MOLECULAR RECOGNITION .14. MONTE-CARLO SIMULATION OF THE HYDRATION OFTHE 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 angstrom resolution. The regions of the combining sites are identical shallow polyamphiphil ic cavities with a surface area of approximately 240 angstrom2 and an average depth of only about 2.2 angstrom. To reduce the CPU time requi rements for Monte Carlo simulations of the hydration of the combining site of the native lectin, a fragment of the protein structure was exa mined that contained only 62 of the 243 amino acid residues and was pr esent in both of the two subunits of the protein. This portion of the lectin, which encompassed the combining site and its immediate surroun dings, was examined, employing 250 water molecules to near symmetrical ly cover an area of about 370 angstrom2 over and about the combining s ite with a density of 1 at 300 K. As was previously found in similar s tudies of the hydration of the Lewis b tetrasaccharide, the nonpolar r egions 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 va rying dimensions. It is expected, therefore, that the association of c omplementary hydrophilic surfaces in aqueous solution must involve, in addition to the establishment of the usual intermolecular forces of a ttraction, 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 (hi gher density) and through an increase in entropy (greater disorder). T his property of hydrated polyamphiphilic surfaces may contribute impor tantly to the driving force of all associations in aqueous solution si nce virtually all organic molecules are polyamphiphilic in character.