Binding profile of protein-ligand inhibitor complex and structure based design of new potent compounds via computer-aided virtual screening.

Abstract Background Mycobacterium tuberculosis protein target (DNA gyrase) is a type II topoisomerase target present in all bacteria. The enzyme comprises of two subunits A and B. DNA binding domain is located in the subunits A while the catalysis and cleavage of two DNA strands occur in the subunits B using ATP hydrolysis. This enzyme has been reported to emerge in extensively drug resistant tuberculosis. Therefore this research aimed to design new potent compounds against the target and establish the analysis of protein–ligand binding interaction between the target and novel quinoline analogues via the application of in silico virtual screening to predict the inhibition binding affinities of the analogues. Result The docking results revealed that compound ID 17 with efficient inhibition activity has a noticeable binding affinity of −18.8 kcal/mol. Hence compound 17 was designated as the reference template to design novel fourteen compounds with higher binding affinities as a promising compounds. Conclusion Designed compound 17i, 17j and 17n with lead binding affinities among the designed compounds were observed with the most perceptible binding affinity which ranges from (−21.2 to −26.8) kcal/mol compared to low binding affinity (-5.8 kcal/mol) computed for ethambutol.