Molecular simulations of hevein/(GlcNAc)3 complex with weakened OH/O and CH/π hydrogen bonds: implications for their role in complex stabilization

Carbohydrate-protein complexes are often characterized by interactions via aromatic amino acid residues. Several mechanisms have been proposed to explain these stacking-like interactions between pyranose sugars and aromatic moieties. The physical basis of these interactions is being explained as either dispersion CH/pi or hydrophobic. In order to elucidate the nature of these interactions, we performed a series of molecular dynamics simulation of hevein domain (HEV32) in complex with (beta-D-GlcNAc)(3). Selected OH/O and CH/pi hydrogen bonds involved in carbohydrate recognition were artificially weakened in 100 ns molecular dynamics simulations. Separate weakening of either OH/O or CH/pi hydrogen bonds was not sufficient to destabilize the complex. This indicates that other effects, not solely CH/pi dispersion interactions, contribute significantly to the stability of the complex. Significant destabilization of complexes was reached only by simultaneous weakening of OH/O and CH/pi hydrogen bonds. This also shows that classical hydrogen bonds and CH/pi interactions are working in concert to stabilize this carbohydrateeprotein test case. (C) 2015 Elsevier Ltd. All rights reserved.