Molecular dynamics simulations of the interaction of glucose with imidazole in aqueous solution

Molecular dynamics simulations were carried out on a concentrated system of β-d-glucopyranose and imidazole molecules in a periodic box of water at 298 K. The purpose of the simulations was to determine whether or not there was any tendency for these two solutes to associate in an aqueous environment, as has previously been observed for other planar functional groups from amino acid side chains, such as the indole group of tryptophan or the phenolic group of tyrosine. A weak stacking interaction between β-d-glucopyranose, as a model for cellulose, and imidazole was indeed observed, with an energy of ∼0.25 kcal/mol per pair, less than kT. Somewhat surprisingly, considerable imidazole self-association into small aggregates (dimers and trimers) was also observed, with binding energies of ∼0.4 kcal/mol per pair, although still less than kT. Considerable non-stacked interactions between glucose and imidazole through hydrogen bonding were also found. These hydrogen bonds primarily involved the N3 atom of imidazole, because the N–H group of N1 was insufficiently polar to compete for water hydrogen bond partners.

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► Glucose stacks against the faces of imidazole with binding energy of ∼0.5 kcal/mol.
► Imidazole molecules bind to one another with a binding energy of ∼0.8 kcal/mol.
► Both types of binding are due to unfavorable interactions with solvent water.
► However, imidazole is too small to hydrate as an extended hydrophobic surface.