Therefore, as can be seen from Table and Figure , when only a few simultaneous substitutions are involved in generating the computationally predicted structure (as in our prior work ), or where a crystal structure of a variant with multiple amino acid substitutions is available, the EVB approach can reproduce experimental data with high fidelity in a wide range of systems. In addition, considering the potentially large structural perturbations involved, agreement within 2 kcal•mol -1 of experiment is still respectable, in line with or better than the agreement with experiment obtained in other computational studies of Kemp elimination, and thus gives EVB great potential as a predictive tool for more complex reactions where the introduction of mutations have a larger energetic impact on the system, and thus better correlation with experiment would be expected as observed for example in refs. . Therefore, we believe the EVB simulations can already act as a first step filter over the Rosetta scores predicted by FuncLib, as the latter in this case provided no correlation with experimental activities, despite being able to effectively predict variants with improved activity.