Using the calculation described above, we obtain 15.73 ± 0.08 transitions per million f-ev with MD/NCMC, which is about a three order of magnitude improvement over standard MD. We obtain an acceptance rate of 12.7 ± 0.7% for the NCMC moves, which is similar to 11% obtained by Gill et al. in previous MD/NCMC work on rigid fragments. Unlike standard Monte Carlo, the ideal efficiency rate is not close to 23% in NCMC but instead is a strong function of the size/importance of the moves. Particularly even low acceptance of important moves can provide dramatic sampling enhancements, as discussed in the prior NCMC paper. 4.2. Choice of alchemical region important for increasing acceptance rates. During the NCMC move proposal, we preselect only the part of the ligand that moves due to rotation of the rotatable bond. We alchemically turn on and off only this region. However in previous work by Gill et al., the whole ligand was specified as the alchemical region. Hence, we investigated the effect of different alchemical regions on move acceptance rates, which in turn affects the convergence time.