As noted, an MC move can be performed at the midpoint of the NCMC protocol. In our original paper describing the BLUES method, the only such move offered was a center of mass rotation of the ligand. In subsequent work, the MC moves available were further expanded to include protein side-chain torsions as well as selected torsions of the ligand. These types of moves are helpful in generating small perturbations of the ligand's binding mode, but ideally we would like to be able to generate binding mode predictions and sample between those directly. Generally, proposing reasonable candidate binding modes is a relatively easy task, since docking methods tend to do a good job at generating plausible binding modes, but are poor at ranking these binding modes. In many cases, such poses can be equilibrated via MD simulations to find a variety of different stable or metastable binding mode candidates. While some methods can improve sampling of a ligand's internal degrees of freedom, we are not aware of any current MC method which can efficiently hop between potentially disparate predefined ligand binding modes in a way that preserves detailed balance.