ANTIBACTERIAL EFFECT OF EPSILON-POLYLYSINE (Ε-PL) AGAINST ENTEROCOCCUS FAECALIS DURING ENDODONTIC IRRIGATION: AN IN-SILICO

Epsilon‐polylysine (ε‐Pl) is a naturally occurring cationic homopolymer composed of 25–35 L‐lysine residues, whose unique bonding through ε‐amino and carboxyl groups endows it with a high density of positive charges. This intrinsic property underpins its broad-spectrum antimicrobial activity, making it a promising candidate for endodontic applications aimed at eradicating persistent pathogens such as Enterococcus faecalis. Computational studies employing the 6bsq receptor a model featuring an anionic and polar binding pocket analogous to bacterial membranes emonstrate that ε‐Pl engages in multiple non-covalent interactions, including strong hydrogen bonds, ionic attractions, and van der Waals contacts. Molecular docking revealed a moderate binding free energy (~–4.55 kcal/mol), while molecular dynamics simulations confirmed the stability of the ε‐Pl–receptor complex with low root-mean-square deviation values (~1.41 Å). These findings suggest that ε‐Pl can effectively bind to and destabilize negatively charged bacterial cell membranes through a “carpet‐like” mechanism, ultimately leading to cell lysis. In the context of endodontics, the resilient biofilms and robust cell envelopes of E. faecalis present significant treatment challenges. ε‐Pl ability to disrupt these structures supports its potential use as an irrigant or intracanal medicament to eliminate E. faecalis and improve root canal treatment outcomes. In addition, ε‐Pl exhibits favorable absorption, distribution, metabolism, and excretion ADME properties and a well-established safety profile, further underscoring its suitability for clinical applications. This integrated approach, combining theoretical modeling with experimental insights, provides a robust framework for the development of ε‐Pl-based strategies aimed at resolving persistent endodontic infections.