Adequate KB integral convergence was observed with R = 20 Å in most systems, as reported in previous publications . The solution volume closer to the solute than this distance was considered the "protein domain", while the volume outside this domain was used to deduce the structure and thermodynamic properties of the solution without the protein. Effective bulk concentrations of the solutions were obtained from the simulations by computing the density of each solvent in the region between 20 and 30 Å from the protein surface, thus from an open subsystem of the simulation, minimizing finite-size effects .