Homology modeling, binding site identification and docking study of human angiotensin II type I (Ang II-AT1) receptor.
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.
Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382 481, Gujarat, India. Electronic address: vicky_1744@yahoo.com.
Vivek K
VK
Vyas
Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382 481, Gujarat, India.
Manjunath
M
Ghate
Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382 481, Gujarat, India.
Kinjal
K
Patel
Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382 481, Gujarat, India.
Gulamnizami
G
Qureshi
Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382 481, Gujarat, India.
Surmil
S
Shah
D000465:Algorithms; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1
ARBs; AT(1) receptor; Angiotensin II; Homology modeling; Molecular docking