Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes involved in protein 
biosynthesis in all living organisms and are an unexploited antibacterial 
targets, as many strains of bacteria have become resistant to all established 
classes of antibiotics. Therefore, the main aim of this study is to discover new 
lead molecules which would be useful as anti-bacterial compounds. Pharmacophore 
models were developed by using CATALYST HypoGen with a training set of 29 
diverse methionyl-tRNA synthetase (MetRS) inhibitors. The best quantitative 
pharmacophore hypothesis (Hypo1) obtained a correlation coefficient of 0.975, 
root mean square deviation (RMSD) of 0.55 and cost difference (null cost-total 
cost) of 70.32. This Hypo1 was validated by two methods, first by using 104 test 
set molecules which resulted a correlation of 0.926 between HypoGen estimated 
activities versus experimental activities and secondly by Cat-Scramble 
validation method. This validated pharmacophore model was further used for 
screening databases for discovery of new MetRS inhibitors. The new lead 
compounds were further analyzed for drug-like properties. Homology modeled 
structure of Staphylococcus aureus MetRS was built and molecular docking studies 
were performed with many inhibitors using the newly built protein structure. 
Finally, it was found that the new leads exhibited good estimated inhibitory 
activity, calculated binding properties similar to experimentally proven 
compounds and also favorable drug-like properties.