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Title |
In silico inhibition of GABARAP activity using antiepileptic medicinal derived compounds |
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Authors |
Shilu Mathew1†, Muhammad Faheem2†, Abdulrahman L Al-Malki2, Taha A Kumosani2, 3 & Ishtiaq Qadri4* |
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Affiliation |
1Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, KSA; 2Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, KSA; 3Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, KSA; 4Medical Biotechnology and Translational Medicine Research, King Fahd Medical Research Center, King Abdul Aziz University, PO Box 80216 Jeddah 21589, Saudi Arabia
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ishtiaq80262@yahoo.com; *Corresponding author
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Article Type |
Hypothesis
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Date |
Received February 21, 2015; Accepted March 14, 2015; Published April 30, 2015
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Abstract |
Epilepsy is a neurological disorder affecting more than 50 million people worldwide. It can be controlled by antiepileptic drugs (AEDs) but more than 30% patients are still resistant to AEDs. To overcome this problem, researchers are trying to develop novel approaches to treat epilepsy including the use of herbal medicines. The γ-amino butyric acid type-A receptor associated protein (GABARAP) is ubiquitin-like modifier implicated in the intracellular trafficking of GABAAR. An in silico mutation was created at 116 amino acid position G116A, and an in silico study was carried out to identify the potential binding inhibitors (with antiepileptic properties) against the active sites of GABARAP. Five different plant derived compounds namely (a) Aconitine (b) Berberine (c) Montanine (d) Raubasine (e) Safranal were selected, and their quantitative structure-activity relationships (QSAR) have been conducted to search the inhibitory activity of the selected compounds. The results have shown maximum number of hydrogen bond (H-bond) interactions of Raubasine with highest interaction energy among all of the five compounds. So, Raubasine could be the best fit ligand of GABARAP but in vitro, and in vivo studies are necessary for further confirmation.
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Keywords |
Epilepsy, antiepileptic drugs, γ-amino butyric acid type-A receptor associated protein, inhibitors, ligand.
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Citation |
Mathew et al.
Bioinformation 11(4): 189-195 (2015) |
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Edited by |
P Kangueane
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ISSN |
0973-2063
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Publisher |
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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. |