De-Novo Design of Hits Against New Delhi Metallo-β-Lactamase Enzyme

The New Delhi Metallo-β-lactamase 1 (NDM-1) is a class of Metallo-β lactamase enzyme. It is responsible for hydrolyzing almost all β-lactam antibiotics, leading to multi-drug resistance in bacteria. The lack of specific therapeutic options against this target creates an emerging need to develop new molecules against it. The multistep fragment- and knowledge-based de-novo design methods were considered for this study to design small molecules. The designed molecules were evaluated by molecular docking and dynamics simulation, followed by drug-likeness prediction. This study reports that a new drug-like chemical entity exhibits good binding behavior against the MDM-1 enzyme. Nonetheless, in-depth biological evaluation is required to determine the efficacy of the designed binders to develop new therapeutics against NDM-1.