Absolute binding free energy (ABFE) calculations have some benefits over relative ones (RBFE), but are thought to require more sampling because of the generally larger transformations involved compared to RBFE. In ABFE calculations, ligands of interest can be very chemically diverse since they need not share a common scaffold. In addition, different ligands need not share a common binding mode. The method can even be used for selectivity predictions, predicting binding of a ligand to multiple proteins. However, ABFE calculations are thought to require more sampling and simulations may take a long time to converge which can make them computationally expensive. ABFE calculations in some systems likely require additional sampling of slow protein motions relative to RBFE calculations, such as changes in protein conformation which occur on ligand binding (e.g. HIV protease flap opening/closing, kinase activation loop, 10 etc.).