Calculation of the potential of mean force for the binding of glucose to benzene in aqueous solution

Molecular dynamics simulations employing umbrella sampling techniques have been used to calculate the potential of mean force (pmf) for the binding of a beta-D-glucopyranose molecule to a benzene molecule in aqueous solution, as a model for the binding of sugar substrates to phenylalanine residues i n proteins. The interaction of these two molecules was found to be strongly affected by hydration, as expected, with their nonpolar faces pairing by h ydrophobic association to minimize the exposure of apolar groups to water. The pmf for the approach of these molecules is oscillatory in character, wi th two primary low-energy minima separated by a high free energy barrier, a nd with the net binding energy being approximately 1.1 kcal/mol and the int ervening barrier being almost 2 kcal/mol. A third, weaker minimum was obser ved between 11 and 12 Angstrom. The oscillatory nature of the pmf results f rom the successive removal of water layers between the two molecules as the y approach one another.