Discussion of the theoretical requirement for receptor-ligand restraints, derivation of Equation 4, diagram of the syn and anti conformations of MIF-180, parameters for all restraint sets, RMSFs of residues containing anchor points for Boresch restraints, a discussion of challenges and potential improvements related to the restraint selection procedure, a discussion of the force constant fitting procedure, convergence of free energies with simulation time, bound vanish stage PMF and plot of number of waters in the binding site for B3-P, a plot of the number of waters in the binding site during the bound vaish stage for B2-o, a com-