Hen egg-white lysozyme (HEWL), a paradigmatic glycoside hydrolase (GH), is a retaining β-glycosidase catalysing the cleavage of β-glycosidic bonds found in the cell wall of Grampositive bacteria. Despite extensive research, the nature and role of substrate distortion in catalysis is still unclear. Here, MM and QM/MM modelling was performed on a HEWL trisaccharide (NAM-B-β(1→4)-NAG-C-β(1→4)-NAM-D) product complex to investigate distortion and reactivity of the NAM-D ring bound in the -1 site of the enzyme.