MP2/6-311++G(d,p) study on galactose–aromatic residue analog complexes in different position-orientations of the saccharide relative to aromatic residue

Abstract

Presence of an aromatic amino acid facing the non-polar surface of galactopyranose has been found to be a common feature of the saccharide-binding site in galactose-specific lectins. Only a few studies have addressed the energetics of saccharide–aromatic residue interactions so far. Interactions between saccharides and aromatic amino acids depend on both the position as well as the orientation of the saccharide relative to the aromatic residue. This makes the systematic scanning of the energy surface nearly impossible, since an infinite number of position-orientation combinations are theoretically possible. In view of this, position-orientations that have been observed for saccharides in their complexes with proteins have been taken to characterize the interactions between galactose and aromatic amino acid residues. In this study, single point energy calculations on galactose–aromatic residue analog complexes at MP2/6-311G++ ∗∗ level of theory has been performed on 43 position-orientations. It is found that the interaction energies in various position-orientations are negative and thus stabilizing and are comparable to that of a hydrogen bond. The interaction energies of the saccharide with the three aromatic residue analogs 3-methylindole (for Trp), toluene (for Phe) and p-hydroxyltoluene (for Tyr) are comparable to each other. Qualitative rationalizations of the observed interaction energies in these complexes and the influence/importance of position-orientations have also been discussed elaborately in the present study.