biostudies-literatureUnknown11(6)Lal KDeoxynivalenol (DON) is a trichothecene mycotoxin from Fusarium species that contaminates cereal grains, posing health risks. DON binds to site A of the 60S ribosomal subunit in eukaryotes, triggering a ribotoxic stress response. Despite structural similarity, its metabolites, deepoxy-deoxynivalenol (DOM-1) and 3-epi-deoxynivalenol (3-epi-DON), are nontoxic, but the molecular basis of this difference is unclear. This study employed molecular docking, molecular dynamics (MD) simulations, and quantum chemical calculations based on Symmetry-Adapted Perturbation Theory (SAPT) to analyze the interactions of DON and its metabolites with the ribosomal site. Our results reveal that DON adopts a unique binding conformation, enabling strong and stable interactions with an Mg<supACS omega9575-9586https://www.ebi.ac.uk/biostudies/studies/S-EPMC12917688biostudies-literatureMolecular Dynamics and Quantum Chemical Insights into the Molecular Basis of Differential Toxicity of the Mycotoxin Deoxynivalenol (DON) and Its Microbial Derivatives DOM‑1 and 3-epi-DON.PMC12917688Oswald IPStigliani JLMirey GJolibois FVignard JLal KfalseMolecular Dynamics and Quantum Chemical Insights into the Molecular Basis of Differential Toxicity of the Mycotoxin Deoxynivalenol (DON) and Its Microbial Derivatives DOM‑1 and 3-epi-DON.Deoxynivalenol (DON) is a trichothecene mycotoxin from Fusarium species that contaminates cereal grains, posing health risks. DON binds to site A of the 60S ribosomal subunit in eukaryotes, triggering a ribotoxic stress response. Despite structural similarity, its metabolites, deepoxy-deoxynivalenol (DOM-1) and 3-epi-deoxynivalenol (3-epi-DON), are nontoxic, but the molecular basis of this difference is unclear. This study employed molecular docking, molecular dynamics (MD) simulations, and quantum chemical calculations based on Symmetry-Adapted Perturbation Theory (SAPT) to analyze the interactions of DON and its metabolites with the ribosomal site. Our results reveal that DON adopts a unique binding conformation, enabling strong and stable interactions with an Mg<sup2026-01-01T00:00:00Z2026 Feb2026-07-16T17:59:16.553Z2026-07-09T11:10:20.238ZS-EPMC129176884172673110.1021/acsomega.5c09756