Affinity chromatography with protein A from Staphylococcus aureus (SpA) is the 
most widespread and accepted methodology for antibody capture during the 
downstream process of antibody manufacturing. A triazine based ligand (ligand 
22/8) was previously developed as an inexpensive and robust alternative to SpA 
chromatography (Li et al. and Teng et al.). Despite the experimental success, 
there is no structural information on the binding modes of ligand 22/8 to 
antibodies, namely to Immunoglobulin G (IgG) molecules and fragments. In this 
work, we addressed this issue by a molecular docking approach allied to 
molecular dynamics simulations. Theoretical results confirmed the preference of 
the synthetic ligand to bind IgG through the binding site found in the 
crystallographic structure of the natural complex between SpA and the Fc 
fragment of IgG. Our studies also suggested other unknown "hot-spots" for 
specific binding of the affinity ligand at the hinge between V(H) and C(H)1 
domains of Fab fragment. The best docking poses were further analysed by 
molecular dynamics studies at three different protonation states (pH 3, 7 and 
11). The main interactions between ligand 22/8 and the IgG fragments found at pH 
7 were weaker at pH 3 and pH 11 and in these conditions the ligand start losing 
tight contact with the binding site, corroborating the experimental evidence for 
protein elution from the chromatographic adsorbents at these pH conditions.