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Title

 

 

 

 

Identification of EPAC (Exchange Protein Activated by cAMP) bioinformatically as a potential signalling biomarker in Cardiovascular Disease (CVD) and its molecular docking by a lead molecule 

Authors

Saranya Bala, Ravi Kant Pathak, Vachaspati Mishra*

 

Affiliation

Department of Biotechnology, Lovely Professional University, Delhi - Jalandhar G.T. Road (NH-1), Phagwara 144402, Punjab, India 

Email

vachaspatimishra@rediffmail.com; *Corresponding author

 

Article Type

Hypothesis

 

Date

Received April 25, 2011; Accepted May 07, 2011; Published May 26, 2011

 

Abstract

The present work delineates the combinatorial approach of firstly, creation of a centralized data-set comprising signalling proteins identified on the basis of altered expression, such as over-expression or repression of a set of signalling protein(s) leading to the cause of the disease, which is based on published reports screened through Pubmed and secondly, in the in silico creation of novel lead (drug) molecules and docking of identified signalling biomarkers using such drugs to investigate possibility of their future application in the model systems eventually. EPAC (Exchange Protein Activated by cAMP) emerges as a signalling biomarker in cases studied presently. Brefeldin, the known inhibitor of EPAC, though the mechanism yet unexplored, has been the molecule used as the pharmacophore for creation of lead drug molecule. Various modifications have been incorporated into the pharmacophore to increase the hydrophobic interactions for increasing the binding efficiency of the generated lead molecule. Side-chain modifications of the pharmacophore and refinement of data through firedock upon docking of EPAC with the modified pharmacophore yielded best results on the bases of atomic contact energy, van der Waal and partial electrostatic interactions as well as additional estimations of the binding free energy. Modifications of CH3 at C15 with COOH and H at C2 with OH in brefeldin showed the best docking results on the basis of protein-drug interaction parameters. The present work provides a clue in rational design of EPAC inhibitors which could be developed as drug lead in combating CVD.

 

Keywords

CVD, EPAC, Brefeldin, Pharmacophore, Inhibitors

 

Citation

Bala et al. Bioinformation 6(5): 176-178 (2011)

 

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.