The Transient Reactor Test (TREAT) Facility at Idaho National Laboratory (INL) started testing new fuels and reactor technologies once again in 2018 and new experiments and tests are currently being designed like for example the water loop “TREAT Water Environment Recirculating Loop” (TWERL). During the design of such experiments, the designer must assess how close the experiment reproduces the physics (and other important phenomena) happening during a transient of interest compared to the full-size reactor the experiment attempts representing. Traditionally, to assess this “representativity” of the experiment, scaling theory involving expert judgment is needed. This paper presents a step towards a systematic modeling and simulation (M&S) informed methodology for experiment design. The new methodology compares a model of the full system and a model of the mock-up facility that are subject to the same perturbations. In this way, the “overlap” of the perturbed experiment and full-size facility model outputs can be analyzed and the “representativity” of the experiment determined. The paper presents a RELAP5-3D analysis, where TWERL LOCA calculations are compared to prototypic PWR LOCA calculations with respect to representativity. To inform the design of the TWERL experiments, i.e. to find the most “representative” configuration for the TWERL loop, different design parameters for TWERL have been optimized in the study.