The applications of multiscale quantum-classical (QM-MM) approaches have shown an extraordinary expansion and diversification in the last couple of decades. A great proportion of these efforts have been devoted to interpreting and reproducing spectroscopic experiments in a variety of complex environments such as solutions, interfaces, and biological systems. Today, QM-MM-based computational spectroscopy methods constitute accomplished tools with refined predictive power. The present review summarizes the advances that have been made in QM-MM approaches to UV-visible, Raman, IR, NMR, electron paramagnetic resonance, and Mössbauer spectroscopies, providing in every case an introductory discussion of the corresponding methodological background. A representative number of applications are presented to illustrate the historical evolution and the state of the art of this field, highlighting the advantages and limitations of the available methodologies. Finally, we present our view of the perspectives and open challenges in the field.

Peroxiredoxins (Prxs) catalyze the reduction of peroxides, a process of key relevance in a variety of cellular processes. The first step in the catalytic cycle of all Prxs is the oxidation of a cysteine residue to sulfenic acid, which occurs 103-107 times faster than in free cysteine. We present an experimental kinetics and hybrid QM/MM investigation to explore the reaction of Prxs with H2O2 using alkyl hydroperoxide reductase E from Mycobacterium tuberculosis as a Prx model. We report for the first time the reaction thermodynamical activation parameters of H2O2 reduction by a Prx, which show that the protein lowers significantly the activation enthalpy, with an unfavourable entropic effect, compared to the uncatalyzed reaction. The QM/MM simulations show that the remarkable catalytic effects responsible for the fast H2O2 reduction in Prxs are mainly due to an active-site arrangement, which establishes a complex hydrogen bond network activating both reactive species.