In order to minimize computational cost and considering that the reaction does not proceed via a covalent intermediate, the catalytic cysteine side chain and the entirety of the substrate was used as our QM region. This truncated QM region enabled more extensive sampling of the environment. The QM region was described using the ωB97X-D3 functional and the 6-31+G(d) basis set, with the surrounding protein being described using the ff94SB force field, as described in the supporting information.