Multiple templates-based homology modeling enhances structure quality of AT1 receptor: validation by molecular dynamics and antagonist docking

被引:0
作者
Pandian Sokkar
Shylajanaciyar Mohandass
Murugesan Ramachandran
机构
[1] Madurai Kamaraj University,School of Chemistry
[2] Madurai Kamaraj University,School of Biological Sciences
来源
Journal of Molecular Modeling | 2011年 / 17卷
关键词
AT1 receptor; Explicit membrane; Homology modeling; I-TASSER; Molecular docking; Molecular dynamics; Multiple templates;
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学科分类号
摘要
We present a comparative account on 3D-structures of human type-1 receptor (AT1) for angiotensin II (AngII), modeled using three different methodologies. AngII activates a wide spectrum of signaling responses via the AT1 receptor that mediates physiological control of blood pressure and diverse pathological actions in cardiovascular, renal, and other cell types. Availability of 3D-model of AT1 receptor would significantly enhance the development of new drugs for cardiovascular diseases. However, templates of AT1 receptor with low sequence similarity increase the complexity in straightforward homology modeling, and hence there is a need to evaluate different modeling methodologies in order to use the models for sensitive applications such as rational drug design. Three models were generated for AT1 receptor by, (1) homology modeling with bovine rhodopsin as template, (2) homology modeling with multiple templates and (3) threading using I-TASSER web server. Molecular dynamics (MD) simulation (15 ns) of models in explicit membrane-water system, Ramachandran plot analysis and molecular docking with antagonists led to the conclusion that multiple template-based homology modeling outweighs other methodologies for AT1 modeling.
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页码:1565 / 1577
页数:12
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