To reduce the computational effort for the evaluations of this sensitivity for each amino acid, we assessed several possible simplifications compared to the global PCVA in the previous section. The different levels of simplification are referred to as PCVA-A to PCVA-E, and the sensitivities obtained in these different approximations are shown in Fig. . First, instead of the full QM/MM reaction energy (PCVA-A) we use only the QM contribution (PCVA-B), i.e., the approximation of Eq. ( ) is employed. This is justified as the effect on the QM energy is the main focus of the analysis and possible undesired MM-only effects will be excluded. Furthermore, no significant differences in the calculated sensitivities are observed comparing the full and QM energy approach. Second, instead of the reaction energy we could use the sensitivity of the product (PCVA-C) or reactant (PCVA-D) energy instead.