Exploration of CH⋯π mediated stacking interactions in saccharide: aromatic residue complexes through conformational sampling

Saccharides interact with aromatic residues mostly through CH⋯π mediated stacking interactions. The energetics of such interactions depends upon the mutual Position-orientations (POs) of the two moieties. The POs found in the crystal structures are only a subset of the various possible ways of interaction. Hence, potential energy surfaces of saccharide-aromatic residue complexes have been explored by mixed Monte Carlo multiple minimum/low mode sampling. The saccharides considered in this study are α/β-D-glucose, β-D-galactose, α-D-mannose, and α/β-L-fucose. p-Hydroxytoluene, toluene and 3-methylindole were used as analogs of tyrosine, phenylalanine and tryptophan, respectively. The saccharides interact from either above or below the π-cloud of an aromatic ring but not along the edges. The POs preferred by different saccharides, both in the preferred chair and skew-boat forms, for interacting with different aromatic amino acid residue analogs have been identified. Aromatic residues can interact with the same –CH group in many POs but not so with the –OH groups. Changes in the configurations of pyranose ring carbon atoms cause remarkable changes in stacking preferences. β-D-Galactose and β-L-fructose interact only through their b- and a-faces, respectively. Saccharides use a wide variety of apolar patches for stacking against aromatic residues and these have been analyzed in detail. As many as four –CH groups can simultaneously participate in CH⋯π interactions, especially with 3-methylindole owing to its larger surface area