Ab Initio Simulations of Two-Dimensional Electronic Spectra: The SOS//QM/MM Approach 2DES spectra based on accurate characterization of the electronic structure of multichromophoric systems is crucial. Ab initio quatum chemistry

Two-dimensional electronic spectroscopy (2DES) is a cutting-edge technique for investigating with high temporal resolution energy transfer, structure, and dynamics in a wide range of systems in physical chemistry, energy sciences, biophysics, and biocatalysis. However, the interpretation of 2DES is challenging and requires computational modeling. This perspective provides a roadmap for the development of computational tools that could be routinely applied to simulate 2DES spectra of multichromophoric systems active in the UV region (2DUV) using state-of-the-art ab initio electronic structure methods within a quatum mechanics/molecular mechanics (QM/MM) scheme and the sum-over-states (SOS) approach (here called SOS//QM/MM). Multiconfigurational and multireference perturbative methods, such as the complete active space self-consistent field and second-order multireference perturbation theory (CASPT2) techniques, can be applied to reliably calculate the electronic prop-erties of multichromophoric systems. Hybrid QM/MM method and molecular dynamics techniques can be used to assess environmental and conformational effects, respectively, that shape the 2D electronic spectra. DNA and proteins are important biological targets containing UV chromophores. We report ab initio simulation of 2DUV spectra of a cyclic tetrapeptide containing two interacting aromatic side chains, a model system for the study of protein structure and dynamics by means of 2DUV spectroscopy. V C 2013 Wiley Periodicals, Inc. DOI: 10.1002/qua.24511 are found in the UV, such as proteins and DNA (or RNA). Accurate simulations of 2DUV signals are crucial for the analysis and the interpretation of complex 2D spectra. We present a computational strategy for first-principle simulations of 2DUV signals using QM state-of-the-art (CASPT2//CASSCF) wavefunctions within a QM/MM scheme and combined with the SOS approach. Its application to a model proteic system, a small oligopeptide containing two UV-active aromatic side chains, is shown. The proposed ab initio simulations are able to resolve off-diagonal peaks in the 2D spectra that contain structural information of the oligopeptide and chromophore–chromophore electronic coupling between aromatic residues, beyond standard Frenkel EMs. Future integration of thermal fluctuation effects on 2DUV spectra is necessary for proper characterization of signal broad-enings and linewidths, allowing for suitable comparison with experimental data.