KCS

Aminoacyl-tRNA synthetases (aaRSs) is one such target which are essential enzymes involved in protein biosynthesis. Inhibition of Methionyl-tRNA Synthetase (MetRS) is an effective way in control of bacterial growth as it has not been previously targeted by antibiotics. Therefore, main aim of this study is to discover new lead molecules which act as anti-bacterial agents by latest analogue based method of pharmacophore model generation by using CATALYST Hypogen program. A training set of 29 different MetRS inhibitors which have IC50 values ranging from 3.3 nM to 47400 nM were selected from an in-house database of 595 compounds. The best quantitative pharmacophore hypothesis consists of one hydrogen bond donor (HD), one hydrophobic aliphatic (HY-ALI) and two ring aromatic (RA) features with correlation coefficient of 0.975 and RMS deviation of 0.55. This validated pharmacophore model was further used for screening databases for discovery of new MetRS inhibitors. The new leads were further analyzed for drug like properties and also binding properties by docking study to make sure that they have all the properties of an ideal drug molecule.