title: In silico inhibition of GABARAP activity using antiepileptic medicinal derived compounds.
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.
authors.affiliation: Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, KSA ; Authors contributed equally.
authors.forename: Shilu
authors.initials: S
authors.lastname: Mathew
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, KSA ; Authors contributed equally.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Faheem
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, KSA.
authors.forename: Abdulrahman L
authors.initials: AL
authors.lastname: Al-Malki
authors.affiliation: Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, KSA ; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, KSA.
authors.forename: Taha A
authors.initials: TA
authors.lastname: Kumosani
authors.affiliation: Medical Biotechnology and Translational Medicine Research, King Fahd Medical Research Center, King Abdul Aziz University, PO Box 80216 Jeddah 21589, Saudi Arabia.
authors.forename: Ishtiaq
authors.initials: I
authors.lastname: Qadri
keywords: Epilepsy; antiepileptic drugs; inhibitors; ligand; γ-amino butyric acid type-A receptor associated protein