Computational Approaches to Elucidate the Mechanism of Serine–Threonine Kinase (AKT1) Inhibition by Streptococcus pyogenes Exotoxin Superantigen‐Derived Peptides: Pioneering Cancer Therapy

Abstract

ABSTRACTA serine–threonine kinase 1 (AKT1) plays a significant role in biological processes, including cell division, survival, glucose metabolism, and apoptosis pathway. It interacts with numerous growth factors and external stimuli, and numerous types of human cancer have been associated with its activation. Bacterial toxins have the potential to eradicate tumors and can be utilized for producing bacterial‐based cancer vaccines. One of the few bacterial species recognized for producing superantigen exotoxins is Streptococcus pyogenes. Superantigen produced by S. pyogenes, exotoxins such as SPEA, SPEB, and SPEC, which activate CD4+ cells and cause the release of cytokines. This study aims to explore various computational methods for inhibiting AKT1 using exotoxin peptides from S. pyogenes, specifically SPEA, SPEB, and SPEC. Identified peptides were analyzed for allergencity, toxicity, hemolytic, physicochemical, and anticancer potential using computational tools The peptides were modeled using PEP‐FOLD and validated with Ramachandran plot analysis using the Procheck server. Protein–peptide docking was conducted using HDOCK, followed by an analysis of the binding free energies of the complexes. Molecular dynamics simulations were employed to investigate structural changes within AKT1‐peptide complexes. Results indicate that the identified anticancer peptide demonstrates strong binding affinities and favorable interaction profiles with AKT1. The stability observed throughout simulations suggests potential anticancer effects mediated through these peptide complexes.