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

光谱技术已成为自然科学许多分支中不可或缺的工具。在原子水平上对光谱结果的解释依赖于计算辅助。因此，计算光谱方法是实验不可缺少的补充。然而，今天的理论光谱学方法受到生物分子系统的大尺寸和此类应用所需精度的挑战。对于电子光谱学，所谓的多尺度方法已被证明非常成功。多尺度方法背后的哲学是将计算工作集中在大型系统的某些方面，从而为感兴趣的科学问题定制计算设置。例如，这可能是嵌入蛋白质中的发色团的局部激发。其余部分以更近似的方式处理。对于振动波函数方法，多尺度方法目前几乎没有发展。然而，它们具有巨大的潜力，可以加速大分子系统振动光谱的发现。这一潜力将在本研究计划中加以利用。在多尺度振动波函数方法的发展中，电子多尺度和碎裂方法也将是必不可少的，因为精确的电子势能面是这些计算的先决条件。此外，该计划将解决发射光谱学的多尺度方法中存在的一些挑战。所开发的方法将成为未来生物分子系统理论光谱学的宝贵工具。在这项研究计划中，我们将阐明振动和荧光光谱学中的以下挑战性问题。(i)我们如何将氢键系统和蛋白质的构象和局部结构变化精确地映射到一维和二维红外光谱？(ii)通过荧光寡聚噻吩生物标记物区分不同淀粉样纤维的原子机制是什么？点（i）是根本的兴趣：蛋白质构象的详细知识是必不可少的了解他们的功能和氢键往往发挥关键作用。点（ii）的目标系统，淀粉样蛋白原纤维的荧光生物标志物，是有前途的候选人的光谱歧视的淀粉样蛋白错误折叠，从而改善早期检测阿尔茨海默氏症和帕金森氏症。随着这里开发的方法学设置，我们将能够为改进的荧光淀粉样蛋白生物标志物的合理设计做出贡献。在这两个光谱领域，我们将与实验同事密切合作。

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.