Molecular recognition XIV. Monte Carlo simulation of the hydration of the combining site of a Lectin

Monte Carlo simulations of the hydration of the combining sites of the divalent lectin IV of Griffonia simplicifolia were carried out using the X-ray structure of the native lectin at 2.15 Å resolution. The regions of the combining sites are identical shallow polyamphiphilic cavities with a surface area of approximately 240 Å2 and an average depth of only about 2.2 Å. To reduce the CPU time requirements for Monte Carlo simulations of the hydration of the combining site of the native lectin, a fragment of the protein structure was examined that contained only 62 of the 243 amino acid residues and was present in both of the two subunits of the protein. This portion of the lectin, which encompassed the combining site and its immediate surroundings, was examined, employing 250 water molecules to near symmetrically cover an area of about 370 Å2 over and about the combining site with a density of 1 at 300 K. As was previously found in similar studies of the hydration of the Lewis b tetrasaccharide, the nonpolar regions are much less densely hydrated than the adjacent polar regions. This situation is considered to arise because of the hydrogen-bonding requirement for water molecules to bridge over nonpolar regions of varying dimensions. It is expected, therefore, that the association of complementary hydrophilic surfaces in aqueous solution must involve, in addition to the establishment of the usual intermolecular forces of attraction, a collapse of water structure over "flickering cavities" for return to bulk. This collapse can be expected to contribute to the driving force for association both through a decrease in enthalpy (higher density) and through an increase in entropy (greater disorder). This property of hydrated polyamphiphilic surfaces may contribute importantly to the driving force of all associations in aqueous solution since virtually all organic molecules are polyamphiphilic in character.