However, the overall acceptance probability is not the only consideration -we are also interested in how each technique improves the acceptance of substantial moves that significantly alter the ligand binding mode. After all, when proposing random ligand rotational moves, a rotation of zero, or of very nearly zero, is a valid move proposal, so potentially many of the moves being accepted are in fact very small ligand rearrangements. To examine this, we determined the fraction of rotational moves accepted as a function of amount of rotation (Figure ), both for toluene and for 3-iodotoluene.