First, Packmol was used to generate initial structures . This was followed by 3,000 steepest descent minimization steps to remove any bad contacts that might have resulted from the packing. The next two steps involved dynamics with the equations of motion integrated using the Verlet leap-frog algorithm . The system was first equilibrated in an NPT ensemble at 298.15 K and 1 bar for 1 ns using the Berendsen thermostat and barostat . This was followed by 4 ns of equilibration in an NPT ensemble at the same conditions using the stochastic velocity rescaling thermostat and the Parrinello-Rahman barostat . The final structure from this series of simulations was then used as the initial structure for our free energy calculations, as will be described momentarily. For systems involving SAMPL7 molecules SM30, SM33, SM34, SM36, SM37, and SM39, the final NPT equilibration was continued for an additional 100 ns which was used for subsequent structural analysis.