Homology modeling, active site prediction, and targeting the anti hypertension activity through molecular docking on endothelin

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Title	Homology modeling, active site prediction, and targeting the anti hypertension activity through molecular docking on endothelin – B receptor domain
Authors	Daddam Jayasimha Rayalu¹*, Chandrabose Selvaraj², Sanjeev Kumar Singh², Ramakrishan Ganeshan³, Nagapatla Udaya Kumar¹ & Panthangi Seshapani⁴
Affiliation	¹Department of Bioinformatics, Global Institute of Biotechnology, 3-6-276/2, Himayat Nagar, Hyderabad-29, Andhra Pradesh, India; ²Computer Aided Drug Design and Molecular Modeling Laboratory, Department of Bioinformatics, Alagappa University, Karaikudi-630003, Tamilnadu, India; ³Department of Microbiology, P.K.N arts and science college, P.K.N. Nagar, Vidathakulam Road, Tirumangalam -625 706; ⁴Department of Microbiology, Sri Venkateswara University, Tirupati - 517 502, Andhra Pradesh, India.
Email	jaimscbiotech2007@gmail.com; *Corresponding author
Article Type	Hypothesis
Date	Received January 04, 2012; Accepted January 07, 2012; Published 20, 2012
Abstract	In cardiovascular system, activation of Endothelin receptors causes vasoconstriction which leads to Pulmonary Arterial Hypertension (PAH). Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension. Bosentan is intended to affect vasoconstriction, hypertrophic and fibrotic effects by blocking the actions of receptors ETA and ETB. In this study we identified the action of Bosentan on endothelin B receptor using docking studies with homology modeled endothelin B receptor. Through the modeled protein, the flexible Docking study was performed with Bosentan and its derivatives with theoretically predicted active sites. The results indicated that amino acid ARG82, ARG84 and HIS197 present in endothelin B receptor are core important for binding activities and these residues are having strong hydrogen bond interactions with Bosentan. We have investigated the Bosentan and its derivatives interactions and scoring parameters using gold docking package. Among the docked compounds, one of the Bosentan derivatives BD6 shows better interaction than Bosentan with endothelin B receptor. Our results may be helpful for further investigations in both in vivo and in vitro conditions.
Keywords	Bosentan; Endothelin receptors; Modeller7v7; Molecular docking; Pulmonary Arterial Hypertension.
Citation	*Rayalu et al.* Bioinformation 8(2): 081-086 (2012)
Edited by	P Kangueane
ISSN	0973-2063
Publisher	Biomedical Informatics
License	This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.