Broadening the scope of bacteria DNA Gyrase B Inhibitors by marine compounds: Insights form molecular docking, MM-GBSA, molecular dynamics simulations and ADMET predictions

Abstract

• A library of marine compounds was screened against DNA gyrase using HTVS, SP, and XP docking. • Three top compounds had a good binding affinity with better docking scores. • MM-GBSA results revealed that these compounds had favorable binding free energy values. • MD simulations suggested interaction stability of selected compounds with the DNA gyrase. • These compounds showed acceptable ADMET properties and could be a promising lead antibacterial candidates. New antibacterial drugs are urgently needed to tackle the rapid rise in multi-drug-resistant bacteria. DNA gyrase B is a validated target for the development of new antibacterial drugs. The marine environment has proven to be a very rich source of diverse natural products with significant biological activities. Thus, in the present investigation, a library of marine natural compounds was screened against the active site of DNA gyrase B using multistage virtual screening using HTVS, SP, and XP docking modes of Glide. Notably, compounds CMNPD25880, CMNPD28952 and CMNPD28578 were found to have a good binding affinity against E. coli gyrase with docking scores values of -11.084, -10.809, and -10.699 Kcal/mol, respectively, in comparison with the bound ligand (docking score -9.899 kcal/mol). The MM-GBSA (Molecular Mechanics Generalized Born Surface Area) results revealed that these compounds had favorable binding free energy values comparable to that of the reference. Further, these three compounds were subjected to MD simulations, resulting in low RMSD values suggesting their interaction stability with the DNA gyrase binding site. Finally, the three compounds showed acceptable ADMET properties. Therefore, these marine-derived compounds could be a promising lead as antibacterial candidates which merit further future experimental testing.