Simulation parameters of composition, temperature, and pressure were chosen to match experimental conditions. Based on the initial configuration, the steepest descent method was used to minimize the energy of the system, followed by an initial equilibration of 15 ns, in which temperature and pressure were kept constant by using the v-rescale thermostat and Parrinello-Rahman barostat algorithm, respectively. Following equilibration, an additional 5.0 ns were used for sampling. Periodic boundary conditions were applied in the x, y, and z directions, and the leapfrog algorithm was used to integrate the equation of motion with a time step of 2 fs. Hydrogen bonds constrained using the LINCS algorithm. Radial distribution functions (RDFs) and hydrogen bond analyses were obtained using Gromacs built-in analysis tools. Finally, Travis was used to obtain the water-water and solvent-water plane projection distribution (PPD). The ddG technique described above was also applied to the PDFs generated by MD simulations, allowing comparisons between computationally-and experimentally-derived ddGs.