The wall clock time requirements for ABFE calculations are also in favour of EQ in comparison to NEQ. In the EQ approach, the wall clock time required for the entire protocol is the same as that of a single simulation as all replicas can be run concurrently on a large supercomputer. On the other hand, in the NEQ approach, the fast transitions need to be run sequentially after the end-state simulations have completed which adds to the wall clock time required (ignoring the set up and waiting time) -another limiting factor in large-scale applications. For instance, a transition length of 400 ps would require 4% extra time that increases to 10% using 1 ns. Once again, the above is also true in the case of RBFE predictions using the NEQ approach which makes it the less preferable approach .