Another way to alleviate the issue of systematic errors in ABFE predictions that is frequently suggested by proponents of the NEQ approach is using both holo and apo structures for the protein environment in the ABFE calculation . This is specific to the NEQ approach as the way ABFE calculations are set up within the NEQ approach, allows one to initiate the fast non-equilibrium transitions from conformations sampled using the apo structure for the coupling process whereas those sampled using the holo structure can be used for the decoupling process. It has been claimed that this will reduce such systematic errors .