For this, we carried out MFES, FEP, and NEQ switching simulations using a subset of 18 molecules taken from the HiPen dataset (for more details on the dataset, see the Methods section). We performed MFES, uni-and bidirectional FEP, and 5 ps, 10 ps, 20 ps, and 50 ps uni-and bidirectional NEQ switching simulations. The results are summarized in Figure . In the Supplementary Materials section, you can find comprehensive details about each system, the results obtained with each of the different methods to estimate the free energy, and the free energy results with varying NEQ switching lengths. The detailed results