Obtaining the same level of accuracy using a second-order multipole expansion, which systems with respect to the short-range cutoff distance and the order of the multipole expansion used for the long-range coupling (which are indicated with different colors). The points show the mean relative wall times based on single-point calculations on ten snapshots using the full short-range coupling as reference. The cutoff in case of Wat(aq), Ace(aq), and BuOH(ace) is based on distance between fragment centroids and in case of GB1 it is based on interatomic distance.