This work was conducted in the Mobley Lab at UC Irvine (SW and DLM). Regular project check-ins were done with PTM and CB. Input files during the early-stage development of the project were prepared by YG. Design of the ABFE thermodynamic cycle and initial test runs were performed by PTM, with suggestions from CB and DLM. Simulations for the ABFE systems and the RBFE calculations were performed by SW. SW and PTM wrote the manuscript. All authors reviewed the paper and many contributed to editing.