Bacterial resistance is a global public health problem because of the ineffectiveness of conventional antibiotics against super pathogens. To counter this situation, the search for or design of new molecules is essential to inhibit the key proteins involved in several stages of bacterial infection. One of these key proteins is DNA gyrase, which is responsible for packaging and unfolding of DNA chains during replication. Virtual screening calculations of 583,900 molecules against the ATPase site of DNA gyrase (PDB ID 7PQM) resulted in three promising molecules (Z927783420, Z4422201766, and Z2440107042) with significant binding modes at the active site, according to molecular docking studies. Additionally, they exhibited lower toxicological profiles than the previously reported 80S inhibitors. Molecular dynamics calculations revealed crucial interactions responsible for the inhibition process, with residues ASP87, GLU94, and ASN60 belonging to the ATPase site. On the other hand, the binding energy calculated using the MM/GBSA protocol highlighted Z2440107042 as the most promising inhibitor, with the best binding energy (-74.77 kcal/mol), suggesting that this molecule is a strong candidate for further biological studies.
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