Molecular Docking with Trehalose-6 Phosphate Phosphatase: A Potential Drug Target of Filaral Parasite ‘Brugia malayi’

Lakshminarayanan      Karthik; Palayam      Malathy; Annie      Trinitta; Krishnasamy      Gunasekaran

Abstract

Lymphatic Filariasis is a dreadful disease of mankind that infects more than one billion people worldwide. It is mainly caused by the nematode worms Wuchereria bancrofti, Brugia malayi and Brugia timori. Antifilarial agents that can kill all the stages in the life cycle of causative filariae are yet to be developed. Trehalose phosphatase is one of the key enzymes that plays a vital role in trehalose metabolism important for egg hatching of the Brugia malayi nematode. Interestingly, absence of similar protein in human makes this enzyme a potential drug target. As the structure of this enzyme has not been experimentally determined, a 3-Dimensional model of the target was generated by remote homology modeling. Since the magnesium ion is required for the structural integrity and enzymatic activity of the target protein, predicted model was therefore complexed with magnesium and docking studies were carried out. The lead compounds which competitively bind to this class of alpha-glucosidase family of enzymes, and thereby inhibit their activity were selected. With the generated model, an induced fit docking study was performed using Schrodinger supported GLIDE. The docking results indicated the conserved residues to be involved in antagonist binding and that the lead compounds could be used in designing anti-filarial drugs.

Keywords: Brugia malayi, GLIDE Docking, Glucosidase inhibitors, Homology Modeling, Lymphatic Filariasis, Trehalose-6 Phosphate Phosphatase, Filariasis, Tropical diseases, Thread like parasitic round worms, Parasitic Diseases, Disfiguring swelling of the legs, Genital organs, Elephantiasis, Lymph node, Inflammed