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

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Summary

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.

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Abbreviations

AMBER:

assisted model building with energy refinement

B3LYP:

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

BSSE:

basis set superposition error

CBM:

carbohydrate-binding module

CBS:

complete basis set

CCSD(T):

coupled cluster with single, double and perturbative triple excitation

CHARMM:

chemistry at Harvard molecular mechanics

CHEAT:

carbohydrate hydroxyl groups represented by extended atoms

CSFF:

carbohydrate solution force field

DFT:

density functional theory

GROMOS:

Groningen molecular simulation

HF:

Hartree–Fock␣method

MM2:

molecular mechanics version 2

MM3:

molecular mechanics version 3

MP2:

Møller–Plesset perturbation theory; second order

OPLS:

optimized potentials for liquid simulations

PDB:

protein data bank

RMSD:

root mean square deviation

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Acknowledgements

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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Authors and Affiliations

  1. Department of Biochemistry, Institute of Chemical Technology in Prague, Technická 5, 166 28, Prague 6, Czech Republic

    Vojtěch Spiwok, Petra Lipovová & Blanka Králová

  2. Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovskeho náměstí 2, 162 06, Praha 6, Czech Republic

    Tereza Skálová, Eva Vondráčková,  Jan Dohnálek & Jindřich Hašek

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  1. Vojtěch Spiwok
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  2. Petra Lipovová
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Correspondence to Vojtěch Spiwok.

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Spiwok, V., Lipovová, P., Skálová, T. et al. Modelling of carbohydrate–aromatic interactions: ab initio energetics and force field performance. J Comput Aided Mol Des 19, 887–901 (2005). https://doi.org/10.1007/s10822-005-9033-z

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  • DOI: https://doi.org/10.1007/s10822-005-9033-z

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