C D Here, it can be seen that in the MD case, only the A2 to B2 and B2 to A2 cases have more than 30 transitions, because the simulation mostly remained stuck in these two states without flipping out-of-plane (Figure ) and a similar effect happened in the MD/MC case but for A1 to B1. In contrast, in the NCMC case, all transitions occur more than 30 times because out-of-plane transitions are also relatively frequent. Iodotoluene is substantially bulkier compared to toluene, and it is difficult to rotate it in the binding site without at least some amount of relaxation, so the acceptance rate for MC moves is lower (Sec. 3.2.3) and the number of significant rotations is dramatically lower (c), with virtually no rotations larger than 22.5 degrees observed; for panel (c) we use a log scale so it is clear that some significant rotations were observed.