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

•The physical nature of interactions stabilizing carbohydrate–protein complexes is not fully understood•Weakening of CH/π or OH/O hydrogen bonds does not break a model complex in a simulation•Simultaneous weakening of both types of hydrogen bonds was necessary to break the complex•Dispersion CH/π interactions are not the only interactions stabilizing the tested hevein–sugar complex.

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/π 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 (β-d-GlcNAc)3. Selected OH/O and CH/π hydrogen bonds involved in carbohydrate recognition were artificially weakened in 100 ns molecular dynamics simulations. Separate weakening of either OH/O or CH/π hydrogen bonds was not sufficient to destabilize the complex. This indicates that other effects, not solely CH/π 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/π hydrogen bonds. This also shows that classical hydrogen bonds and CH/π interactions are working in concert to stabilize this carbohydrate–protein test case.

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