Panels in Fig. illustrate structural features of the ON-state models in the ground electronic state S0. Panel (b) shows a superposition of the key fragments of the active site from the QM/MM optimized structure (colored balls and sticks) and those from the crystal structure PDB ID 3ST4 (yellow stick). The central panel (b) illustrates the QM/MM optimized active site with the neutral form of Chro, whereas the panel (e) shows this site with the anionic Chro. The QM/MM energy of the model system with the neutral Chro is only1 kcal/mol lower that the energy of the system with the anionic Chro. According to the experimental absorption spectra of the protein in the ON state , both protein conformations (with the neutral and anionic Chro) are observed in the experiments. We comment that the geometry parameters optimized for the full-protein model at the QM/MM level are well consistent with the crystal structure PDB ID 3ST4 assigned to the ONstate . In particular, this refers to the almost coplanar arrangement of the rings of the phenolic part of Chro (P-ring) and of the Tyr203 side chain, to the distance between Chro and His145, and even to the distances from the reactive water molecule Wat to Chro and Tyr203. Configurations of the Chro-Wat-Tyr203 subsystem are of a particular importance for the modeling. Panels (b, c) show the important features, common for the GFP-like proteins, namely, the proton wires connecting the groups around Chro. Here, we distinguish the following proton translocation pathways: wire-1, connecting the Glu222 and His145 side chains (from Oε1(Glu) to Nδ(His) via Ser205 and water molecules Wat' and Wat''); wire-2, connecting Glu222 and Chro (from Oε1(Glu) to OH(Chro) via Ser205 and water molecules Wat' and Wat''); wire-3, connecting Chro and His145 (from OH(Chro) to Nδ(His) via Wat''). Wire-1 connects two possible protonation forms in the active site of the protein, neutral His145 and Glu222, and positively charged doubly protonated His145 and negatively charged deprotonated Glu222. Both forms can contribute to protein conformations; however, the analysis carried out in Ref. favors the conformation with the neutral His145 and Glu222, as depicted in Fig. . Another short wire-3 accounts for the formation of the anionic Chro; this occurs if the proton initially bound to the OH atom in the neutral form of Chro transfers to the Nδ atom in His145. If this process takes place, and Wat'' re-orients, wire-2 operates as a conventional proton translocation pathway in the GFP-like proteins connecting Chro and Glu (panel (c)).