Homology modeling, binding site identification and docking study of human angiotensin II type I (Ang II-AT₁) receptor

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• 作者：Vivek K. Vyas ; ^{vicky_1744@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Manjunath Ghate ; Kinjal Patel ; Gulamnizami Qureshi ; Surmil Shah
• 关键词：Angiotensin II ; AT1 receptor ; Homology modeling ; Molecular docking ; ARBs
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：74
• 期：Complete
• 页码：42-48
• 全文大小：1789 K

文摘

Ang II-AT₁ receptors play an important role in mediating virtually all of the physiological actions of Ang II. Several drugs (SARTANs) are available, which can block the AT₁ receptor effectively and lower the blood pressure in the patients with hypertension. Currently, there is no experimental Ang II-AT₁ structure available; therefore, in this study we modeled Ang II-AT₁ receptor structure using homology modeling followed by identification and characterization of binding sites and thereby assessing druggability of the receptor. Homology models were constructed using MODELLER and I-TASSER server, refined and validated using PROCHECK in which 96.9% of 318 residues were present in the favoured regions of the Ramachandran plots. Various Ang II-AT₁ receptor antagonist drugs are available in the market as antihypertensive drug, so we have performed docking study with the binding site prediction algorithms to predict different binding pockets on the modeled proteins. The identification of 3D structures and binding sites for various known drugs will guide us for the structure-based drug design of novel compounds as Ang II-AT₁ receptor antagonists for the treatment of hypertension.