SOLVENT-INDUCED FORCES BETWEEN 2 HYDROPHILIC GROUPS

Molecular dynamics simulations were used to calculate the force betwee n two simple hydrophilic solutes in dilute aqueous solution. The ''sol utes'' were two water molecules in the same relative orientation as th e next-nearest neighbors in hexagonal ice I. Both the direct and solve nt-induced contributions to the force were calculated as a function of separation distance. The total force between the solutes was found to be most attractive at 5.0 Angstrom (-1.6 kcal/mol/Angstrom). The pote ntial of mean force had a minimum at 4.3 Angstrom, which is 0.2 Angstr om closer than the next-nearest-neighbor distance in ice. A parallel s et of simulations were conducted with the partial charges on the ''sol utes'' removed to examine hydrophobic analogs. In this case, the total force was most attractive at 3.5 Angstrom (-0.9 kcal/mol/Angstrom), a nd the minimum of the potential was at the contact distance of 3.2 Ang strom. In agreement with earlier predictions, the maximum solvent-indu ced contribution to the potential was ca. 4 times more negative for th e hydrophilic ''solutes'' than for the hydrophobic ones, These differe nces are shown to be due predominantly to a solvent water molecule whi ch simultaneously hydrogen bonds to both hydrophilic ''solutes''. The results support earlier assertions that solvent-induced interactions b etween polar amino acid residues are more important in protein folding and stability than generally considered.