We adapted the thermodynamic cycle to incorporate this enhanced sampling method. In leg B of the thermodynamic cycle (Figure ), instead of fully turning on the vdW interactions of the green ligand, vdW interactions were only partially turned on to the modified LJ-ϵ (scaled atom type as described above). At the same time, the vdW interactions of the magenta ligand are partially turned off by transitioning from the original atom type to the scaled atom type. Both ligands have part of their vdW interactions turned on, and therefore, in the new leg D of the ϵ-HREX protocol, the vdW interactions of the magenta ligand are now fully turned off while the vdW interactions of the green ligand are fully being turned on. We compared the performances of this ϵ-HREX protocol with a protocol that did not use enhanced sampling in Section 5.1.