where N 0 is the number of GCMC molecules in the sphere at the start of a move and N T is the number of molecules at the end. It should be noted that if the molecule being switched lies outside the sphere by the end of the move, the move must be automatically rejected since the reverse process cannot be proposed, breaking the condition for detailed balance. Depending on the characteristics of the binding site, this can sometimes lead to a high number of moves being rejected.