Insight into the screening of potential beta-lactamase inhibitors as anti-bacterial chemical agents through pharmacoinformatics study

Drug resistance is an unsolved and major concern in the bacterial infection. Continuous development of drug-resistance to the antibiotics exponentially rises the danger of bacterial infections. Chemical components from the plants are becoming a major resource of potentially effective therapeutic chemical agents for the wide range of diseases including bacterial infections. In the current study, pharmacoinformatics methodologies were implemented on more than two hundred known phytochemicals to find promising beta-lactamase inhibitors for therapeutically effective anti-bacterial agents. Initially, the molecular docking-based score was used to reduce the chemical space of the selected dataset. Fourteen molecules were found to have more affinity towards the beta-lactamase in compared to the well-known anti-bacterial agent, Avibactam. Binding interactions analysis revealed the strong binding interactions between phytochemicals and catalytic amino residues. For further analysis, molecular dynamics (MD) simulations, density functional theory (DFT) and in silico pharmacokinetics studies were performed. Parameters from MD simulations studies suggested that selected molecules are strong enough to retain in the active site in different orientations of the beta-lactamase. The orbital energies obtained from the DFT study was undoubtedly explained the potentiality of the selected compounds for being effective beta-lactamase inhibitors. The drug-likeness and acceptable pharmacokinetics parameters were observed using in silico ADME analysis. Therefore, observations from the multiple pharmacoinformatics approach explained without any doubt that selected molecules are potential enough being promising anti-bacterial compounds.