The relationship between the deamidation mechanism and the catalytic activity of triosephoshate isomerase has been studied with a QM/MM method where AM1/AMBER parametrization was used. The mechanism considered in this study is compared to that previously described for a dipeptide model in vacuum using density functional theory. The present study focuses on determining whether the ligand-induced deamidation proceeds via an intrasubunit or intersubunit transmission of the conformational change. Our calculations have shown that, although the binding of the substrate has an effect on the conformational preferences of asparagine 15 on the same subunit, deamidation takes place on the juxtaposed subunit.