Relative stability of the S₂ isomers of the oxygen evolving complex of photosystem II

The oxidation of water to O₂ is catalyzed by the Oxygen Evolving Complex (OEC), a Mn₄CaO₅ complex in Photosystem II (PSII). The OEC is sequentially oxidized from state S₀ to S₄. The S₂ state, (Mn^III)(Mn^IV)₃, coexists in two redox isomers: S_2,g=2, where Mn4 is Mn^IV and S_2,g=4.1, where Mn1 is Mn^IV. Mn4 has two terminal water ligands, whose proton affinity is affected by the Mn oxidation state. The relative energy of the two S₂ redox isomers and the protonation state of the terminal water ligands are analyzed using classical multi-conformer continuum electrostatics (MCCE). The Monte Carlo simulations are done on QM/MM optimized S₁ and S₂ structures docked back into the complete PSII, keeping the protonation state of the protein at equilibrium with the OEC redox and protonation states. Wild-type PSII, chloride-depleted PSII, PSII in the presence of oxidized Y_Z/protonated D1-H190, and the PSII mutants D2-K317A, D1-D61A, and D1-S169A are studied at pH 6. The wild-type PSII at pH 8 is also described. In qualitative agreement with experiment, in wild-type PSII, the S_2,g=2 redox isomer is the lower energy state; while chloride depletion or pH 8 stabilizes the S_2,g=4.1 state and the mutants D2-K317A, D1-D61A, and D1-S169A favor the S_2,g=2 state. The protonation states of D1-E329, D1-E65, D1-H337, D1-D61, and the terminal waters on Mn4 (W1 and W2) are affected by the OEC oxidation state. The terminal W2 on Mn4 is a mixture of water and hydroxyl in the S_2,g=2 state, indicating the two water protonation states have similar energy, while it remains neutral in the S₁ and S_2,g=4.1 states. In wild-type PSII, advancement to S₂ leads to negligible proton loss and so there is an accumulation of positive charge. In the analyzed mutations and Cl^- depleted PSII, additional deprotonation is found upon formation of S₂ state.