title: Modelling of carbohydrate-aromatic interactions: ab initio energetics and force field performance.
abstract: 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/pi 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/pi 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.
authors.affiliation: Department of Biochemistry, Institute of Chemical Technology in Prague, Technická 5, 166 28, Prague 6, Czech Republic. spiwokv@vscht.cz
authors.forename: Vojtech
authors.initials: V
authors.lastname: Spiwok
authors.forename: Petra
authors.initials: P
authors.lastname: Lipovová
authors.forename: Tereza
authors.initials: T
authors.lastname: Skálová
authors.forename: Eva
authors.initials: E
authors.lastname: Vondrácková
authors.forename: Jan
authors.initials: J
authors.lastname: Dohnálek
authors.forename: Jindrich
authors.initials: J
authors.lastname: Hasek
authors.forename: Blanka
authors.initials: B
authors.lastname: Králová
mesh_terms: D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry*; D003198:Computer Simulation; D006841:Hydrocarbons, Aromatic / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D013816:Thermodynamics
chemical_list: D002241:Carbohydrates; D006841:Hydrocarbons, Aromatic