To improve sampling of a particular region of interest, the user can target GCNCMC moves by defining a spherical "GCMC region" to cover this region. For example, this could be a known binding site or the whole protein (Fig. ). However, the use of a sphere for GCNCMC moves requires special care, in that molecules can potentially diffuse into or out of the sphere throughout the switch, meaning that the acceptance ratios defined previously must be adjusted: