Journal of Computer-Aided Molecular Design

, Volume 19, Issue 12, pp 887–901 | Cite as

Modelling of carbohydrate–aromatic interactions: ab initio energetics and force field performance

  • Vojtěch SpiwokEmail author
  • Petra Lipovová
  • Tereza Skálová
  • Eva Vondráčková
  • Jan Dohnálek
  • Jindřich Hašek
  • Blanka Králová


Aromatic amino acid residues are often present in carbohydrate-binding sites of proteins. These binding sites are characterized by a placement of a carbohydrate moiety in a stacking orientation to an aromatic ring. This arrangement is an example of CH/π interactions. Ab initio interaction energies for 20 carbohydrate–aromatic complexes taken from 6 selected ultra-high resolution X-ray structures of glycosidases and carbohydrate-binding proteins were calculated. All interaction energies of a pyranose moiety with a side chain of an aromatic residue were calculated as attractive with interaction energy ranging from −2.8 to −12.3 kcal/mol as calculated at the MP2/6-311+G(d) level. Strong attractive interactions were observed for a wide range of orientations of carbohydrate and aromatic ring as present in selected X-ray structures. The most attractive interaction was associated with apparent combination of CH/π interactions and classical H-bonds. The failure of Hartree–Fock method (interaction energies from +1.0 to −6.9 kcal/mol) can be explained by a dispersion nature of a majority of the studied complexes. We also present a comparison of interaction energies calculated at the MP2 level with those calculated using molecular mechanics force fields (OPLS, GROMOS, CSFF/CHARMM, CHEAT/CHARMM, Glycam/AMBER, MM2 and MM3). For a majority of force fields there was a strong correlation with MP2 values. RMSD between MP2 and force field values were 1.0 for CSFF/CHARMM, 1.2 for Glycam/AMBER, 1.2 for GROMOS, 1.3 for MM3, 1.4 for MM2, 1.5 for OPLS and to 2.3 for CHEAT/CHARMM (in kcal/mol). These results show that molecular mechanics approximates interaction energies very well and support an application of molecular mechanics methods in the area of glycochemistry and glycobiology.


ab initio carbohydrate recognition C–H/π interactions force field glycobiology glycosidases lectins 



assisted model building with energy refinement


Becke–Slater-HF 3-term exchange and Lee–Yang–Parr correlation hybrid functional


basis set superposition error


carbohydrate-binding module


complete basis set


coupled cluster with single, double and perturbative triple excitation


chemistry at Harvard molecular mechanics


carbohydrate hydroxyl groups represented by extended atoms


carbohydrate solution force field


density functional theory


Groningen molecular simulation




molecular mechanics version 2


molecular mechanics version 3


Møller–Plesset perturbation theory; second order


optimized potentials for liquid simulations


protein data bank


root mean square deviation


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Authors would like to gratefully acknowledge the Czech Science Foundation (GACR 204/02/0843) and the Academy of Sciences of the Czech Republic (projects B500500512 and AVOZ 40500505) for financial support.


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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Vojtěch Spiwok
    • 1
    Email author
  • Petra Lipovová
    • 1
  • Tereza Skálová
    • 2
  • Eva Vondráčková
    • 2
  • Jan Dohnálek
    • 2
  • Jindřich Hašek
    • 2
  • Blanka Králová
    • 1
  1. 1.Department of BiochemistryInstitute of Chemical Technology in PraguePrague 6Czech Republic
  2. 2.Institute of Macromolecular ChemistryAcademy of Sciences of the Czech RepublicPraha 6Czech Republic

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