[en] Highlights: • The error bypass itinerary is revealed by QM/MM method. • The phosphoryl transfer step was found to be rate-determining. • Asp126 and Lys207 are important in suppressing the error bypass. • Glu127 facilitates the error bypass process. • Protein environment influence the error bypass barrier. The error bypass mechanism of DNA polymerase ι toward N-(deoxyguanosin-8-yl)-1-aminopyrene adduction was studied by using quantum mechanics/molecular mechanics method. The most favorable mechanism highlights three elementary steps: proton transfer from dC to dATP, phosphoryl transfer, and deprotonation of dAMP. The phosphoryl transfer step was found to be rate-determining. The calculated average barrier (23.8 kcal mol⁻¹) is in accordance with the experimental value (21.5 kcal mol⁻¹). Electrostatic influence analysis indicates that residues Asp126 and Lys207 significantly suppress the error bypass while Glu127 facilitates the process. These results highlight the origins of the mutagenicity of nitrated polycyclic aromatic hydrocarbons in molecular detail.