Understanding and predicting spectroscopic signatures of biomolecular systems by tailored quantum-chemical approaches

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Spectroscopic techniques have become indispensable tools in many branches of natural sciences. The interpretation of spectroscopic result on atomistic level relies on computational aid. Hence, computational spectroscopic methods are indispensable complements to the experiments. Yet, today’s methods in theoretical spectroscopy are challenged by the large size of biomolecular systems of and the required accuracy for such applications. For electronic spectroscopies, so-called multi-scale approaches have been proven very successful. The philosophy behind multi-scale approaches is to focus the computational effort on certain aspects of a large system and thereby tailor the computational setup to the scientific question of interest. This could, for instance, be a local excitation of a chromophore embedded in a protein. The remaining parts are treated in a more approximate manner. For vibrational wave-function methods, multi-scale approaches are currently hardly developed. They hold, however, an immense potential to accelerate discoveries by vibrational spectroscopy on large molecular systems. This potential will be exploited in the present research program. In the development of multi-scale vibrational wave function methods, also the electronic multi-scale and fragmentations methods will be essential, since accurate electronic potential energy surfaces are a prerequisites for those calculations. In addition, this program will address some remaining challenges in multi-scale methods for emission spectroscopy.The methods to be developed will become valuable tools in theoretical spectroscopy for biomolecular systems the future. Within this research program, we will shed light on the following challenging questions in vibrational and fluorescence spectroscopies. (i) How can we accurately map conformations and local structural changes of hydrogen-bonded systems and proteins to one- and two-dimensional infrared spectra?(ii) What are the atomistic mechanisms behind the discrimination of different amyloid fibrils by fluorescent oligo-thiophene biomarkers?Point (i) is of fundamental interest: A detailed knowledge of protein conformation is indispensable for understanding their function and hydrogen bonds often play crucial roles. The target systems of point (ii), fluorescent biomarkers for amyloid fibrils, are promising candidates for spectral discrimination of amyloid protein misfolds and thereby for improved early-stage detection of Alzheimer’s and Parkinson’s diseases. With the methodological setup to be developed here, we will be able to contribute to the rational design of improved fluorescent amyloid biomarkers. In both spectroscopic fields, we will work in close collaboration with experimental colleagues.