Four systems were selected for our investigation, and are summarised in Table : P38α and PTP1B were taken from the work of Wang et al . The ligand poses were further adjusted by Gapsys et al , and are generally considered to be of high quality. Additionally, we selected TNKS2 and SYK from the work of Schindler et al . The original ligand poses from this study were generated primarily by core-constrained docking using Glide, however, in the case of multiple poses, charge states, or tautomers, all plausible combinations were calculated by FEP+, and the pose with the lowest predicted binding free energy was reported as the input structure. All input data used in this work is available in the SI.