One notable feature of Figure is that in the region of shorter switching times (>1000 switching steps) there is a decrease of acceptance compared to instantaneous MC. This has been obverved previously with NCMC, and in our case might arise from the asymmetric work distributions associated with removing and restoring the ligand's interactions Figure : Acceptance probability for toluene as a function of the amount of NCMC relaxation. The acceptance probability-also referred to as the acceptance rate-is shown on a log scale as a function of the total number of NCMC switching steps per cycle, for toluene in the L99A site of T4 lysozyme. The acceptance probability increases dramatically up to 10000 NCMC switching steps per cycle, then increases more slowly, so much of our work in this study focuses on comparing efficiency with other approaches at 10000 steps per cycle. The red dashed line marks the acceptance probability of instantaneous conventional MC rotations without an accompanying NCMC protocol, i.e. standard MC for ligand rotation. Error bars are the standard error in the acceptance rate (Sec. 2.5.3).