Carbohydrate–protein recognition probed by density functional theory and ab initio calculations including dispersive interactions

Carbohydrate–protein recognition has been studied by electronic structure calculations of complexes of fucose and glucose with toluene, p-hydroxytoluene and 3-methylindole, the latter aromatic molecules being analogues of phenylalanine, tyrosine and tryptophan, respectively. We use mainly a density functional theory model with empirical corrections for the dispersion interactions (DFT-D), this method being validated by comparison with a limited number of high level ab initio calculations. We have calculated both binding energies of the complexes as well as their harmonic vibrational frequencies and proton NMR chemical shifts. We find a range of minimum energy structures in which the aromatic group can bind to either of the two faces of the carbohydrate, the binding being dominated by a combination of OH–π and CH–π dispersive interactions. For the fucose–toluene and α-methyl glucose–toluene complexes, the most stable structures involve OH–π interactions, which are reflected in a red shift of the corresponding O–H stretching frequency, in good quantitative agreement with experimental data. For those structures where CH–π interactions are found we predict a corresponding blue shift in the C–H frequency, which parallels the predicted proton NMR shift. We find that the interactions involving 3-methylindole are somewhat greater than those for toluene and p-hydroxytoluene.