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OJBTM

Online Journal of Bioinformatics©

Volume 20(2):135-143, 2019.


In silico drug binding glycerol phosphate dehydrogenase-1 for treatment of Brugada syndrome. 

 

Senthil Raja, Raja Rajenderan Anbazhagan

 

Bioinformatics Division, Department of Zoology, Faculty of Science,  Annamalai University, India.

 

Raja S,  Anbazhagan RR., In silico drug binding glycerol phosphate dehydrogenase-1 for treatment of Brugada syndrome, Onl J Bioinform., 20(2):135-143, 2019. Brugada syndrome can be characterized by ECG ST segment elevation in right precordial leads (V1 to V3), in right bundle branch block, ventricular tachyarrhythmia and sudden cardiac death. Syncope at rest or during sleep is common and if tachycardia does not terminate it can lead to ventricular fibrillation and death. A mutation in Glycerol-3-phosphate dehydrogenase 1-like gene (GPD1L), an ion channel modulator in the heart, is linked to Brugada Syndrome inherited as autosomal dominant and more common in Asian males. Co-expression of A280V GPD1-L with SCN5A gene in HEK cells reduces inward Na+ currents ~50% to induce Brugada syndrome. We used a structure-based approach to identify a novel inhibitor anti-arrhythmic GPD1-L protein with atomic coordinates of small molecules through PubChem. Molecular docking based on Argus Lab combined with the large well-characterized database of small molecules, allowed for rapid turnaround time for molecular docking for top scoring compounds blocking GPD1-L protein. Propafenone exhibited high binding affinity to PHE 93 with low energy of 8.82743 Kcal/mol but free  -14.5097 kcal/mol.

 

Keywords: BrS, GPD1-L, ST segment, ion channel, ventricular fibrillation, SCN5A, HEK cell.


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