Origin of the metabolic site selectivity of 7,12-dimethylbenz[ a ]anthracene catalysed by the P450 1B1 cytochrome: an in silico protocol

) in two modes. The π-π interactions formed by Phe231 and Phe268 with DMBA constituted a "sandwich" structure, which acted as a critical stabilizing element in both modes. In both modes, DMBA was metabolized by an electrophilic addition-rearrangement mechanism. Notably, C3 was the electrophilic addition site in mode I, while in mode II, the extra amide-π interaction between Gly329 and DMBA made C4 the preferred metabolic site. Consequently, in path II, the electrophilic addition-rearrangement metabolic process at the C4 site in mode II became the relatively favored metabolic pathway. These results provide theoretical insights into the biological metabolic processes of DMBA and contribute to the comprehension of its toxification potential and cancer risks.