In this study, we propose a way to implicitly account for such systematic errors (denoted as ∆G prot conf ) in predicted ABFEs. We assume for convenience that such errors for all ligands binding to the same pocket of the target protein are approximately same. Therefore, we aim to determine a constant that may be used as an empirical estimate of the average error for all such ligands. Such an empirical estimate of ∆G prot conf can be used to adjust the predicted ∆G values. In this case, we use the mean signed error (MSE) value for all ligand-protein complexes belonging to the same system as the empiricial estimate of ∆G prot conf . A similar approach has also been independently proposed by Chen et al. where they used the difference between the average raw predicted ∆Gs and the average experimenal ∆Gs. contains the values of such errors for all systems studied using both approaches.