  The solvation of charged, nanometer-sized spherical solutes in water, and the
effective, solvent-induced force between two such solutes are investigated by
constant temperature and pressure Molecular Dynamics simulations of model
solutes carrying various charge patterns. The results for neutral solutes agree
well with earlier findings, and with predictions of simple macroscopic
considerations: substantial hydrophobic attraction may be traced back to strong
depletion (``drying'') of the solvent between the solutes. This hydrophobic
attraction is strongly reduced when the solutes are uniformly charged, and the
total force becomes repulsive at sufficiently high charge; there is a
significant asymmetry between anionic and cationic solute pairs, the latter
experiencing a lesser hydrophobic attraction. The situation becomes more
complex when the solutes carry discrete (rather than uniform) charge patterns.
Due to antagonistic effects of the resulting hydrophilic and hydrophobic
``patches'' on the solvent molecules, water is once more significantly depleted
around the solutes, and the effective interaction reverts to being mainly
attractive, despite the direct electrostatic repulsion between solutes.
Examination of a highly coarse-grained configurational probability density
shows that the relative orientation of the two solutes is very different in
explicit solvent, compared to the prediction of the crude implicit solvent
representation. The present study strongly suggests that a realistic modeling
of the charge distribution on the surface of globular proteins, as well as the
molecular treatment of water are essential prerequisites for any reliable study
of protein aggregation.
