
Chemical biology & drug design
卷号
71
期号
4
页码范围
306-327
出版商
Blackwell Publishing Ltd
简介
We modelled the N‐terminal ligand‐binding domain of the ρ1 GABAC receptor based on the Lymnaea stagnalis acetylcholine‐binding protein (L‐AChBP) crystal structure using comparative modelling and validated using flexible docking guided by known mutagenesis studies. A range of known ρ1 GABAC receptor ligands comprising seven full agonists, 10 partial agonists, 43 antagonists and 12 inactive molecules were used to evaluate and validate the models. Of the 50 models identified, six models that allowed flexible ligand docking in accordance with the experimental data were selected and used to study detailed receptor‐ligand interactions. The most refined model to accommodate all known active ligands featured a cavity comprising of a volume of 488 Å3. A detailed analysis of the interaction between the ρ1 GABAC receptor model and the docked ligands revealed possible H‐bonds and cation‐π …
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H Abdel‐Halim, JR Hanrahan, DE Hibbs… - Chemical biology & drug design, 2008