Molecular Modeling of Structures and Interaction of Short Peptides and Sortase Family Protein of Enterococcus Faecalis: Basis for Developing Peptide-Based Therapeutics Against Multidrug Resistant Strains

The Enterococcus faecalis (E. faecalis) infection starts with initial adhesion to a host cell or abiotic surface by multiple adhesions on its cell membrane. The pathogenicity is due to virulence factors SrtA, SrtC, EbpA, EbpB, EbpC, and Aggregation Substance. E. faecalis developed resistance to the majority of standard therapies. Additionally, a notable key feature of E. faecalis is its ability to form biofilm in vivo. E. faecalis strains show resistance to aminoglycosides and β-lactam antibiotics with different degree of susceptibility. Sortases (SrtA and SrtC) are enzymes spatially localized at the septal region in majority of gram-positive bacteria during the cell cycle, which in-turn plays an important role in proper assembling of adhesive surface proteins and pilus on cell membrane. The studies have also proved that the both SrtA and SrtC were focally localized in E. faecalis and essential for efficient bacterial colonization and biofilm formation on the host tissue surfaces Using homology modeling and protein-peptide flexible docking methods, we report here the detailed interaction between peptides and EfSrt (Q836L7) enzyme. Plausible binding modes between EfSrt and the selected short biofilm active peptides were revealed from protein-peptide flexible docking. The simulation data further revealed critical residues at the complex interface and provided more details about the interactions between the peptides and EfSrt. The flexible docking simulations showed that the peptide-EfSrt binding was achieved through hydrogen bonding, hydrophobic, and van der Waals interaction. The strength of interactions between peptide-EfSrt complexes were calculated using standard energy calculations involving non-bonded interactions like electrostatic, van der Waals, and hydrogen bonds.