The last ten years have seen substantial progress in the use of computational chemistry methods within both academia and the pharmaceutical industry for quantitative structure-based drug discovery, thanks to burgeoning computational power, the increasing number of crystal structures, the accuracy of force fields, the improvement of the sampling methods and control of errors, alongside the automation and general usability of the approaches. Many pharmaceutical companies have adopted free energy predictions as a routine tool to support their drug discovery efforts . This progress has been prompted by Schrödinger's drug discovery platform, especially the FEP+ implementation . There are other packages and workflows used in academia and/or industry, which integrate and automate the process of free energy calculation, including the steps of planning, set up, simulation, and analyses .