Structure based drug design of 4-aminoquinilone derivatives in DNA Gyrase B subunit for anti-tuberculosis agents using molecular dynamics simulations

Mycobacterial DNA gyrase B subunit, GyrB has been identified to be one of the potentially underexploited drug targets in the field of antitubercular drug discovery. 4-aminoquinoline derivatives were developed as potential GyrB inhibitors. In the present study, we applied molecular dynamics simulations to elucidate the binding mode and the key interactions of 4aminoquinoline derivatives in the GyrB pocket. The obtained results indicated that the crucial interactions of the highest active compound were hydrogen bond interactions with Met93(A) and electrostatic interactions of carboxylic group with Arg185(B) sidechain in the GyrB pocket. This interaction absented in other compounds. Moreover, hydrophobic interactions are also important for binding affinities in GyrB binding site of 4aminoquinoline derivatives. Therefore, the obtained results from this study provide informative structural concept for designing of novel 4-aminoquinoline derivatives with better potency of GyrB inhibitors against Mycobacterial tuberculosis.