# Artificial Photosynthesis: Is Computation Ready for the Challenge Ahead?
## 2 Light Harvesting
### QM/MM-Based Approaches  
As early as 2011, [PERSON] et al. [47] considered a QM/MM method using various (TD)-DFT approaches to describe the absorption properties of LHCII and chlorophyll pigments (Chl) of green plants while explicitly consider environmental effects (Figure 2c,d). The protein environment is here considered as \"test environments\" in which only the amino acids closest to the QM region are considered. The response of the environment to the changes in charge distribution of the pigments during excitation have been accounted for by use of polarizable models, in which the environment is considered classically, as described in the generalization of the frozen-density-embedding (FDE) for excited states [48; 49] in which the environment is considered at the QM level, without system-specific parametrization. With this methodology, the authors calculated the changes of site energies of all chlorophyll pigments in LHC II and the absorption spectrum of the complete chlorophyll network (the total system has more than 1000 atoms). They concluded that while carrying partial optimization with some structural constrains, the protein environment should be explicitly taken into account. Alternatively, sampling can be done over a number of different conformations of the pigments in the protein. From these calculations, the authors compute the absorption spectra of the complete Chl network and identified which pigment mediates the electronic coupling mixing (acting as bridges) between other pigments. Thus, this TD-DFT FDE based approach allows to investigate environmental and exciton-coupling effects of a network of pigments in protein complexes in a full QM treatment beyond the standard Kohn-Sham approach. Recently, [PERSON] et al. [50] considered a newly developed polarization-consistent framework [51] which combines PCM with TD-DFT by using a screened range-separated hybrid functional (SRSH) to assess the absorption properties of the bacterial reaction center (BRC, Figure 2e). This method is computationally efficient and accurate for obtaining both ground and excited state properties of molecular systems in which polarization effects should be considered. The authors analyzed the spectral splitting of pairs of pigments and found that the spectral shift is due to both structural differences and the dielectric environment surrounding the pigments. They conclude that the electronic states of the core pigments of BRC are localized over individual units, and the coupling between pigments is negligible. In addition, they addressed the spectral asymmetry of BRC associated with pseudo-symmetric pairs. SRSH-PCM calculations have been performed combining different dielectric constants assigned to the specific pigment pairs, resulting in a very accurate description of the shifts in excitation energies, which are not found when neglecting the environment. Transition dipole moments are commonly obtained from TD-DFT methods by solving the linear response Casida equation [52], for which the ground state Kohn\(-\)Sham (KS) wave function has to be computed. Despite its wide use, this procedure has two main drawbacks: (i) The solution of the Casida equation become unfeasible for large molecules/complex systems for which a large set of KS orbitals are required, and (ii) the lack of convergence for high lying virtual KS orbitals lead to the failure in describing high energy excitations. Among the variety of developed approaches, the real-time propagation TD-DFT (P-TDDFT) provides an interesting alternative to TD-DFT [53]. It has been verified that P-TDDFT is an excellent platform for studies, among others, of molecular and electron dynamics [54], (non)-linear optics [55] and transport properties [56]. In addition, P-TDDFT allows for the computation of all excitation frequencies at the cost of converging only the occupied ground state KS states [57; 58], strongly reducing the computational cost and allowing the study of systems up to several thousand atoms [59; 60].