Molecular Docking and Dynamics of a Series of Aza-heterocyclic Compounds Against Effector Protein NleL

The gram-negative bacterium called Escherichia coli is part of the intestinal microbiota of humans and warm-blooded animals; for this reason, the most of its strains are harmless. However, the strain of this pathogen that produces Shiga toxins with serotype O157:H7 can cause serious illnesses such as acute bloody diarrhea, which in turn can lead to life-threatening hemolytic uremic syndrome, especially in young children and older adults with a case fatality rate of 3 to 5%. This strain is contracted due to the consumption of spoiled or contaminated food. According to several world health organizations, this bacterium has an incidence of 2.8 million cases per year. Therefore, the present study examined the inhibitory capacity of the effector protein Nlel of enterohemorrhagic E. coli (PDB ID: 3NAW) against a series of aza-heterocyclic derivatives. A theoretical protocol was applied, based on docking and molecular dynamics techniques. This approach yielded several key properties, including the affinity energy, the stability of the compound with respect to the protein (RMSD), the hydrogen bond interactions presented between each of the compounds and the protein, along with the production stage MD simulations. Subsequently, for those compounds with promising properties, the binding free energies were calculated using the MMGBSA method to obtain the interaction strength between each aza-heterocyclic compound and the protein. The results of this study have enabled the identification of compounds with the potential to inhibit the infectious strain under investigation. This finding contributes to our understanding of the protein in question and its potential defense mechanisms.