All simulations were run using the GROMACS 57 simulation package version 2020 and analyzed with in-house developed Python 3 programs using the MDAnalysis package . We also used the IPython 60 , numpy 61 , SciPy 62 , scikit-learn 63 , Voro++ 64 , and matplotlib 65 packages for scientific computing in Python. Visualization and rendering of the simulations were performed with the molecular graphics viewer VMD . Analysis methods part of the GROMACS tool suite were also used . Octanol-water partition free energies were calculated from the individual CG solvation free energies into each solvent, as described elsewhere . See the Methods section of the Supporting Information for details on specific analysis methods.