The excess chemical potential of a molecule is defined as the free energy of adding a molecule to a given solution and is crucial in determining whether a given fragment would prefer to be in solution, or a binding site. In this work, we approximate the excess chemical potential of a given fragment to be equal to the "infinite dilution" hydration free energy of that fragment, or in other words, the free energy of adding a fragment molecule to a box of water. However, it should be emphasized that the value of µ ′ sol can also be influenced by interactions with other molecules of the same type and in theory also has a concentration dependence. Nevertheless, for sufficiently dilute concentrations such as those used in these studies, it is assumed that the impact of these interactions is negligible and that µ ′ sol is independent of concentration. As a result, for a given molecule, only one value of µ ′ sol requires calculation, and this value can be applied to any dilute concentration of that molecule. A full discussion on this point, with data, can be found in the Supplementary Information.