Combined Multireference–Multiscale\nApproach\nto the Description of Photosynthetic Reaction Centers

A first-principles description of the primary photochemical\nprocesses\nthat drive photosynthesis and sustain life on our planet remains one\nof the grand challenges of modern science. Recent research established\nthat explicit incorporation of protein electrostatics in excited-state\ncalculations of photosynthetic pigments, achieved for example with\nquantum–mechanics/molecular–mechanics (QM/MM) approaches,\nis essential for a meaningful description of the properties and function\nof pigment–protein complexes. Although time-dependent density\nfunctional theory has been used productively so far in QM/MM approaches\nfor the study of such systems, this methodology has limitations. Here\nwe pursue for the first time a QM/MM description of the reaction center\nin the principal enzyme of oxygenic photosynthesis, Photosystem II,\nusing multireference wave function theory for the high-level QM region.\nWe identify best practices and establish guidelines regarding the\nrational choice of active space and appropriate state-averaging for\nthe efficient and reliable use of complete active space self-consistent\nfield (CASSCF) and the N-electron valence state perturbation theory\n(NEVPT2) in the prediction of low-lying excited states of chlorophyll\nand pheophytin pigments. Given that the Gouterman orbitals are inadequate\nas a minimal active space, we define specific minimal and extended\nactive spaces for the NEVPT2 description of electronic states that\nfall within the Q and B bands. Subsequently, we apply our multireference–QM/MM\nprotocol to the description of all pigments in the reaction center\nof Photosystem II. The calculations reproduce the electrochromic shifts\ninduced by the protein matrix and the ordering of site energies consistent\nwith the identity of the primary donor (Chl<sub>D1</sub>) and the\nexperimentally known asymmetric and directional electron transfer.\nThe optimized protocol sets the stage for future multireference treatments\nof multiple pigments, and hence for multireference studies of charge\nseparation, while it is transferable to the study of any photoactive\nembedded tetrapyrrole system.