Vibrational Exciton Models for Biomolecules from Quantum Chemistry

振动光谱学可以提供对蛋白质折叠过程中以及无序或未折叠蛋白质中发生的快速过程的见解。在这里，我们提出了有效的计算方法可靠地预测振动光谱的生物分子系统，特别是二维红外（2D-IR）和振动拉曼光学活性（罗阿）光谱的构象灵活的多肽和蛋白质的发展。为此，我们将开发振动激子模型，直接从量子化学计算的多肽和蛋白质通过采用严格定义的本地化模式，提供了这样的计算和振动激子模型之间的直接连接。特别是，我们提出了一种新的方法来开发振动激子模型，超越了目前的最先进的结合以下想法：（1）而不是依赖于（过度）简化的模型系统，如N-甲基乙酰胺和甘氨酸二肽的计算，我们的新的振动激子模型的参数将来自较大的多肽模型的二级结构元素的计算。(2)为了将我们的振动激子模型应用于2D-IR光谱，我们将在此参数化中包括局域模式的非谐性，而不是依赖于目前使用的经验参数。(3)虽然振动激子模型到目前为止已经集中在IR和2D-IR光谱，我们建议也开发振动激子模型的手性振动光谱，特别是罗阿光谱。(4)我们的目标是开发通用协议，适用于任何类型的分子中的振动与重复的积木，而目前的协议参数化的振动激子模型大多局限于酰胺I vibrations.In本项目中，我们将应用开发的协议来研究扩展酰胺III区域的结构灵敏度在罗阿和二维红外光谱。对于罗阿光谱，这将允许现有的实验的解释，而2D-IR光谱，它将把我们的位置，提出和激发新的实验，在扩展酰胺III区。

Vibrational spectroscopy can provide insights into fast processes occurring during protein folding and in disordered or unfolded proteins. Here, we propose the development of efficient computational methods for reliably predicting vibrational spectra of biomolecular systems, in particular for two-dimensional infrared (2D-IR) and vibrational Raman optical activity (ROA) spectroscopy of conformationally flexible polypeptides and proteins. To this end, we will develop vibrational exciton models that are derived directly from quantum-chemical calculations on polypeptides and proteins by employing rigorously-defined localized modes, which provide a direct connection between such calculations and vibrational exciton models. In particular, we propose a new methodology for developing vibrational exciton models that goes beyond the present state-of-the art by combining the following ideas: (1) Instead of relying on calculations for (over-)simplified model systems such as N-methylacetamid and glycine dipeptide, the parameters of our novel vibrational exciton models will be derived from calculations on larger polypeptide models of secondary structure elements. (2) For applying our vibrational exciton models to 2D-IR spectroscopy, we will include the anharmonicities of the localized modes in this parametrization instead of relying on the empirical parameters currently in use. (3) While vibrational exciton models have so far been focussed on IR and 2D-IR spectroscopy, we propose to also develop vibrational exciton models for chiral vibrational spectroscopies, in particular for ROA spectroscopy. (4) We aim at developing general protocols that are applicable for any kind of vibration in molecules with repeating building blocks, whereas the current protocols for parametrizing vibrational exciton models are mostly restricted to the amide I vibrations.In the present project, we will apply the developed protocols to study the structural sensitivity of the extended amide III region in both ROA and 2D-IR spectroscopy. For ROA spectroscopy, this will allow for an interpretation of existing experiments, whereas for 2D-IR spectroscopy it will put us in the position to propose and inspire new experiments looking at the extended amide III region.