High-order MBE calculations quickly become intractable due to combinatorial growth in the number of subsystems, which creates follow-on difficulties for maintaining precision. Therefore, a screening mechanism to reduce the number of subsystems is vital to large-scale deployment of fragmentation, but simple distance-based screening can miss energetically important subsystems. We have shown that energy-based screening is superior in both accuracy and efficiency, 145 and this type of screening is native to the Fragme∩t software used here. We next test the effects of screening on MBE(4) interaction energies for F -(H 2 O) 15 , computed at either the HF/aQZ level or the PBE/aQZ level. In either case, three-body fragments are screened using the semi-empirical GFN2-xTB model 146 with an adjustable threshold τ 3 . Four-body subsystems are created from energetically important three-body subsystems, allowing for M = 1 missing parents. This means that tetramer IJKL is included if at least three of its four three-body sub-clusters is above threshold (e.g., |∆E IJK | > τ 3 ). This procedure has previously been shown to afford energetically converged four-body expansions. HF/aQZ results in Fig. exhibit minimal error in ∆E int when all three-body terms are retained (τ 3 = 0). Errors increase as τ 3 increases and the screening becomes more aggressive but remain small for τ 3 ∼ 0.1 kcal/mol, a value that also affords good results for neutral water clusters. In Fig. , the same HF/aQZ errors are plot- ted as a function of the number of subsystems included in the calculation. As expected, errors decrease as the calculation becomes more complete, up to a certain point (around 500 subsystems) when all energetically important terms have been incorporated and there is no further benefit to tightening τ 3 , and perhaps some noise introduced as the number of subsystems increases.