To date, several Glucosyltransferase C (GtfC) inhibitors have been identified and experimentally validated. All these inhibitors have been validated at different experimental conditions like degree of purity, animal models, kinetic conditions, experimental environment etc.; and most of these inhibitors (ligands) proved to be quite effective in their respective validation environment. However, due to varied experimental validation conditions, and absence of molecular interaction data, there is no way to prioritize these validated ligands for their inhibition potential against GtfC. The present study is a novel attempt of comparative evaluation of the interaction of the validated ligands on a single platform and under similar conditions with a dual objective, i.e. ligand prioritization for their respective inhibitory potential and elucidation of the involved unknown molecular interactions. Carbohydrate derivatives (6-Deoxy sucrose and Trichloro-galactosucrose) were identified as the most promising GtfC inhibitors. In addition, Asp588, Trp517, and Asn481 amino acid residues of the domain A1 proved vital for the inhibitory effect. The study highlights the importance of the comparative analysis of the validated ligands in order to identify the most promising leads for drug discovery against dental caries.
Keywords: D-acarbose; Glycosyltransferase C; Streptococcus mutans; biofilm; prioritization; quantum mechanical.