Alchemical ABFE calculations are computationally intensive. Table summarises the computational costs associated with them using both the "standard" as well as the "minimum" protocols recommended in this study (see Table in Discussion). Using the standard recommended protocol (employed in this study), the simulation time requirement for a single ABFE calculation using the NEQ approach is only about 10% cheaper than the EQ approach. The aggregate simulation time invested for this entire study covering both EQ and NEQ methods and including all simulations required for the various systematic analyses is over 3 milliseconds.