Investigation of plant antimicrobial peptides against selected pathogenic bacterial species using a peptide-protein docking approach

Antimicrobial resistance is the key threat to global health due to high morbidity and mortality. The alteration of bacterial proteins, enzymatic degradation, and change of membrane permeability towards antimicrobial agents are the key mechanisms of antimicrobial resistance. Based on the current condition, there is an urgent clinical need to develop new drugs to treat these bacterial infections. In the current study, the binding patterns of selected antimicrobial peptides (AMPs) with different multidrug-resistant bacterial strains have been analyzed. Among ten selected AMPs in this study, napin and snakin-1 exhibited the best scores and binding patterns. Napin exhibited strong interactions with penicillin-binding protein 1a of Acinetobacter baumannii (with a binding score of -158.7 kcal/mol and ten hydrogen bonds), with glucose-1-phosphate thymidylyltransferase of Mycobacterium tuberculosis H37Rv (with a binding score of -107.8 kcal/mol and twelve hydrogen bonds), and with streptomycin 3-adenylyltransferase protein of Salmonella enterica (with a binding score of -84.2 kcal/mol and four hydrogen bonds). Similarly, snakin-1 showed strong interactions with oxygen-insensitive NADPH nitroreductase of Helicobacter pylori (with a binding score of -105.0 kcal/mol and thirteen hydrogen bonds) and with penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus (with a binding score of -103.8 kcal/mol and twenty-three hydrogen bonds). The docking results were further validated by molecular dynamics simulations. The results of this computational approach support the evidence of efficiency of these AMPs as potent inhibitors of these specific proteins of bacterial strains. However, further validations are required to fully evaluate the potential of selected AMPs as drug candidates against these resistant bacterial strains.Peer reviewe

Molecular Docking and Simulation-Binding Analysis of Plant Phytochemicals with the Hepatocellular Carcinoma Targets Epidermal Growth Factor Receptor and Caspase-9

Among primary liver cancers, hepatocellular carcinoma (HCC) is one of the most common forms and it has been categorized as the joint-fourth largest reason of cancer-related deaths globally. Different factors such as alcohol abuse, hepatitis B and C, viral infections, and fatty liver diseases are mainly related to the pathogenesis of HCC. In the current study, 1000 total various plant phytochemicals were docked to proteins involved in HCC. The compounds were docked to the active site amino acids of epidermal growth factor receptor and caspase-9 as receptor proteins in order to explore their inhibiting potential. The top five compounds against each receptor protein were explored as potential drug candidates on the basis of their binding affinity and root-mean square deviation values. The top two compounds against each protein were found to be liquoric acid (S-score −9.8 kcal/mol) and madecassic acid (S-score −9.3 kcal/mol) against EGFR, and limonin (S-score −10.5 kcal/mol) and obamegine (S-score −9.3 kcal/mol) against the caspase-9 protein. The selected phytochemicals were further assessed through drug scanning using Lipinski’s rule of five to explore their molecular properties and druggability. According to the ADMET analysis, the selected phytochemicals were found to be non-toxic and non-carcinogenic. Finally, the molecular dynamics simulation study revealed that liquoric acid and limonin were stabilized within the binding pockets of EGFR and capase-9, respectively, and stayed firmly bound throughout the simulation. In light of the current findings, the phytochemicals reported in this study, especially liquoric acid and limonin, could be used as potential drugs for the treatment of HCC in the future