In order to confirm that the proton transfers are not an artifact of the size of the QM region being used, we carried out a set of QM/MM calculations on input structures 1-23 with the much larger 13 residue, QM Region II (Figure ). QM Region II included three additional residues (i.e., Pro 395, Phe397, Ala399) modeled in the QM study of Gupta et al. Two more proline residues (Pro396, Pro398) had to be included because QSite allows parameterized cuts of proline only along the C-Cα bond. The resulting optimized structures have many similarities with the optimized structures found using the 8 residue QM Region I. Table in the Supplementary Material compares the results of these optimizations regarding the transfer of hydrogen(s). There