The primary goal of this work is to demonstrate that fragment-based semi-empirical calculations can be used as an efficient means to test convergence of automated procedures for QM model construction in enzyme calculations. To do so, we first validate the use of HF-3c against conventional DFT, in Section 3 .1. We then consider energy screening of the two-body HF-3c calculations in Section 3 .2, which further improves the efficiency. The resulting method is used in Section 3 .3 to evaluate the convergence of ∆E int for various bindingsite models. Comparisons to DFT results are presented in Section 3 .4.