Structure-based virtual screening, free energy of binding and molecular dynamics simulations to propose novel inhibitors of Mtb-MurB oxidoreductase enzyme.

Currently, the growing incidence of drug resistance toward tuberculosis intensified the need for discovery of novel targets and their inhibitors. The enzyme MurB which is involved in one of the steps for peptidoglycan biosynthesis is an effective target that can produce drugs having lesser side-effects. Recently the only crystal structure of Mycobacterium Tuberculosis MurB has been deposited and, therefore, in the present study, we have used this as a target for virtual screening of drug-like molecules from the ZINC Database. We have also designed a complete workflow for the process which resulted in 12 hit compounds that have good docking scores, ΔGbind, and Glide energy. The hits obtained have also been found to share structural features with some known antibiotics such as Amoxicillin. Furthermore, MD simulations on the top most hit L1 displayed its stable binding with the enzyme. Thus, this study has proved helpful in proposing novel inhibitors for MurB enzyme that can be tested against various TB strains.