Targeting cadherins with colicins: Molecular docking and dynamics reveal disruptive potential in cancer metastasis.

This study investigates the molecular interactions between colicin A and colicin N with E-cadherin and N-cadherin-key adhesion molecules involved in cancer metastasis. Employing in silico approaches, including molecular docking using ClusPro and molecular dynamics (MD) simulations with Desmond, we evaluated the stability and binding affinities of colicin-cadherin complexes. Molecular docking results revealed favourable binding poses for both colicins, with colicin A exhibiting higher affinity than colicin N. MD simulations confirmed the stability of these interactions through root mean square deviation (RMSD) and fluctuation (RMSF) analyses, showing minimal structural perturbations throughout the simulation trajectory. Key interacting residues were identified: GLN101 and ARG201 for colicin A, and ASP90 and LYS75 for colicin N, contributing to specific protein-protein interactions. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations supported the formation of strong, energetically favourable complexes. Colicin A's interaction was characterized by a combination of electrostatic and van der Waals forces, whereas colicin N relied primarily on hydrophobic interactions. The findings suggest that colicin A and N can effectively bind to cadherins, potentially disrupting the epithelial-to-mesenchymal transition (EMT)-a crucial process in cancer cell dissemination. These insights support the therapeutic potential of colicin-based compounds as modulators of cadherin-mediated signalling in metastatic cancers. Our study contributes to the growing evidence of antimicrobial peptides as promising candidates for targeted cancer interventions, particularly by exploiting protein-protein interaction networks central to tumor progression.