Inclusion of four-body terms affords notable improvement in the case of 1ZP5, reducing the error from almost 30 kcal/mol to less than 4 kcal/mol, albeit at significant computational expense. Nevertheless, this demonstrates what seems to be convergent MBE(n) results for the two Zn 2+ -containing enzymes although MBE(4) calculations for 1MMQ are more expensive than the conventional supersystem calculation. Elsewhere, we have addressed this problem using energy-based screening, but that has not been attempted for these systems. MBE(3) remains significantly cheaper than a full-system calculation for these systems, and MBE( ) is at least one order of magnitude less expensive still. This points to the need for future work in which a limited set of energetically important four-body terms might be included in order to recover comparable accuracy at greatly reduced cost, and we are presently implementing this capability within the Fragme∩t code.