Getting insights of molecular interactions for potential drug candidates against S. aureus: Pharmacophore modeling, molecular screening and docking studies

Abstract

There are a vast number of newly synthesized drugs against various pathogens in the last few decades but the problem still remains intact due to unempirical approaches to synthesize molecules without proper study on the target. This study focusses on development of a pharmacophore model through incorporating features from a wide variety of azole-based scaffolds (183 numbers) and thereby molecular screening from online available databases and libraries (10,89,394 molecules). Out of them, 6,04,696 molecules are filtered out through the pharmacophore-based virtual screening. These best discovered molecules are then docked against the target S. aureus DNA gyrase followed by interaction analysis and ADME as well as MM-GBSA studies, which led us to 23 best-hit compounds. After in silico analysis, best 10 molecules were predicted which exhibited excellent binding affinity as well as interactions against the target protein and some are even better than the well-known drug, ciprofloxacin. This study enables us to excavate pre-existing molecules, which have not been explored till date against this pathogenic strain of bacteria, but can definitely be used as alternatives to resistant drugs.