The coordinates of the host, βCD, were taken from a review by Mobley et al. and solvated in TIP3P water with an 8 Å buffer. GCNCMC/MD titrations were performed with a switching time of 50 ps (n pert = 499 and n prop = 50). The GCMC region was defined as a sphere with a 5 Å radius centered in the host cavity midway between two carbon atoms on either side of the host. A total of 22 ligands, from two different studies, with experimental binding affinities were selected for titration and are shown in Figure . Excess chemical potentials for the ligands were calculated as described above and are reported in the SI. Titration B values (n=20) were chosen to loosely surround the experimental dissociation constant. 1700 cycles of GCNCMC/MD were performed at each B value with the first 200 being discarded as equilibration. In these simulations, each cycle consisted of a GCNCMC move attempted for every 1 ps of MD. Each B value was simulated for four repeats.