In order to confirm theoretical system models of photosystem II (PSII), quantum mechanics (QM)/molecular mechanics (MM) calculations using a large-scale QM model (QM Model V) have been performed to elucidate hydrogen bonding networks and proton wires for proton release pathways (PRPs) of water oxidation reaction in the oxygen-evolving complex (OEC) of PSII. Full geometry optimizations of PRP by the QM/MM model have been carried out starting from the geometry of heavy atoms determined by the recent high-resolution X-ray diffraction (XRD) experiment on PSII refined to 1.9Å resolution. The optimized MnMn and CaMn distances by large-scale QM/MM are consistent with the EXAFS results, removing out the discrepancy between the refined XRD and EXAFS. Computational results from QM/MM calculations have demonstrated the labile nature of the MnaO(5)Mnd bond of the CaMn4O5 cluster in the OEC of PSII which allows left (L)-opened, quasi-central (CQ)-, and right (R)-opened structures. This confirms the feasibility of the left- and right-hand scenarios for water oxidation in the OEC of PSII that are dependent on the hydrogen bonding networks. The QM/MM computations have elucidated the networks structures: hydrogen bonding O. . .O(N) and O. . .H distances and O(N)H. . .O angles in PRP, together with the ClO(N) and Cl. . .H distances and O(N)H. . .Cl angles for chloride anions. The obtained hydrogen bonding networks are fully consistent with the results from XRD and available experiments such as EXAFS, showing the reliability of our theoretical system model that is crucial for investigations of functions of PSII such as water oxidation. The QM/MM computations have elucidated possible roles of chloride anions in OEC of PSII for proton transfers. The QM/MM computational results have provided useful information for the understanding and explanation of several experimental results obtained with mutants of the OEC of PSII. The possible implications of the present results are discussed in relation to our theoretical system models of PSII, strong or weak perturbations of the system structures by mutations, damage-free X-ray free-electron laser structure of PSII, and bioinspired working hypotheses for the development of artificial water oxidation systems which use 3d transition metal complexes.